Forum 34

Table of Contents*
PHARMACOPEIAL FORUM VOL. 34 NO. 5 SEPT.OCT. 2008
STANDARDS DEVELOPMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HOW TO USE PF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section Descriptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Committee Designations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Staff Directory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . POLICIES AND ANNOUNCEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . USP Proposes Changes to General Chapter h711i Dissolution; Requirements for the Salicylic Acid Dissolution Calibrator to Be Discontinued . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stimuli Article Proposes Changes to Heavy Metals/Inorganic Impurities General Chapter . . . . . . . . . . . . . . . . . . . . Use of USP Website . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Residual Solvents: General Notices and General Chapter h467iOfcial July 1, 2008 . . . . . . . . . . . . . . . . . . . . . . Pharmacopeial Forum Public Review and Comment Period Deadlines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Priority New Monograph Items . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INTERIM REVISION ANNOUNCEMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MONOGRAPHS (USP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bupropion Hydrochloride Extended-Release Tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Carvedilol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Carvedilol Tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dactinomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Fexofenadine Hydrochloride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nifedipine Extended-Release Tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GENERAL TEST CHAPTERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h11i USP Reference Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ERRATA LIST FOR USP 31NF 26 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IN-PROCESS REVISION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MONOGRAPHS (USP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acetaminophen (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amifostine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amlodipine Besylate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amlodipine Besylate Tablets [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ampicillin (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Aspirin (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Azithromycin Tablets [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Benzocaine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Benzoic Acid (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bicalutamide Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bleomycin for Injection (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Caffeine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chloral Hydrate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Anhydrous Citric Acid (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Citric Acid Monohydrate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cocaine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cocaine Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Codeine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Codeine Sulfate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dantrolene Sodium Capsules (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dicyclomine Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dopamine Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Doxazosin Mesylate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ecamsule Solution [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Erythromycin Pledgets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sterile Erythromycin Ethylsuccinate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1093 1097 1098 1101 1103 1107 1108 1108 1108 1108 1108 1109 1119 1123 1123 1124 1126 1127 1127 1127 1130 1130 1131 1133 1136 1136 1136 1136 1137 1140 1143 1143 1147 1147 1147 1150 1150 1150 1150 1151 1151 1151 1151 1151 1151 1152 1152 1152 1153 1157 1158
* The USPNF (USP 31NF 26), the Supplement (Supp), or the Interim Revision Announcement (IRA) for which the revision proposal is targeted is shown in parentheses next to each proposed item.
1090
Contents*
Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

