The document discusses several key factors that influence drug absorption from the gastrointestinal tract, including drug properties like pKa and lipophilicity, dosage form characteristics such as disintegration time, and patient-related factors like gastric emptying time and gastrointestinal pH. The pH partition hypothesis is described, which proposes that the fraction of unionized drug, its lipophilicity, and gastrointestinal pH govern absorption. Drug classes are provided based on pKa to illustrate how this property influences where in the GI tract absorption occurs.
The document discusses several key factors that influence drug absorption from the gastrointestinal tract, including drug properties like pKa and lipophilicity, dosage form characteristics such as disintegration time, and patient-related factors like gastric emptying time and gastrointestinal pH. The pH partition hypothesis is described, which proposes that the fraction of unionized drug, its lipophilicity, and gastrointestinal pH govern absorption. Drug classes are provided based on pKa to illustrate how this property influences where in the GI tract absorption occurs.
Copyright:
Attribution Non-Commercial (BY-NC)
Available Formats
Download as PPT, PDF, TXT or read online from Scribd
The document discusses several key factors that influence drug absorption from the gastrointestinal tract, including drug properties like pKa and lipophilicity, dosage form characteristics such as disintegration time, and patient-related factors like gastric emptying time and gastrointestinal pH. The pH partition hypothesis is described, which proposes that the fraction of unionized drug, its lipophilicity, and gastrointestinal pH govern absorption. Drug classes are provided based on pKa to illustrate how this property influences where in the GI tract absorption occurs.
Copyright:
Attribution Non-Commercial (BY-NC)
Available Formats
Download as PPT, PDF, TXT or read online from Scribd
• Polymorphism and amorphism • Pseudopolymorphism (hydrates/solvates) • Salt form of the drug • Lipophilicity of the drug • Drug pKa and pH • Drug stability Drug pKa and Lipophilicity and GI pH—pH Partition Hypothesis The pH partition theory (for molecular weight greater than 100) explain the process of absorption of drug is governed by: • The dissociation constant (pKa) of the drug. • The lipid solubility of the unionized drug (a function of drug Ko/w) • The pH at the absorption site. drugs are weak electrolytes hypothesis was based on the assumption that: • The GIT is a simple lipoidal barrier to the transport of drug. • Larger the fraction of unionized drug, faster the absorption. • Greater the lipophilicity (Ko/w) of the unionized drug, better the absorption. Drug pKa and Gastrointestinal pH lower the pKa of an acidic drug, stronger the acid higher the pKa of a basic drug, the stronger the base Henderson-Hasselbach equations for weak acids. ionized drug concentration PH = pKa+ log --------------------------- unionized drug concentration 10 pH - pKa % Drug Ionized = ----------------- x 100 1 + 10pH – pKa for weak bases, unionized drug concentration pH = pKa + log ----------------------------------- ionized drug concentration
10pKa - pH % Drug Ionized = -------------- x 100 1 +10pKa-pH Influence of drug pKa and GI pH on Drug Absorption Drugs pKa pH/site of absorption Very weak acids (pKa > 8.0) Pentobarbital 8.1 Unionized at all pH values Hexobarbital 8.2 absorbed along the entire length of GIT Phenytoin 8.3 Ethosuximide 9.3
Moderately weak acid (pKa 2.5 to 7.5)
Cloxacillin 2.7 Unionized in gastric pH and Aspirin 3.5 ionized in intestinal pH; better Ibuprofen 4.4 absorbed from stomach Phenylbutazone 4.5
Stronger acids (pKa < 2.5)
Disodium cromoglycate 2.0 Ionized at all pH values; poorly Absorbed from GIT Very weak bases (pKa < 5.0) Theophylline 0.7 Unionized at all pH values Caffeine 0.8 absorbed along the entire length of GIT Oxazepam 1.7 Diazepam 3.7
Moderately weak bases (pKa 5 to 11.0)
Reserpine 6.6 Ionized at gastric pH, Heroin 7.8 relatively unionized at intestinal pH; Codeine 8.2 better absorbed from intestine. Arnitriptyline 9.4
Stronger bases (pKa > 11.0)
Mecamylamine 11.2 Ionized at all pH values; Guanethidine 11.7 poorly absorbed from GIT. II. Dosage Form Characteristics and Pharmaceutic Ingredients Disintegration time (tablets/capsules) Dissolution time Manufacturing variables Pharmaceutic ingredients (excipients/adjuvants) Nature and type of dosage form Product age and storage conditions II. Dosage Form Characteristics and Pharmaceutic Ingredients Disintegration time (DT)(tablets/capsules) DT Dissolution Absorption Bioavailability sugar coated tablet have long DT DT of tablet dependent on binder/Compression Force (Hardness) Disintegration is increase by using disintegrants agent Manufacturing variables Method of granulation Wet granulation Dissolution more as compare to Dry granulation Compression Influence porosity, density, hardness, DT and dissolution Higher compression Pharmaceutic ingredients (excipients/adjuvants) Vehicle – Aqueous Non aqueous water misible Non aqueous water immiscible III.PATIENT RELATED FACTORS Include factors relating to the anatomical physiological and pathological characteristics of the patient Age Gastric emptying time intestinal transit time Gastrointestinal pH Disease states Blood flow through the GIT Gastrointestinal contents