1158 1158 1163 1163 1164 1164 1164 1164 1168 1170 1173 1176 1177 1179 1179 1179 1179 1179 1179 1180 1180 1180 1182 1183 1186 1189 1192 1193 1193 1193 1197 1197 1197 1200 1205 1207 1207 1209 1209 1209 1211 1211 1217 1217 1218 1220 1222 1223 1224 1224 1226 1227 1228 1230 1230 1232 1238 1241 1243 1251 1252
Famotidine for Oral Suspension (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Glyburide and Metformin Hydrochloride Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Halazone (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Imipramine Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Irbesartan (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lactic Acid (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Losartan Potassium Tablets [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mesna [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Moxioxacin Hydrochloride [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Moxioxacin Ophthalmic Solution [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Niacinamide (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oxcarbazepine [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pamidronate Disodium (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physostigmine (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physostigmine Salicylate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physostigmine Sulfate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pilocarpine Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pilocarpine Nitrate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Potassium Bitartrate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pralidoxime Chloride for Injection (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pravastatin Sodium Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quinapril Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risedronate Sodium [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risedronate Sodium Tablets [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sertraline Hydrochloride [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sodium Sulfate (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spectinomycin for Injectable Suspension (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Streptomycin Injection (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tamsulosin Hydrochloride Capsules [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Terbinane Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Thimerosal (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Topiramate Tablets [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tramadol Hydrochloride (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tylosin Injection (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DIETARY SUPPLEMENTSMONOGRAPHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Fish Oil Containing Omega-3 Acids (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hawthorn Leaf with Flower (Proposal for IRA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Powdered Hawthorn Leaf with Flower (Proposal for IRA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alpha Lipoic Acid (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . EXCIPIENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Excipients, USP and NF Excipients, Listed by Category (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . MONOGRAPHS (NF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Behenoyl Polyoxylglycerides [New] (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Silicied Microcrystalline Cellulose [New] (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Corn Oil (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cottonseed Oil (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ethyl Acetate (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ethyl Maltol [New] (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lauroyl Polyoxylglycerides (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methyl Alcohol (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hydrogenated Polydecene (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stearoyl Polyoxylglycerides (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GENERAL TEST CHAPTERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h11i USP Reference Standards (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h467i Residual Solvents (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h621i Chromatography (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h643i Total Organic Carbon (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h711i Dissolution (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h785i Osmolality and Osmolarity (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h853i Fluorescence Spectroscopy [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
# 2008 The United States Pharmacopeial Convention All Rights Reserved.
Contents*
1091
1266 1282 1290 1297 1297 1319 1319 1319 1319 1320 1320 1322 1323 1337 1339 1341 1343
h854i Mid-Infrared Spectroscopy [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h857i Ultraviolet-Visible Spectroscopy [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h905i Uniformity of Dosage Units (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GENERAL INFORMATION CHAPTERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h1235i Vaccines for Human UseGeneral Considerations [New] (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . REAGENTS, INDICATORS, AND SOLUTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reagent Specications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sodium 1-Decanesulfonate [New] (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methylbenzothiazolone Hydrazone Hydrochloride (2nd Supp to NF 27) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCE TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Container Specications for Capsules and Tablets (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Description and Solubility (2nd Supp to USP 32) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PREVIOUS PF PROPOSALS STILL PENDING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CANCELED PROPOSALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HARMONIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . STIMULI TO THE REVISION PROCESS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Instructions to Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Correction: The Inhalation Ad Hoc Advisory Panel for the USP Performance Tests of Inhalation Dosage Forms, Vivian A. Gray (Co-Chair), Anthony J. Hickey, PhD, DSc (Co-Chair), Patrick Balmer, PhD, Neal M. Davies, PhD, RPh, Craig Dunbar, PhD, Thomas S. Foster, PharmD (Chair, Biopharmaceutics Expert Committee), Bo L. Olsson, PhD, Masahiro Sakagami, PhD, Vinod P. Shah, PhD (Scientic Liaison), Michael J. Smurthwaite, BSc, John M. Veranth, PhD, Kahkashan Zaidi, PhD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Chapter on Inorganic Impurities: Heavy Metals, USPAd Hoc Advisory Panel on Inorganic Impurities and Heavy Metals and USP Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Cadaver Skin Absorption Model and the Drug Development Process, Thomas J. Franz, MS, MD, Paul A. Lehman, MS, Sam G. Raney, PhD, PRACS Institute, Ltd.Cetero Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NOMENCLATURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1344 1345 1349 1357 1359
# 2008
The United States Pharmacopeial Convention
All Rights Reserved.
HOW TO USE PF
1103
STAFF DIRECTORY This updated directory reects assignment changes based on 20052010 Expert Committees. The general USP telephone number, (301) 881-0666, may still be used for general inquiries or when a particular Expert Committee is not identied. The fax number is (301) 816-8373.
STAFF Darrell Abernethy Chief Science Ofcer Clydewyn M. Anthony, Ph.D., Scientist Fouad Atouf, Ph.D., Senior Scientic Associate Shawn C. Becker, M.S., B.S.N., R.N., Director, Patient Safety Initiatives Daniel K. Bempong, Ph.D., Senior Scientist Kristie Bowman, Senior Scientic Associate William E. Brown, Senior Scientist Damian A. Cairatti, Senior Scientist Larry N. Callahan, Ph.D., Senior Scientist Todd L. Cecil, Ph.D., Vice President, Compendial Sciences Diane Cousins, R.Ph., Vice President, Healthcare Quality and Information Behnam Davani, Ph.D., Senior Scientist Anthony DeStefano, Vice President, General Chapters Ian F. DeVeau, Ph.D., Director, Veterinary Drugs and Radiopharmaceuticals Lawrence Evans III, Ph.D., M P.H., Senior Scientist Gabriel I. Giancaspro, Ph.D., Director, Dietary Supplements Brian D. Gilbert, Ph.D., Scientist Elena Gonikberg, Ph.D., Senior Scientist James Grifths, Vice President, Food and Dietary Supplement Standards Antonio Hernandez-Cardoso, Scientist, Latin American Specialist
# 2008
E-MAIL dra@usp.org cma@usp.org
PHONE (301) 816-8184 (301) 816-8139
ASSIGNMENT
Monograph Development Cough, Cold, and Analgesics (MD-CCA) B&B Cell, Gene, and Tissue Therapies (BB CGT)
fa@usp.org scb@usp.org dkb@usp.org kxb@usp.org web@usp.org
(301) 816-8365 (301) 816-8216 (301) 816-8143 (301) 816-8462 (301) 816-8380
Pulmonary and Steroids (MD-PS) Food Ingredients (FI) Biopharmaceutics (BPC); Pharmaceutical Dosage Forms (PDF) USPNF Spanish Edition B&B Proteins and Polysaccharides (BB PP)
dac@usp.org lnc@usp.org tlc@usp.org ddc@usp.org
(301) 816-8307 (301) 816-8385 (301) 816-8234 (301) 816-8215
bd@usp.org
(301) 816-8394
Monograph Development Antivirals and Antimicrobials (MD-AA)
ajd@usp.org ifd@usp.org
(301) 998-6303 (301) 816-8178 Veterinary Drugs (VET)
le@usp.org gig@usp.org
(301) 816-8389 (301) 816-8343
Dietary SupplementsNonBotanicals (DSN)
bg@usp.org eg@usp.org
(301) 816-8223 (301) 816-8251 Monograph Development Gastrointestinal, Renal, and Endocrine (MD-GRE)
jg@usp.org
(301) 998-6811
ahc@usp.org
(301) 816-8308
USP Spanish Edition; General Chapters (GC)
1104
HOW TO USE PF
STAFF DIRECTORY (continued)
STAFF Desmond G. Hunt, Ph.D., Scientist
E-MAIL dgh@usp.org
PHONE (301) 816-8341
ASSIGNMENT Packaging and Storage (P&S); Parenteral Products Industrial (PPI) Dietary Supplements Performance Standards (DS-PS) Excipient Monographs 1 (EM1); Excipient General Chapters (EGC)
How to Use PF
Ping Jin, Ph.D., Senior Scientic Associate Robert Lafaver, Scientist Angela G. Long, Vice President, Volunteer and Organizational Affairs and Executive Secretariat Victor Xiaobin Lu, Ph.D., Senior Scientist Feiwen Mao, Scientist Margareth R. Marques, Ph.D., Senior Scientist and Latin American Liaison Marcia D. Mayeld, Manager, Monograph Development Jeff Moore, Ph.D., Senior Scientic Associate Kevin Moore, Ph.D., Scientist Tina S. Morris, Ph.D., Director, Biologics and Biotechnology Amy Neal, DVM, Senior Scientist Claudia C. Okeke, Ph.D., Scientic Fellow, Patient Safety Horacio Pappa, Ph.D., Senior Scientist and Latin American Liaison Denise Penn, R.Ph., Senior Drug Information Specialist Deborah G. Perfetto, Pharm.D., Director, Healthcare Information Morgan Puderbaugh, Scientic Associate Sujatha Ramakrishna, Ph.D., Scientist Hariram Ramanathan, Scientic Associate Ravi Ravichandran, Ph.D., Senior Scientist Gary E. Ritchie, M.S., Scientic Fellow for PAT
pj@usp.org rhl@usp.org agl@usp.org
(301) 998-6827 (301) 816-8335 (301) 816-8382
vxl@usp.org fm@usp.org
(301) 816-8336 (301) 816-8320
B&B Vaccines and Virology (BB-VV) Monograph Development Ophthalmology, Oncology, and Dermatology (MD-OOD) Biopharmaceutics (BPC); Pharmaceutical Dosage Forms (PDF); Reagents
mrm@usp.org
(301) 816-8106
mxm@usp.org jm@usp.org ktm@usp.org tsm@usp.org
(301) 816-8358 (301)816-8288 (301)816-8369 (301) 816-8397 Food Ingredients (FI) Harmonization; Monograph Improvement
an@usp.org cco@usp.org
(301) 998-6786 (301) 816-8243
Veterinary Medicine Information (VMI) Sterile Compounding (SCC)
hp@usp.org
(301) 816-8319
General Chapters (GC); Statistics (STAT) Drug Information
dsp@usp.org dgp@usp.org mxp@usp.org sxr@usp.org hr@usp.org rr@usp.org
(301) 816-8392 (301) 816-8317 (301) 998-6833 (301) 816-8349 (301) 816-8313 (301) 816-8330
Monograph Development Cardiovascular (MD-CV)
Monograph Development Psychiatrics and Psychoactives (MD-PP) General Chapters (GC); Pharmaceutical Waters (PW); Statistics (STAT)
ger@usp.org
(301) 816-8353
# 2008
HOW TO USE PF
1105
STAFF DIRECTORY (continued)
STAFF Karen A. Russo, Ph.D., Director, Small Molecules and Monograph Acquisition Leonel Santos, Ph.D., Senior Scientist Dandapantula Sarma, Ph.D, Senior Scientist Rick Schnatz, Pharm.D, Manager Stefan P. Schuber, Ph.D., Director, Scientic Reports Maged H. M. Sharaf, Ph.D., Senior Scientist Catherine M. Sheehan, Director, Excipients and Food Ingredients Tom Sigambris, M.S., Scientist Nora R. Suarez, Scientic Associate Anita Y. Szajek, Ph.D., Senior Scientist Radhakrishna S. Tirumalai, Ph.D., Senior Scientist
E-MAIL kar@usp.org
PHONE (301) 816-8379
ASSIGNMENT
lxs@usp.org dns@usp.org rxs@usp.org sps@usp.org mhs@usp.org cxs@usp.org
(301) 816-8168 (301) 816-8354 (301) 816-8526 (301) 816-8551 (301) 816-8318 (301) 816-8262
International Health (IH) How to Use PF Dietary Supplements Information (DSI) Compounding Pharmacy (CRX)
Dietary Supplements Botanicals (DSB) Food Additives (FA)
tzs@usp.org nrs@usp.org aey@usp.org rst@usp.org
(301) 998-6789 (301) 816-8326 (301) 816-8325 (301) 816-8339 B&B Blood and Blood Products (BB BBP) General Toxicity and Medical Device Biocompatibility (GTMDB); Microbiology and Sterility Assurance (MSA) Dietary Supplements General Chapters (DS-GC)
Yoshiyuki Tokiwa, Ph.D., Senior Scientist Domenick Vicchio, Senior Scientist Hong Wang, Ph.D., Scientist Andrzej Wilk, Ph.D., Sr. Scientist Ahalya Wise, Scientist Kahkashan Zaidi, Ph.D., Senior Scientist
yt@usp.org dwv@usp.org hw@usp.org
(301) 816-8321 (301) 998-6828 (301) 816-8351
Excipient Monographs 2 (EM2); Excipient General Chapters (EGC) Nomenclature (NOM) Monograph Development Antibiotics (MD-ANT) Aerosols (AER); General Chapters (GC)
aw@usp.org aww@usp.org kxz@usp.org
(301) 816-8305 (301) 816-8607 (301) 816-8269
# 2008
1108
POLICIES AND ANNOUNCEMENTS
USP PROPOSES CHANGES TO GENERAL CHAPTER h711i DISSOLUTION; REQUIREMENTS FOR THE SALICYLIC ACID DISSOLUTION CALIBRATOR TO BE DISCONTINUED. The Biopharmaceutics Expert Committee (BPC EC) has approved the deletion of the use of USP Salicylic Acid Tablets RS from the Performance Verication Test (PVT) for test assemblies using USP Apparatus 1 (Basket Apparatus) and Apparatus 2 (Paddle Apparatus). The deletion of USP Salicylic Acid Tablets RS from Dissolution h711i has an intended implementation date of December 1, 2009, the ofcial date of the Second Supplement to USP 32. This change is presented as an InProcess Revision to allow considerable advance notice for affected parties. In addition, starting with USP Prednisone Tablets RS, Lot Q, the results of the PVT for Apparatus 1 and 2 will be evaluated based on the mean (trueness) and standard deviation (precision) of the data generated. USP will provide a calculation spreadsheet in the Compendial Tools area of the website to assist with these calculations. Please direct any questions to William Brown, Senior Scientist (301-816-8380 or web@usp.org) or Anthony DeStefano, Ph.D. (301-998-6303 or ajd@usp.org). STIMULI ARTICLE PROPOSES CHANGES TO H E AV Y M E TA L S / I N O R G A N I C I M P U R I T I E S GENERAL CHAPTER. Many toxic metal impurities found in pharmaceutical articles have been controlled for years by application of the test for Heavy Metals described in USPNF General Chapter Heavy Metals h231i. However, the procedures and the methods contained in h231i lack the sensitivity, specicity, and recovery to monitor properly the levels of these metals. A number of additional chapters for the control of specic metals and other inorganic impurities are contained in USPNF. This Stimuli article proposes a new USP General Chapter for the control of inorganic impurities in drug and dietary supplement articles intended for use in humans. The proposed new General Chapter recommends procedures that rely on modern analytical technology and includes limits that are based on toxicity and exposure levels for the selected metals. The new General Chapter also introduces a performance-based approach for the selection of the appropriate technology. This chapter, proposed to replace General Chapter h231i may have an impact on other General Chapters that control metals. Contact Kahkashan Zaidi, Ph.D., Senior Scientist, Documentary Standards Division (301-816-8269 or kxz@usp.org) USE OF USP WEBSITE. USP is relocating to the www.usp.org website information formerly published in PF . USP is undertaking this initiative to assure that all interested parties have access to this information. USP understands the information it publishes is critical to industry operations and
needs to be broadly communicated to stakeholders in a timely manner. Because the website is available to everyone and is routinely maintained, it is the ideal vehicle for USP to use in order to achieve this goal. The following information, previously published in the Policies and Announcements section of the Pharmacopeial Forum, is now accessible on USPs website. IRA Commentary Compendial Notices Pharmacopeial Education Courses Other important information that resides on the USP website includes: Rules and Procedures of the Council of Experts Revision Bulletins Postponements Intent to Revise Letters Explanatory Notes and Announcements Errata Announcements Stimuli to the Revision Process Articles Reference Standards Catalog The USP intends to continue this effort and is targeting the following information to be posted only to the USP website in the near future: Reference Standards Abeyance List High Priority Monograph List USP encourages stakeholders to sign up for the Compendial Notices e-mail service in order to receive notices of new postings to the USP website. To sign up for this service, go to http://www.usp.org/support/products/uspNewslettersRequest.html?promo=compendial. RESIDUAL SOLVENTS: GENERAL NOTICES AND GENERAL CHAPTER h467iOFFICIAL JULY 1, 2008.The USP Residual Solvent requirements in the General Notices becomes ofcial July 1, 2008. As a result, the title of General Chapter h467i is now Residual Solvents instead of Organic Volatile Impurities, and references to Organic Volatile Impurities are deleted from monographs. Please direct any questions to Horacio Pappa, Ph.D., Senior Scientist (301-816-8319 or hp@usp.org). PHARMACOPEIAL FORUM PUBLIC REVIEW AND COMMENT PERIOD DEADLINES. The USP welcomes and encourages interested parties to submit comments and data regarding potential, proposed, or adopted (ofcial) standards. In accordance with the Rules and Procedures of the 20052010 Council of Experts, USP has implemented a 90-day comment period by providing a deadline for each issue of PF unless otherwise stated in the individual Brieng. The listing of comment period deadlines and the targeted ofcial publications are listed on the next page. Look for upcoming educational opportunities on the topic of Heavy Metals: www.usp.org/education.
Policies and Announcements
# 2008
1109
Pharmacopeial Forum PF 34(2) PF 34(3) PF 34(4) PF 34(5) PF 34(6) PF 35(1)
Comment Deadline June 15, 2008 August 15, 2008 October 15, 2008 December 15, 2008 February 15, 2009 April 15, 2009
Targeted Ofcial Publication USP 32NF 27 1st Supplement USP 32NF 27 2nd Supplement USP 33NF 28
Publication Date February 2009 June 2009 November 2009
Ofcial Date August 2009 December 2009 May 2010
All ofcial revisions are published in the annual edition or Supplements to USPNF (twice yearly). Between these publications, ofcial revisions are published in PF in the Interim Revision Announcement section; these revisions are also incorporated in the upcoming Supplement. The ofcial publication in which an IRA is incorporated will depend upon publication deadlines. The IRAs appearing in PF Numbers 5 and 6 of each
volume will not appear until Supplement 1. See the table below. The electronic version of USPNF is updated as each Supplement becomes available and, therefore, contains all ofcial text up to and including the contents of the latest Supplement. The table below outlines the publications and their release and ofcial dates, and the book or Supplement that supersedes them.
Publication Schedules
Publication USP 31NF 26 IRA [PF 34(1)] 1st Supplement to USP 31NF 26 IRA [PF 34(2)] IRA [PF 34(3)] 2nd Supplement to USP 31NF 26 IRA [PF 34(4)] IRA [PF 34(5)] IRA [PF 34(6)] Release Date Nov. 1. 2007 Jan. 1, 2008 Feb. 1, 2008 Mar. 1, 2008 May 1, 2008 June 1, 2008 July 1, 2008 Sept. 1, 2008 Nov. 1, 2008 Ofcial Date May 1, 2008 Feb. 1, 2008 Aug. 1, 2008 Apr. 1, 2008 June 1, 2008 Dec. 1, 2008 Aug. 1, 2008 Oct. 1, 2008 Dec. 1, 2008 Superseded by 1st Supplement to USP 31NF 26 2nd Supplement to USP 31NF 26 2nd Supplement to USP 31NF 26 2nd Supplement to USP 31NF 26 USP 32NF 27 USP 32NF 27 1st Supplement to USP 32NF 27 1st Supplement to USP 32NF 27 2nd Supplement to USP 32NF 27
PRIORITY NEW MONOGRAPH ITEMS. USP is seeking monographs for the following drug substances and drug products that are or soon will be off patent and thus are of the highest priority. USP also is seeking monographs for the excipients listed below. Monographs are marked received upon receipt of the monograph proposal. Received monographs are removed from this list upon publication in Pharmacopeial Forum or when posted in the Pending Monographs section of the USP website (http://www.usp.org/standards/pending/).
(This list has been updated as of June 20, 2008.) For the most current list, please consult the Priority New Monograph Items List posted at http://www.usp.org/USPNF/submitMonograph/ newMon.html. Monograph sponsors should consult USPs Guideline for Submitting Requests for Revision to the USPNF posted at http:// www.usp.org/USPNF/submitMonograph/subGuide.html. For additional information, contact Karen A. Russo, Ph.D., kar@usp.org.
Small Molecules (Drug Substances)As of June 20, 2008 1. Allopurinol Sodium 4. Anagrelide Hydrochloride (Received) 7. Azelaic Acid (Received) 10. Benzphetamine Hydrochloride 13. Calcium Trisodium Pentetate 16. Carmustine (Received) 19. Ceftiofur Hydrochloride (Received)
# 2008
2. Aminopropazine Fumarate 5. Arsenic Trioxide 8. Balsalazide Disodium 11. Bivalirudin (Received) 14. Calfactant 17. Cefditoren Pivoxil (Received) 20. Cetrorelix
3. Aminopterin Sodium 6. Auranfoin 9. Bentoquatam 12. Calcipotriene 15. Candesartan Cilexetil (Received) 18. Ceftibuten 21. Cevimeline
1110
Small Molecules (Drug Substances)As of June 20, 2008 (Continued) 22. Chloroxine 25. Cytarabine Liposome 28. Desirudin 31. Dextromethorphan Polistirex 34. Entacapone 37. Erythromycin Thiocyanate 40. Estramustine Phosphate Sodium 43. Etoposide Phosphate 46. Felbamate 49. Gadobenate Dimeglumine 52. Ganirelix 55. Halobetasol Propionate (Received) 58. Ibandronate Sodium 61. Irinotecan Hydrochloride (Received) 64. Latanoprost (Received) 67. Metipranolol Hydrochloride 70. Milrinone Lactate 73. Nalbuphine Hydrochloride 76. Nedocromil Sodium 79. Nisoldipine 82. Oxcarbazepine (Received) 85. Pentamidine Isethionate (Received) 88. Pirbuterol Acetate (Received) 91. Pramiprexole Dihydrochloride 94. Rivastigmine Tartrate (Received) 97. Rosiglitazone Maleate 100. Sibutramine Hydrochloride (Received) 103. Spectinomycin Sulfate 106. Tenofovir Disoproxil Fumarate (Received) 109. Tiopronin 112. Trimetrexate Glucuronate 115. Zaleplon 118. Zonisamide 23. Choline Salicylate 26. Dalfopristin 29. Desonide (Received) 32. Difenoxin Hydrochloride 35. Epoprostenol Sodium 38. Esmolol Hydrochloride 41. Ethanolamine Oleate 44. Exemestane 47. Fluoromethane F 18 50. Gadopentetic Acid 53. Glyceryl Aminobenzoate 56. Haloperidol Decanoate (Received) 59. Imipramine Pamoate 62. Isosulfan Blue 65. Lomustine (Received) 68. Midazolam (Received) 71. Misoprostol (Received) 74. Nalmefene Hydrochloride 77. Nicardipine Hydrochloride 80. Olsalazine Sodium (Received) 83. Oxiconazole Nitrate 86. Pioglitazone Hydrochloride 89. Poractant Alpha 92. Quetiapine Fumarate (Received) 95. Ropinirole Hydrochloride 98. Salmeterol Xinafoate (Received) 101. Sodium Phenylbutyrate 104. Streptozocin 107. Terconazole (Received) 110. Tranexamic Acid (Received) 113. Venlafaxine Hydrochloride (Received) 116. Zinc Tridosium Pentetate 24. Cysteamine Bitartrate 27. Dapirazole Hydrochloride 30. Dexrazoxane 33. Dioxacin Hydrochloride 36. Erythromycin Phosphate 39. Estazolam (Received) 42. Etomidate (Received) 45. Famciclovir 48. Fosfomycin Tromethamine (Received) 51. Gallium Nitrate 54. Guanidine Hydrochloride 57. Hydrocodone Polistirex 60. Imiquimod 63. Itraconazole (Received) 66. Lopinavir (Received) 69. Miglitol 72. Moexipril Hydrochloride 75. Nateglinide (Received) 78. Nilutamide 81. Orlistat (Received) 84. Pemirolast Potassium 87. Piperonyl Butoxide 90. Pormer Sodium 93. Ranitidine 96. Rose Bengal Disodium 99. Sertraline Hydrochloride (Received) 102. Sodium Phosphates 105. Tacrolimus (Received) 108. Tiludronate Disodium 111. Tranylcypromine Sulfate (Received) 114. Voriconazole (Received) 117. Zoledronic Acid
# 2008

Small Molecules (Drug Products)As of June 20, 2008
1111
1. Abacavir Sulfate, Lamivudine, and Zidovudine Tablets 4. Acetaminophen, Clemastine Fumarate and Pseudoephedrine Hydrochloride Tablets 7. Albuterol and Ipratropium Bromide Inhalation Solution 10. Albuterol Sulfate Inhalation Solution 13. Alfuzosin Extended-Release Tablets 16. Alprostadil Urethral Supository 19. Aminopropazine Fumarate Tablets 22. Amlodipine and Benazepril Hydrochloride Capsules 25. Arsenic Trioxide Injection 28. Auranon Capsules 31. Azithromycin for Injection (Received) 34. Balsalazide Disodium Capsules 37. Benazepril Hydrochloride and Hydrochlorothiazide Tablets 40. Benzocaine and Menthol Lotion 43. Brompheniramine Maleate, Dextromethorphan Hydrobromide and Pseudoephedrine Hydrochloride Oral Solution 46. Buprenorphine Hydrochloride Injection 49. Cabergoline Tablets (Received) 52. Calcipotriene Topical Solution 55. Calcium Acetate Capsules 58. Carbidopa and Levodopa Extended-Release Tablets (Received) 61. Carmustine For Injection (Received) 64. Cefditoren Pivoxil Tablets 67. Ceftiofur Hydrochloride Oral Suspension 70. Cevimeline Hydrochloride Capsules 73. Choline and Magnesium Salicylates Oral Solution 76. Ciclopirox Shampoo 79. Cimetidine Oral Solution 82. Ciprooxacin Otic Solution 85. Citric Acid, Gluconolactone, and Magnesium Carbonate Irrigation 88. Clobetasol Propionate Gel 91. Clotrimazole and Betamethasone Dipropionate Lotion 94. Conjugated Estrogens and Medroxyprogesterone Acetate Tablets 97. Cyclosporine Ointment 100. Cytarabine Liposome Injection 103. Dapiprazole for Ophthalmic Solution 106. Dexrazoxane for Injection
2. Acarbose Tablets 5. Acetazolamide Extended-Release Capsules 8. Albuterol Extended-Release Tablets 11. Albuterol Sulfate Oral Solution 14. Allopurinol for Injection 17. Aminopropazine Fumarate and Neomycin Sulfate Tablets 20. Aminopterin Sodium Tablets 23. Amphotericin B Injection 26. Atovaquone and Proguanil Hydrochloride Tablets 29. Azatadine Maleate and Pseudoephedrine Sulfate Extended-Release Tablets 32. Azithromycin Tablets (Received) 35. Beclomethasone Dipropionate Inhalation Aerosol 38. Bentoquatam Topical Suspension 41. Benzphetamine Hydrochloride Tablets 44. Budesonide Inhalation Aerosol 47. Butalbital and Acetaminophen Capsules 50. Calcipotriene Cream 53. Calcitriol Capsules 56. Calcium Trisodium Pentetate Injection 59. Carbidopa and Levodopa Tablets For Oral Suspension (Received) 62. Carmustine Implant 65. Ceftibuten Capsules 68. Cetirizine Hydrochloride Tablets (Received) 71. Chloroxine Cream 74. Choline and Magnesium Salicylates Tablets 77. Ciclopirox Topical Gel 80. Ciprooxacin Extended-Release Tablets 83. Cisplatin Injection 86. Cladribine Injection 89. Clorazepate Dipotassium Capsules 92. Compound Undecylenic Acid Cream 95. Cyclosporine Modied Capsules 98. Cyclosporine Topical Solution 101. Dalfopristin and Quinupristin Injection 104. Desirudin for Injection 107. Dextroamphetamine Sulfate ExtendedRelease Capsules
3. Acetaminophen, Butalbital, Caffeine, and Codeine Phosphate Capsules 6. Albuterol and Ipratropium Bromide Inhalation Aerosol 9. Albuterol Inhalation Aerosol 12. Alendronate Sodium Oral Solution 15. Alprazolam Extended-Release Tablets 18. Aminopropazine Fumarate Injection 21. Amiodarone Hydrochloride Injection 24. Anagrelide Hydrochloride Capsules (Received) 27. Atovaquone Tablets 30. Azelaic Acid Cream 33. Baclofen Injection Policies and Announcements 36. Beclomethasone Dipropionate Nasal Suspension 39. Benzocaine and Cetylpyridinium Chloride Lozenges 42. Bivalirudin Injection 45. Bupivacaine and Lidocaine Hydrochlorides Injection 48. Butalbital and Acetaminophen Tablets 51. Calcipotriene Ointment 54. Calcitriol Oral Solution 57. Calfactant Intratracheal Suspension 60. Carbidopa, Levidopa, and Entacapone Tablets 63. Cefdinir Tablets 66. Ceftibuten For Oral Suspension 69. Cetrorelix Injection 72. Chlorpromazine Hydrochloride Extended-Release Capsules 75. Choline Salicylate Oral Solution (Received) 78. Ciclopirox Topical Solution (Received) 81. Ciprooxacin Hydrochloride and Hydrocortisone Otic Suspension 84. Citalopram Hydrobromide Oral Solution 87. Clemastine Fumarate Syrup 90. Clorazepate Dipotassium Extended-Release Tablets 93. Compound Undecylenic Acid Topical Powder 96. Cyclosporine Modied Oral Solution 99. Cysteamine Bitartrate Capsules 102. Dantrolene Sodium Oral Suspension 105. Desonide Cream 108. Dextromethorphan Polistirex ExtendedRelease Oral Suspension
# 2008
1112
Small Molecules (Drug Products)As of June 20, 2008 (Continued) 109. Diazepam Injectable Emulsion 112. Difenoxin Hydrochloride and Atropine Sulfate Tablets 115. Diltiazem Hydrochloride Injection 118. Divalproex Sodium Delayed-Release Capsules 121. Doxepin Hydrochloride Cream 124. Edrophonium Chloride and Atropine Sulfate Injection 127. Entacapone Tablets (Received) 130. Epirubicin Hydrochloride Injection 133. Escitalopram Oxalate Tablets (Received) 136. Estazolam Tablets (Received) 139. Etidronate Disodium Injection Concentrate 142. Famotidine Orally Disintegrating Tablets 145. Fentanyl Lozenges 148. Ferrous Fumarate and Docusate Sodium Extended-Release Capsules 151. Flunisolide Inhalation Aerosol 154. Fluorescein Sodium Ophthalmic Solution 157. Fluticasone Propionate Inhalation Powder 160. Foscarnet Sodium Injection 163. Gadobenate Dimeglumine Injection 166. Ganirelix Acetate Injection 169. Gentamicin Sulfate Oral Solution 172. Granisetron Injection (Received) 175. Guaifenesin and Salts of Dextromethorphan and Pseudoephedrine Oral Solution 178. Halobetasol Propionate Ointment 181. Haloperidol Lactate Oral Concentrate 184. Hydrochlorothiazide Oral Solution 187. Hydrocodone Bitartrate and Aspirin Tablets 190. Hydrocortisone Acetate Dental Paste 193. Hydroumethiazide and Reserpine Tablets 196. Ibandronate Sodium Tablets 199. Imipramine Pamoate Capsules 202. Ipratropium Bromide Inhalation Solution 205. Isradipine Extended-Release Tablets 208. Ketoconazole Cream 211. Ketoprofen Extended-Release Capsules 214. Lactic Acid Lotion 217. Leucovorin Calcium for Injection 110. Diclofenac Sodium Ophthalmic Solution 113. Dioxacin Hydrochloride Tablets 116. Dinoprostone Vaginal Suppositories 119. Dorzolamide and Timolol Ophthalmic Solution 122. Doxycycline Oral Gel 125. Enalapril Maleate and Felodipine Extended-Release Tablets 128. Ephedrine Sulfate and Guaifenesin Tablets 131. Epoprostenol for Injection 134. Esmolol Hydrochloride Injection 137. Estramustine Phosphate Sodium Capsules 140. Etomidate Injection 143. Felbamate Oral Suspension 146. Famciclovir Tablets 149. Fluconazole Oral Suspension 152. Flunisolide Nasal Spray 155. Fluorometholone Ointment 158. Fluticasone Propionate Ointment (Received) 161. Fosfomycin for Oral Solution 164. Gallium Nitrate Injection 167. Gatioxacin Injection 170. Gentamicin Sulfate Soluble Powder 173. Granisetron Tablets (Received) 176. Guanidine Hydrochloride Tablets 179. Haloperidol Decanoate Injection 182. Hydralazine Hydrochloride and Hydrochlorothiazide Capsules 185. Hydrocodone Bitartrate and Acetaminophen Capsules 188. Hydrocodone Bitartrate and Guaifenesin Oral Solution 191. Hydrocortisone Acetate Rectal Foam Aerosol 194. Hydromorphone Hydrochloride Oral Solution (Received) 197. Ibuprofen Capsules 200. Imiquimod Topical Cream 203. Irinotecan Hydrochloride Injection 206. Itraconazole Injection 209. Ketoconazole Shampoo 212. Ketoprofen Tablets 215. Lamotrigine Tablets 218. Levetiracetam Tablets 111. Diethylpropion Hydrochloride Extended-Release Tablets 114. Dihydroergotamine Mesylate Metered Spray 117. Diphenhydramine Hydrochloride and Acetaminophen Tablets 120. Dorzolamide Ophthalmic Solution 123. Econazole Nitrate Cream 126. Enalaprilat Injection (Received) 129. Epirubicin Hydrochloride for Injection 132. Epoprostenol Injection 135. Esomeprazole Magnesium Capsules 138. Ethanolamine Oleate Injection 141. Exemestane Tablets 144. Felbamate Tablets 147. Fentanyl Transdermal System (Received) 150. Fluconazole Tablets (Received) 153. Fluocinolone Acetonide Shampoo 156. Fluticasone Propionate Cream (Received) 159. Fluticasone Propionate Pressurized Inhaler 162. Gabapentin Oral Solution 165. Ganciclovir Capsules 168. Gatioxacin Tablets 171. Glipizide Extended-Release Tablets 174. Guaifenesin and Pseudoephedrine Hydrochloride Extended-Release Tablets 177. Halobetasol Propionate Cream 180. Haloperidol Lactate Injection 183. Hydrochlorothiazide Capsules 186. Hydrocodone Bitartrate and Acetaminophen Oral Solution 189. Hydrocodone Bitartrate and Homatropine Methylbromide Syrup 192. Hydrocortisone Butyrate Lotion 195. Hydroquinone Lotion 198. Idarubicin Hydrochloride Injection 201. Ipratropium Bromide Inhalation Aerosol 204. Isosulfan Blue Injection 207. Itraconazole Oral Solution 210. Ketoprofen Capsules (Received) 213. Ketotifen Fumarate Ophthalmic Solution 216. Latanoprost Ophthalmic Solution 219. Levocabastine Ophthalmic Suspension
# 2008
1113
Small Molecules (Drug Products)As of June 20, 2008 (Continued) 220. Levooxacin Solution 223. Lomustine Capsules 226. Lopinavir Solution 229. Meoquine Hydrochloride Tablets 232. Mesoridazine Besylate Concentrate 235. Methadone Hydrochloride Oral Concentrate 238. Methyclothiazide and Deserpidine Tablets 241. Metronidazole Capsules (Received) 244. Metronidazole Hydrochloride for Injection 247. Midazolam Injection (Received) 250. Milrinone Injection 253. Moexipril Hydrochloride Tablets 256. Morphine Sulfate Oral Solution 259. Mycophenolate Mofetil Capsules 262. Nalbuphine Hydrochloride Injection 265. Naphazoline Hydrochloride and Pheniramine Maleate Ophthalmic Solution 268. Nedocromil Sodium Inhalation Aerosol 271. Nilutamide Tablets 274. Nitroglycerin Solution In Acrylic Adhesive 277. Ooxacin In Dextrose Injection 280. Ondansetron Tablets (Received) 283. Oxcarbazepine Suspension 286. Pamidronate Disodium Injection 289. Paroxetine Hydrochloride ExtendedRelease Tablets 292. Penicillin G Potassium Tablets for Oral Solution 295. Pentazocine Hydrochloride and Acetaminophen Tablets 298. Phentermine Resin Complex Capsules 301. Pilocarpine Hydrochloride Ophthalmic Gel 304. Piperonyl Butoxide and Pyrethrins Aerosol Foam 307. Pormer Sodium for Injection 310. Povidone-Iodine Gauze 313. Povidone-Iodine Vaginal Suppositories 316. Prochlorperazine Maleate ExtendedRelease Capsules 221. Lincomycin Hydrochloride and Spectinomycin Sulfate Soluble Powder 224. Lopinavir and Ritonavir Solution 227. Loratadine Orally-Disintegrating Tablets (Received) 230. Melphalan for Injection 233. Metaraminol Bitartrate Injection 236. Methocarbamol and Aspirin Tablets 239. Methylphenidate Hydochloride Chewable Tablets 242. Metronidazole Cream 245. Metronidazole Lotion 248. Mifepristone Tablets 251. Misoprostol Tablets (Received) 254. Molindone Hydrochloride Oral Solution 257. Morphine Sulfate Oral Solution Concentrate 260. Mycophenolate Mofetil Oral Solution 263. Nalmefene Hydrochloride Injection 266. Naproxen Sodium Extended-Release Tablets 269. Neomycin Sulfate Oral Powder 272. Nimodipine Capsules 275. Nitroglycerin Transdermal System 278. Ooxacin Injection 281. Orphenadrine Citrate Extended Release Tablets (Received) 284. Oxcarbazepine Tablets (Received) 287. Pantoprazole Sodium for Injection 290. Paroxetine Oral Suspension 293. Pentamidine Isethionate for Inhalation 296. Phendimetrazine Tartrate ExtendedRelease Capsules 299. Phenylephrine Hydrochloride and Chlorpheniramine Maleate Extended-Release Capsules 302. Pilocarpine Hydrochloride Ophthalmic Ointment 305. Pirbuterol Acetate Inhalation Aerosol 308. Povacrylate Solution 311. Povidone-Iodine Swabsticks 314. Pramipexole Dihydrochloride Tablets 317. Progesterone Capsules 222. Liothyronine Injection 225. Lopinavir Capsules 228. Losartan Potassium Tablets (Received) 231. Mesalamine Suppositories 234. Methacholine Chloride for Inhalation Solution 237. Methoxsalen Softgels 240. Metipranolol Ophthalmic Solution 243. Metronidazole Extended-Release Tablets 246. Miconazole Nitrate Topical Aerosol 249. Miglitol Tablets Policies and Announcements 252. Moexipril Hydrochloride and Hydrochlorothiazide Tablets 255. Morphine Sulfate for Injection Concentrate 258. Morphine Sulfate Tablets 261. Mycophenolate Mofetil Tablets 264. Naphazoline Hydrochloride and Pheniramine Maleate Ophthalmic Solution 267. Nateglinide Tablets (Received) 270. Nicardipine Hydrochloride Capsules 273. Nisoldipine Extended-Release Tablets 276. Nizatidine Tablets 279. Olsalazine Sodium Capsules 282. Orphenadrine Citrate, Aspirin, and Caffeine Tablets 285. Oxiconazole Cream 288. Pantoprazole Sodium Tablets 291. Pemirolast Potassium Ophthalmic Solution 294. Pentamidine Isethionate Injection (Received) 297. Phenobarbital Capsules 300. Phenylephrine Hydrochloride, Chlorpheniramine Maleate, and Acetaminophen Extended-Release Tabs 303. Pioglitazone Hydrochloride Tablets 306. Poractant Alpha Suspension 309. Povacrylate-Iodine Topical Solution 312. Povidone-Iodine Topical Aerosol Foam 315. Prednisolone Sodium Phosphate Oral Solution 318. Promethazine and Phenylephrine Hydrochlorides and Codeine Phosphate Syrup (Received)
# 2008
1114
Small Molecules (Drug Products)As of June 20, 2008 (Continued) 319. Promethazine and Phenylephrine Hydrochlorides Syrup (Received) 322. Propafenone Hydrochloride Tablets 325. Pseudoephedrine Hydrochloride, Chlorpheniramine Maleate, and Codeine Phosphate Oral Solution 328. Pseudoephedrine Sulfate and Dexbrompheniramine Maleate Oral Solution 331. Quinapril Hydrochloride and Hydrochlorothiazide Tablets 334. Ranitidine Capsules 337. Rimantadine Hydrochloride Oral Solution 340. Rivastigmine Tartrate Capsules (Received) 343. Ropinirole Hydrochloride Tablets 346. Salicylic Acid and Sulfur Lotion 349. Salicylic Acid Ointment 352. Scopolamine Transdermal System 355. Sibutramine Hydrochloride Capsules 358. Sodium Iodide Injection 361. Sodium Phosphates for Oral Suspension 364. Sterile Talc Aerosol 367. Sulconazole Nitrate Cream 370. Sulfasalazine Oral Suspension 373. Sumatriptan Tablets (Received) 376. Tacrolimus Ointment 379. Tenofovir Disoproxil Fumarate Tablets (Received) 382. Terbinane Hydrochloride Cream 385. Terconazole Vaginal Cream 388. Testosterone Transdermal System 391. Tioconazole Vaginal Ointment 394. Topiramate Capsules (Received) 397. Torsemide Tablets (Received) 400. Tranexamic Acid Injection 403. Tretinoin Microsphere Gel 406. Trimetrexate for Injection 409. Trolamine Salicylate Cream 412. Undecylenic Acid Topical Foam Aerosol 415. Venlafaxine Extended-Release Capsules (Received) 418. Verapamil Hydrochloride ExtendedRelease Capsules 320. Promethazine Hydrochloride and Codeine Phosphate Oral Solution (Received) 323. Pseudoephedrine Hydrochloride and Brompheniramine Maleate Extended-Release Tablets 326. Pseudoephedrine Hydrochloride, Guaifenesin, and Codeine Phosphate Oral Solution 329. Pseudoephedrine Sulfate, Dexbrompheniramine Maleate, and Acetaminophen Extended-Release Tablets 332. Quinidine Sulfate Injection 335. Rauwola Serpentina and Endroumethiazide Tablets 338. Risperidone Oral Solution (Received) 341. Rivastigmine Tartrate Oral Solution (Received) 344. Rosiglitazone Maleate Tablets 347. Salicylic Acid and Sulfur Shampoo 350. Salmeterol Inhalation Aerosol 353. Selegiline Hydrochloride Capsules 356. Sodium Bicarbonate and Sodium Citrate for Oral Solution 359. Sodium Phenylbutyrate Oral Powder 362. Sodium Phosphates Tablets 365. Streptozocin for Injection 368. Sulfacetamide Sodium and Fluorometholone Ophthalmic Suspension 371. Sulisobenzone Lotion 374. Tacrolimus Capsules (Received) 377. Tamsulosin Hydrochloride Capsules (Received) 380. Terazosin Capsules (Received) 383. Terbinane Tablets (Received) 386. Terconazole Vaginal Suppositories 389. Tetracycline Hydrochloride Periodontal Fiber 392. Tiopronin Tablets 395. Topiramate Tablets (Received) 398. Trandolapril and Verapamil Hydrochloride Extended-Release Tablets 401. Tranylcypromine Sulfate Tablets (Received) 404. Triamcinolone Acetonide Nasal Suspension 407. Trimipramine Maleate Capsules 410. Trolamine Salicylate Gel 413. Urea Cream 416. Venlafaxine Tablets (Received) 419. Voriconazole Injection 321. Promethazine Hydrochloride and Dextromethorphan Hydrobromide Syrup (Received) 324. Pseudoephedrine Hydrochloride and Naproxen Sodium Extended-Release Tablets 327. Pseudoephedrine Sulfate and Dexbrompheniramine Maleate Extended-Release Tablets 330. Pyrilamine Maleate Injection 333. Ramipril Capsules (Received) 336. Reserpine and Polythiazide Tablets 339. Risperidone Orally Disintegrating Tablets 342. Rocuronium Bromide Injection 345. Salicylic Acid and Sulfur Cleansing Lotion 348. Salicylic Acid Cream 351. Salmeterol Xinafoate Inhalation Powder 354. Sertraline Hydrochloride Oral Solution 357. Sodium Bicarbonate, Sodium Citrate, and Sodium Tartrate for Oral Suspension 360. Sodium Phenylbutyrate Tablets 363. Sodium Salicylate and Sulfur Shampoo 366. Sucralfate Oral Suspension 369. Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution 372. Sumatriptan Injection 375. Tacrolimus Injection 378. Technetium Tc 99m Teboroxime Injection 381. Terazosin Tablets (Received) 384. Terbinane Topical Solution 387. Testosterone Transdermal Gel 390. Theophylline Extended-Release Tablets 393. Tolnaftate Topical Aerosol Solution 396. Torsemide Injection 399. Trandolapril Tablets 402. Tretinoin Capsules 405. Triuridine Ophthalmic Solution 408. Triprolidine and Pseudoephedrine Hydrochlorides and Codeine Phosphate Syrup 411. Trolamine Salicylate Topical Emulsion 414. Vecuronium Bromide for Injection 417. Verapamil Hydrochloride Capsules 420. Voriconazole Oral Suspension
# 2008
1115
Small Molecules (Drug Products)As of June 20, 2008 (Continued) 421. Voriconazole Tablets 424. Yttrium Y-90 Microspheres Injection 427. Zinc Acetate Capsules 430. Zoledronic Acid for Injection 422. Yttrium Y-90 Chloride Solution 425. Zaleplon Capsules 428. Zinc Tridosium Pentetate Injection 431. Zonisamide Capsules (Received) 423. Yttrium Y-90 Glass Microspheres 426. Zidovudine and Lamivudine Tablets (Received) 429. Ziprasidone Hydrochloride Capsules
ExcipientsAs of June 20, 2008 1. Acetone Sodium Bisulte 4. Acrylic Acid-Octyl Acrylate Copolymer 7. Allantoin-Sodium Pyrrolidone Carboxylate 10. Aluminum Oxide 13. Aluminum Sodium Sulfate 16. Ammonium Calcium Alginate 19. Beeswax, Synthetic 22. Benzyl Nicotinate 25. Butadiene-Styrene Rubber 28. Butylphthalyl Butylglycolate 31. Calcium Alginate and Ammonium Alginate 34. Calcium Phosphate Monobasic 37. Calcium Sorbate 40. Calteridol Calcium 43. Carbon 46. Carboxymethylcellulose Potassium 49. Cholic Acid 52. Cocamide Oxide 55. Cutina 58. Decanoic Acid 61. Dextrin Palmitate 64. Diacetyl Phosphate 67. Diuoroethane 70. Diisopropyl Adipate 73. Dimethyl Dicarbonate 76. Dipropylene Glycol 79. Disodium Inosinate 82. Docusate Sodium/Sodium Benzoate 85. Ethoxyquin 88. Ethyl Maltol (Received) 91. Ferric Ammonium Citrate 94. Ferric Phosphate 97. Ferrous Glycinate 100. Formic Acid 103. Geraniol 106. Glycerol Ester of Gum Rosin (Ester Gum) 109. Glyceryl Ricinoleate 112. Glycofurol 115. Heptylparaben 118. Hexanetriol(-1,2,6-) 121. Hydroxylated Lecithin 124. Iron Subcarbonate 127. Isopropyl Isostearate
# 2008
2. Acetylated Monoglycerides 5. Albumin Colloidal 8. Aluminum Ammonium Sulfate 11. Aluminum Potassium Sulfate 14. Aluminum Stearate 17. Ammonium Phosphate 20. Benzododecinium Bromide 23. Beta Naphthol 26. Butylated Hydromethylphenol 29. Calcium Acid Pyrophosphate 32. Calcium Bromide 35. Calcium Propionate 38. Calcium Stearoyl Lactylate 41. Capric Acid 44. Carboxymethyl Starch 47. Cetostearyl Isononanoate 50. Cinnamaldehyde 53. Cocoyl Caprylocaprate 56. Cystine 59. Decyl Oleate 62. Dextrins Modied 65. Dichlorouoromethane 68. Diglycol Stearate 71. Diisopropylbenzothiazyl-2-Sulfenamide 74. Dimyristoyl Lecithin 77. Disodium Edisylate 80. Disodium Monooleamide Sulfasuccinate 83. Erythrosine 86. Ethyl Hexanediol 89. Ethylene Dichloride 92. Ferric Citrate 95. Ferric Pyrophosphate 98. Ferrous Lactate 101. Furcelleran 104. Glutamic Acid Hydrochloride 107. Glyceryl Laurate 110. Glyceryl Tristearate 113. Glycol Stearate 116. Hexadecyl Isostearate 119. Hydrocarbon Gel 122. Indigotine 125. Isobutylated-Isoprene Copolymer 128. Isopropyl Stearate
3. Aconitic Acid (Achilleic Acid) 6. Aliphatic Polyesters 9. Aluminum Lactate 12. Aluminum Silicate 15. Ammonium Bicarbonate 18. Batylalcohol Monostearate 21. Benzyl Chloride 24. Brominated Vegetable Oil 27. Butylene Glycol 30. Calcium Alginate 33. Calcium Chloride Solution 36. Calcium Pyrophosphate 39. Caldiamide Sodium 42. Caprylic/Capric Diglyceryl Succinate 45. Carboxymethylamylopectin Sodium 48. Chlorodiuoroethane 51. Cocamide Diethanolamine 54. Crystal Gum 57. Dammar Gum 60. Desoxycholic Acid 63. Diacetyl Tartaric Acid Esters of Monoand Diglycerides 66. Diethyl Sebacate 69. Diisobutyl Adipate 72. Dilauryl Thiodipropionate 75. Dimyristoyl Phosphatidylglycerol 78. Disodium Guanylate 81. D-Mannose 84. Ethoxylated Mono- and Diglycerides 87. Ethyl Linoleate 90. Ethylurea 93. Ferric Oxide, Brown 96. Ferrous Citrate 99. Fluorochlorohydrocarbons 102. Gentistic Acid 105. Gluten 108. Glyceryl Palmitate 111. Glycine Hydrochloride 114. Heptauoropropane 117. Hexane 120. Hydroxyethylmethylcellulose 123. Iron Carbonyl 126. Isooctylacrylate 129. Isostearic Acid
1116
ExcipientsAs of June 20, 2008 (Continued) 130. Isostearyl Alcohol 133. Lactylated Fatty Acid Esters of Glycerol and Propylene Glycol 136. Lanolin Alcohols, Acetylated 139. Lauramine Oxide 142. Lauric Diethanolamide 145. Lecithin, Hydroxylated 148. L-Leucine 151. Macrogolglycerol Triisostearate 154. Magnesium Aspartate 157. Magnesium Tartrate 160. Maltol Isobutyrate 163. Manganese Glycerophosphate 166. Medronate Disodium 169. Methylchloroisothiazolinone 172. Mineral Spirits 175. Monosodium Citrate 178. Myristyl Lactate 181. Naphtha 184. Nutmeg Oil 187. Palm Kernel Oil (Received) 190. Pentetate Pentasodium 193. Phenylmercuric Nitrate 196. Polyglycerol Esters of Fatty Acids 199. Polyoxyl Stearate (USP has 40) 202. Polysorbate 65 205. Polyvinylpyrrolidone Ethylcellulose 208. Potassium Carbonate Solution 211. Potassium Glycerophospate 214. Potassium Phosphate 217. Potassium Pyrophosphate 220. Potassium Sulte 223. Propylene Glycol Diacetate 226. Rosin 229. Sodium Aluminosilicate (Received) 232. Sodium Aspartate 235. Sodium Carbonate Hydrate 238. Sodium Chlorate 241. Sodium Dehydroacetate 244. Sodium Ferric Pyrophosphate 247. Sodium Laureth Sulfate 250. Sodium Magnesium Aluminosilicate 253. Sodium Metaphosphate, Insoluble 256. Sodium Polyphosphates Glassy 259. Sodium Pyrrolidone Carboxylate 262. Sodium Stearoyl Lactylate 265. Sodium Trioleate 268. Stannous Tartrate 271. Stearalkonium Chloride 131. Lactobionic Acid (Received) 134. Lactylic Esters of Fatty Acids 137. Lanolin Hydrous 140. Lauric Myristic Diethanolamide 143. Lavender Oil 146. L-Glutamic Acid (Received) 149. Macrogol Sorbitan Tristearate 152. Magnesium Aluminum Silicate Hydrate 155. Magnesium Phosphate Tribasic 158. Malt Syrup 161. Manganese Chloride 164. Manganese Hypophosphite 167. Medronic Acid 170. Methylisothiazolinone 173. Monoisostearyl Glyceryl Ester 176. Mullein Leaf 179. N,N-Bis(2-Hydroxyethyl)Stearamide 182. N-Methylpyrrolidone (Received) 185. Octanoic Acid 188. Pentasodium Triphosphate 191. Phenprobamate 194. Pine Oil 197. Polyglycerol Polyricinoleic Acid 200. Polypropylene Oleate 203. Polyvinylacetal Diethylanoacetate 206. Potassium Acid Tartrate 209. Potassium Dichloroisocyanurate 212. Potassium Iodate 215. Potassium Phosphate Tribasic 218. Potassium Stearate 221. Potassium Tripolyphosphate 224. Propylene Glycol Mono- and Diesters 227. Silicone 230. Sodium Aluminum Phosphate Acidic 233. Sodium 236. Sodium 239. Sodium 242. Sodium 245. Sodium Bisulfate Carboxymethyl Betaglucan Citrate, Dibasic Diacetate Ferrocyanide 132. Lactose Ferrin, Bovine 135. Lanolin (Wool Fat), Hydrogenated 138. L-Ascorbyl Stearate 141. Lauric Acid 144. L-Cysteine Monohydrochloride 147. Linoleic Acid (Received) 150. Macrogolglycerol Cocoates 153. Magnesium Aspartame Dihydrate 156. Magnesium Phosphate, Diabasic, Trihydrate 159. Maltitol Syrup 162. Manganese Citrate 165. Medical Antifoam Emulsion C 168. Methyl Chloride 171. Microcrystalline Cellulose, Silicied (Received) 174. Monopotassium Glutamate Monohydrate 177. Myristyl Gamma-Picolinium Chloride 180. N-Acetyl-L-Methionine 183. Non-Pareil Seeds 186. Oxystearin 189. Pentetate Calcium Trisodium 192. Phenylmercuric Acetate 195. Polacrilin 198. Polyoxyethylene Castor Oil (USP has 35) 201. Polypropylene Stearyl Ether 204. Polyvinylpolypyrrolidone 207. Potassium Bromate 210. Potassium Gibberellate 213. Potassium Nitrite 216. Potassium Polymetaphosphate 219. Potassium Sulfate 222. Propyl Propionate 225. Rice Bran Wax 228. Sodium Acid Pyrophosphate 231. Sodium Aluminum Phosphate Basic 234. Sodium Bisulte 237. Sodium Caseinate 240. Sodium Citrate, Monobasic 243. Sodium Erythorbate 246. Sodium Hypophosphite (Received) 249. Sodium Lauryl Sulfoacetate 252. Sodium Malate 255. Sodium Methylate 258. Sodium Pyrophosphate 261. Sodium Sesquinoleate 264. Sodium Trimetaphosphate 267. Soy Polysaccharides 270. Starch, Pregelatinized Tapioca 273. Stearyl Monoglyceridyl Citrate
248. Sodium Lauroyl Sarcosinate 251. Sodium Magnesium Silicate 254. Sodium Metasilicate 257. Sodium Potassium Tripolyphosphate 260. Sodium Sesquicarbonate 263. Sodium Thiomalate 266. Sodium Tripolyphosphate 269. Starch, Pregelatinized Corn 272. Stearyl Citrate
# 2008
1117
ExcipientsAs of June 20, 2008 (Continued) 274. Succinylated Monoglycerides 277. Sucrose Stearate (Received) 280. Tallow 283. Tetrauoroethane 286. Tribehenin 289. Trimyristin 292. Vegetable Oil 295. Wheat Gluten (Received) 275. Sucrose Acetate Isobutyrate 278. Sugar Fruit Fine 281. Tallow Glycerides 284. Thioglycerol 287. Triceteareth-4 Phosphate 290. Trisodium Citrate 293. Wheat Flour 296. Whey 276. Sucrose Fatty Acid Esters 279. Sulfobutyl Ether Beta Cyclodextrin (Received) 282. Tallow Oil 285. Thyme Oil 288. Trichloroethylene 291. Trolamine Lauryl Sulfate 294. Wheat Germ Oil
# 2008
STIMULI TO THE REVISION PROCESS
Stimuli articles do not necessarily reect the policies of the USPC or the USP Council of Experts
1343
INSTRUCTIONS TO AUTHORS
Contributions in the form of original research reports, evaluations of new and existing compendial methods, and other commentaries and articles relevant to drug standards or to USPNF revision will be considered for publication in Pharmacopeial Forum under the section Stimuli to the Revision Process. Manuscripts are received with the explicit understanding that they have not been published previously in any language or medium and that they are not simultaneously under consideration by any other publication. All manuscripts are subject to review by USP headquarters staff, Committee members, or qualied outside referees, and if accepted for publication they will be subject to editing by USP staff. Accepted manuscripts become the property of the USP Convention (USPC) and may not be subsequently published elsewhere without written permission from the USPC. Authors are also responsible for obtaining permission for reprinting any illustrations that have been published elsewhere. AbstractInclude an abstract of not more than 250 words stating the purpose and the results or conclusions of the article. Style and UsageStimuli articles generally follow the current Chicago Manual of Style except in scientic usage (numbers, abbreviations, etc.). For the latter, authors should use the current AMA Manual of Style or the current ACS Style Guide. Authors may usefully consult a current copy of Pharmacopeial Forum. ReferencesConsult the current AMA Manual of Style, which is generally consistent with the National Library of Medicines Recommended Formats for Bibliographic Citation. A current copy of Pharmacopeial Forum will offer examples of reference formats. CopyrightCopyright transfer documents will be sent to authors after manuscripts have been accepted for publication. Contact PersonUSP will designate a Scientic Liaison in the Documentary Standards Division as the corresponding author. This ensures that USP receives all comments generated by the Stimuli article. Authors should contact the Scientic Liaison if they would like to receive copies of comments generated by their Stimuli articles. Submission InstructionsManuscripts must be submitted both as an electronic le and as a printed copy of the electronic le. Submit the text in Microsoft1 Word or another current word-processing application. The preferred format for graphics submitted electronically is tagged image le format (TIFF). Photocopies are not acceptable. Manuscripts submitted for publication should be addressed to: Pharmacopeial Forum Executive Secretariat, USP 12601 Twinbrook Pkwy. Rockville, MD 20852
Stimuli to the Revision Process
# 2008
The United States Pharmacopeial Convention, Inc. All Rights Reserved.
1345
General Chapter on Inorganic Impurities: Heavy Metals

USP Ad Hoc Advisory Panel on Inorganic Impurities and Heavy Metals and USP Staff*
ABSTRACT In the ICH Q3A Impurities in Drug Substances guidance, impurities are classied as organic, inorganic, and residual solvents. Within the inorganic impurities classication, the metals listed in Table 1 are important to control in food, dietary supplements, and drug articles. Many toxic metal impurities found in pharmaceutical articles have been controlled for years by application of the Heavy Metals test described in USPNF General Chapter Heavy Metals h231i. However, the procedures and the methods contained in h231i lack the sensitivity, specicity, and recovery to monitor properly the levels of these metals. A number of additional chapters for the control of specic metals and other inorganic impurities are contained in USPNF. This Stimuli article proposes a new USP General Chapter for the control of inorganic impurities in drug and dietary supplement articles intended for use in humans. For the purposes of this article, inorganic impurity, metal, and element all refer to those elements listed in Table 1. The proposed new General Chapter recommends procedures that rely on modern analytical technology and includes limits that are based on toxicity and exposure levels for the selected metals. The new General Chapter also introduces a performance-based approach for the selection of the appropriate technology. This chapter is proposed to replace h231i and may impact other General Chapters that control metals. INTRODUCTION Among the category of inorganic impurities, metal impurities have long been monitored in food and drug articles intended for consumption by humans and other animals. For purposes of this General Chapter, drug articles include: drug substances and products (including natural-source and rDNA biologics) and excipients. Dietary supplements and their ingredients are also included, but other foods and food ingredients will not be addressed. Some metals may pose no signicant health hazard at sufciently low exposure levels, when present as certain complexes, at certain oxidation states, or in organic combinations. This chapter should be considered a screening method to identify the presence of potentially hazardous elements. Where speciation of an element is important, further testing is necessary. In these cases, the monograph will include specic instructions for appropriate identication and control. The topic of speciation will not be covered further in this article. Some inorganic impurities are toxic at low levels, and these impurities should be monitored to ensure safety. Sources of inorganic impurities include those that are deliberately added to the process (e.g., catalysts), those that are carried through a process that is conducted according to good manufacturing practices (e.g., undetected contaminants from starting materials or reagents), those coming from the process (e.g., leaching from pipes and other equipment), and those that occur naturally (e.g., from naturally derived plant or mineral sources). Regardless of source, the control of these impurities may be certied by a vendor, but purchasers also must corroborate the absence of impurities before using these materials in a manufactured article. The General Chapters Expert Committee of the USP Council of Experts formed an Ad Hoc Advisory Panel on Inorganic Impurities and Heavy Metals to assist the Expert Committee in revision of General Chapter Heavy Metals h231i. As drafted by this Ad Hoc Advisory Panel and revised by the Expert Committee, the proposed revision species that the level of
* Correspondence should be sent to: Kahkashan Zaidi, PhD, Senior Scientist, Documentary Standards Division, US Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790; tel. 301.816.8269; e-mail kxz@usp.org.
each inorganic impurity should not exceed the limit dened in Table 1 or otherwise specied in the individual monograph. This level is determined by concomitant comparison with a monitor solution and USP Reference Standard solution(s). The selection of an instrumental technique and a procedure for the evaluation of the inorganic impurities specied in Table 1 requires the evaluation of a large number of variables including, among others, sensitivity, precision, accuracy, compatibility, time, and cost. The method selected may include plasma spectrochemistry, atomic absorption spectroscopy, or any other method that displays requisite accuracy (trueness and uncertainty) and established sensitivity and specicity. Meeting this requirement must be demonstrated experimentally using the USP Reference Standard(s). Any procedure that provides measurement values within 20% of the certied concentration for each element in the appropriate USP Reference Standard(s) is considered to be an acceptable procedure to demonstrate compliance. A guide for the selection of a procedure is presented in Figure 1. When a manufacturer does not have a preferred procedure, or when the preferred procedure does not meet criteria for performance described above, proceed as directed in the remainder of this General Chapter. ProcedureDetermine the levels of individual inorganic impurities by the test, unless the individual monograph species otherwise. ReagentsAll reagents used for the preparation of sample and standard solutions should be free of inorganic impurities in accordance with Plasma Spectrochemistry h730i. Commercial, National Institute of Standards and Technologytraceable elemental stock standards, either single element or multi-element, containing Al, Sb, As, Be, B, Cd, Cr, Co, Cu, In, Ir, Fe, Pb, Li, Mg, Mn, Hg, Mo, Ni, Os, Pd, Pt, Rh, Rb, Ru, Se, Sr, Tl, Sn, W, or Zn at a recommended concentration of 100 mg/mL or greater also are used as reagents.
# 2008
1349
The Cadaver Skin Absorption Model and the Drug Development Process*
Thomas J. Franz, MS, MD, Paul A. Lehman, MS, Sam G. Raney, PhD, PRACS Institute, Ltd.Cetero Research
ABSTRACT Drug absorption through the skin can be assessed simply by the use of in vitro mounted human cadaver skin, and the method has been extensively utilized by industry in the development of topical and transdermal drugs. Although the Food and Drug Administration has not formally accepted this approach, examination of various applications of the technique during the past 40 years demonstrates its value as a valid surrogate for in vivo measurements of bioavailability and bioequivalence. Newer data, in particular, reveal the sensitivity of the model and recommend its wider use in all phases of the drug development process. INTRODUCTION A crucial element in the development of topical and transdermal drug products is evaluation of the percutaneous absorption of the active pharmaceutical ingredient (API). Generally, the goal for topical products is to maximize cutaneous delivery of the API, whereas for transdermal products the goal is to achieve a specic rate of absorption sufcient to achieve a systemic blood level within the therapeutic range for its intended indication. In either situation success depends on identifying the optimum formulation from a large number of prototypesan onerous task for most therapeutic classes if screening must be conducted in human subjects. Only the topical glucocorticoid products are unique because a pharmacodynamic endpoint (vasoconstriction) exists by which their percutaneous absorption can be relatively easily assessed in human subjects (1, 2). To circumvent the need for time-consuming and expensive human pharmacokinetic studies as a screening mechanism for formulation optimization and to allow formulation development to proceed during the preclinical phase of drug development (without the need for animal safety data and submission of an investigational new drug application), pharmaceutical scientists have made extensive use of a simple in vitro model that relies on excised human skin mounted in diffusion chambers (36). The basis of the model is the fact that the barrier properties of skin are preserved after death, and, as a result, the rate of drug absorption measured in vitro accurately mimics the in vivo state. Although much of these data reside only in corporate archives, sufcient data can be found in the literature published during the past four decades to clearly illustrate the utility, versatility, and power of the model. What is puzzling, however, is that the Food and Drug Administration (FDA) has not made greater use of data generated by this highly relevant model in their evaluation of new drug applications (NDAs) and abbreviated new drug applications (ANDAs). In the past although some reviewers have requested cadaver skin data in order to address specic review issues, others have claimed the model is not generally accepted and have suggested that data derived from the model, although supplemental, serve no pivotal purpose in the review process. The latter argument seems incongruous given the vital role the cadaver skin model plays within sponsor companies in the development of the products under review. Tacit acceptance of the method by industry based on successful transfer of products from labora* Correspondence should be addressed to: Vinod P. Shah, PhD, Consultant, Documentary Standards Division, US Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790; tel. 301.816.8208; e-mail vps@usp.org.
tory to market argues strongly for the validity of the model. The purpose of this Stimuli article is to examine the utility of the cadaver skin model at various points within the drug development process. PRECLINICAL PHASETOPICAL DRUG PRODUCTS Formulation Development The rst important class of topical therapeutic agents that had a major impact on dermatologic practice was the glucocorticoids, many of which were introduced in the 1950s and 1960s (7, 8). At this time use of in vitromounted human skin to study percutaneous absorption was just evolving, and the model had not been applied to drug development. Similarly the importance of the vehicle in drug delivery was not well understood, and products that contained various strengths of the same API (e.g., 0.025%, 0.1%, or 0.5% triamcinolone acetonide, and 1.0% or 2.5% hydrocortisone) were marketed with the mistaken belief that increased concentration would lead to increased efcacy. Years later, after the human vasoconstrictor (VC) assay was developed, the different product strengths for both triamcinolone acetonide and hydrocortisone were shown to be of equal potency (9). Rational vehicle design came a decade later and is illustrated by the work done at Syntex Laboratories during the development of the rst high-potency glucocorticoid, uocinonide (10). The work established not only the importance of drug concentration in the vehicle, specically soluble drug concentration, but also the ability of the drug to leave the vehicle and enter the stratum corneum (partitioning). Of particular interest is the fact that an integral part of the drug development scheme was the use of the cadaver skin model as a means to validate the theoretical considerations and chemistry involved in the formulation process. For the rst time formulation scientists demonstrated the pivotal role of the cadaver skin model as an intermediate step between chemistry and clinic. Subsequently, this format has become the blueprint for the development of other glucocorticoid preparations as well as topical formulations, in general (11, 12).
# 2008

Forum 34

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Forum 34

Uploaded by

Copyright:

Available Formats

Table of Contents*

PHARMACOPEIAL FORUM VOL. 34 NO. 5 SEPT.OCT. 2008

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

1344 1345 1349 1357 1359

The United States Pharmacopeial Convention

All Rights Reserved.

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

E-MAIL dra@usp.org cma@usp.org

PHONE (301) 816-8184 (301) 816-8139

fa@usp.org scb@usp.org dkb@usp.org kxb@usp.org web@usp.org

dac@usp.org lnc@usp.org tlc@usp.org ddc@usp.org

(301) 816-8307 (301) 816-8385 (301) 816-8234 (301) 816-8215

Monograph Development Antivirals and Antimicrobials (MD-AA)

(301) 998-6303 (301) 816-8178 Veterinary Drugs (VET)

(301) 816-8389 (301) 816-8343

Dietary SupplementsNonBotanicals (DSN)

USP Spanish Edition; General Chapters (GC)

The United States Pharmacopeial Convention

All Rights Reserved.

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

STAFF DIRECTORY (continued)

STAFF Desmond G. Hunt, Ph.D., Scientist

PHONE (301) 816-8341

pj@usp.org rhl@usp.org agl@usp.org

(301) 998-6827 (301) 816-8335 (301) 816-8382

(301) 816-8336 (301) 816-8320

mxm@usp.org jm@usp.org ktm@usp.org tsm@usp.org

(301) 998-6786 (301) 816-8243

Veterinary Medicine Information (VMI) Sterile Compounding (SCC)

General Chapters (GC); Statistics (STAT) Drug Information

dsp@usp.org dgp@usp.org mxp@usp.org sxr@usp.org hr@usp.org rr@usp.org

Monograph Development Cardiovascular (MD-CV)

The United States Pharmacopeial Convention

All Rights Reserved.

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

STAFF DIRECTORY (continued)

PHONE (301) 816-8379

lxs@usp.org dns@usp.org rxs@usp.org sps@usp.org mhs@usp.org cxs@usp.org

Dietary Supplements Botanicals (DSB) Food Additives (FA)

tzs@usp.org nrs@usp.org aey@usp.org rst@usp.org

yt@usp.org dwv@usp.org hw@usp.org

(301) 816-8321 (301) 998-6828 (301) 816-8351

aw@usp.org aww@usp.org kxz@usp.org

(301) 816-8305 (301) 816-8607 (301) 816-8269

The United States Pharmacopeial Convention

All Rights Reserved.

POLICIES AND ANNOUNCEMENTS

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

Policies and Announcements

The United States Pharmacopeial Convention

All Rights Reserved.

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

POLICIES AND ANNOUNCEMENTS

Pharmacopeial Forum PF 34(2) PF 34(3) PF 34(4) PF 34(5) PF 34(6) PF 35(1)

Publication Date February 2009 June 2009 November 2009

Ofcial Date August 2009 December 2009 May 2010

The United States Pharmacopeial Convention

All Rights Reserved.

POLICIES AND ANNOUNCEMENTS

Pharmacopeial Forum Vol. 34(5) [Sept.Oct. 2008]

Policies and Announcements

The United States Pharmacopeial Convention

All Rights Reserved.