Professional Documents
Culture Documents
0.930 0.029
0.840 0.045
0.880 0.062
0.920 0.061
0.936 0.073
0.996 0.010
0.830 0.069
0.853 0.036
0.920 0.052
1.000 0.000
1.000 0.000
3.0 1.7
3.0 0.0
2.0 1.7
1.7 1.9
3.7 1.9
2.3 1.0
5.3 2.6
2.7 1.0
5.3 2.6
1.0 0.0
1.0 0.0
0.770 0.045
0.800 0.076
0.820 0.107
0.833 0.038
0.793 0.066
0.900 0.062
0.806 0.095
0.830 0.035
0.873 0.066
0.990 0.017
0.980 0.173
4.0 2.9
13.0 4.5
3.3 2.6
15.3 2.6
16.0 4.5
15.0 4.5
5.7 2.6
14.0 1.7
12.0 4.5
2.3 2.9
3.0 1.7
+
+
+
+
+
+
-
Evaluations were performed for three samples of each formulation; b F factor (mean S.D.); the ratio
between the height of sediment at time of evaluation and the height of the suspension at time zero ; c Res.
(resuspendability, mean S.D.); the number of times of shaking under 180o for homogeniziatior of the
suspensions, d Cake: cake formation
100.9 2.2
98.7 2.9
99.3 1.2
102.3 3.1
101.1 2.8
98.2 1.6
101.2 3.1
101.7 2.8
99.9 3.3
102.7 2.9
101.4 3.1
Day 45
161.9
153.1
150.1
145.0
140.8
134.1
158.2
153.9
156.3
125.9
128.1
2.8
3.1
2.4
2.2
3.8
2.8
6.7
2.8
4.2
3.1
3.5
Day 150
188.1
176.2
174.1
169.7
163.7
151.2
183.2
181.7
132.9
143.1
146.2
7.6
5.0
6.6
3.6
4.1
2.6
7.9
5.4
2.8
3.1
4.1
MS 6
MS 7
MS10
Figure 4. Acetaminophen particle size in some suspensions after freeze-thaw cycling procedure; MS
1: without PVP and BSA; MS 6: containing 100 mg of PVP; MS 7: containing 50 mg of BSA; MS 10:
containing PVP (50 mg) and BSA (80 mg)
process can start immediately and the drug
molecules resulting from dissolution of the
crystal can diffuse through the adsorbate into the
bulk liquid phase (18).
The freeze-thaw cycling technique is
particularly applicable to stress suspensions for
testing the stability. This treatment promotes
particle growth and may be useful in prediction
of the state of suspensions after long storage at
room temperature. Thus it is of prime importance to be alert for changes in absolute particle
size, particle size distribution, and crystal habit
1.
2.
3.
4.
5.
6.
REFERENCES
Martin, A., Bustamante, P., Chun, A.H.C. (eds) (1993) Physical pharmacy, 4th. edn, Lea and
Febiger, Philadelphia, pp: 426, 431, 477.
Billany, M.R. (1988) Suspensions. In: Aulton, M.E. (ed) Pharmaceutics: the science of dosage
form design, Churchill Livingstone, London, p: 270.
Zatz, J.L. (1985) Physical stability of suspensions. J. Soc. Cosmet. Chem. 36: 393-411.
Esumi, k., Wake, T., Terayama, H. (1998) Preparation of stable aqueous dispersion of drug in the
presence of polymer as stabilizer. Colloids Surf. B. 11: 223-229.
Sha, Z. and Palosaari, S. (2000) Mixing and crystallization in suspensions. Chem. Eng. Sci. 55:
1797-1806.
Duro, R., Vasquez, M.J., Gomez-A, J.L., Concheiro, A., Sauto, C. (1993) Stabilization of
mebendazole suspension with cellulose ethers. Pharmazie, 48: 602-605.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Ntawukulilyayo, J.D., De Smart, S.C., Demeester, J., Remon, J.P. (1996) Stabilization of
suspensions using sucrose esters and low substituted n-octenylsuccinate starch-xanthan gum
associations. Int. J. Pharm. 128: 73-79.
Duro, R., Alvarez, C., Martinez-Pacheco, R., Gomez-Amoza, J.L., Concheiro, A., Sauto, C.
(1998) The adsorption of cellulose ethers in aqueous suspensions of pyrantel pamoate: effects on
zeta potential and stability. Eur. J. Pharm. Biopharm. 45: 181-188.
Zatz, J.L., Sarpotdar, P., Gergich, G., Wong, A. (1981) Effect of surfactants on the flocculation
of magnesium carbonate suspensions by xanthan gum. Int. J. Pharm . 9: 315-319.
Kawashima, Y., Iwamoto, T., Niwa, T., Takeuchi, H., Itoh, Y. (1991) Preparation and
characterization of a new controlled release ibuprofen suspension for improving suspendability.
Int. J. Pharm. 75: 25-36.
Terayama, H., Okumura, K., Sakai, K., Torigoe,K., Esumi, K. (2001) Aqu eous dispersion
behavior of drug particles by addition of surfactant and polymer. Colloids Surf. B. 20: 73-77.
Pearson, J.T. and Varney, G. (1969) Crystal growth studies involving phase transitions in
aqueous drug suspensions. J. Pharm. Pharmacol. 21: 25-36.
Idkaidek, N.M., Najib, N.M. (2000) Enhancement of oral absorption of metronidazole
suspension in humans. Eur. J. Pharm. Biopharm. 50: 213-216.
Deicke, A. and Sverkrp, R. (2000) Dose uniformity and redispersibility of pharmaceutical
suspensions 2: assessment of three commercial erythromycin ethyl succinate oral liquids. Eur. J.
Pharm. Biopharm. 49: 73-78.
Luthala, S. (1992) Effect of sodium lauryl sulfate and polysorbate 80 on crystal growth and
aqueous solubility of carbamazepine. Acta. Pharm. Nordica. 4(2): 85-90.
Bonhomme-Faivre, L., Mathieu, M.C., Dipraetere, P., Grossiord, J.L., Seiller, M. (1997)
Formulation of charcoal suspension for intratumoral injection: influence of the pluoronic F68
concentration. Int. J. Pharm. 152: 251-255.
Motawi, A.M., Mortadu, S.A.M., El-Khawas, F., El-Khodery, K.A. (1982) Crystal growth
studies of sulfathiazole aqueous suspension. Acta. Pharm. Technol. 28(3): 211-215.
Ziller K.H. and Rupprecht, H. (1988) Control of crystal growth in drug suspensions. Part
1:Design of a control unit and application to acetaminophen suspensions. Drug Dev. Ind. Pharm.
14: 2341-2370.
Luthala, S., Kahela, P., Kristoffersson, E. (1990) Effect of benzalkonium chloride on crystal
growth and aqueous solubility of carbamazepine. Acta. Pharm. Fenn. 99(2): 59-67.
Esumi, K., Itaka, M., Torigoe, K. (1999) Kinetics of simultaneous adsorption of Poly
(vinylpyrrolidone) and Sodium Dodecyl Sulfate on alumina particles. J. Coll. Interface Sci.
232(1): 71-75.
Patell, N.K., Kennon, L., Levinson, R.S. (1986) Pharmaceutical suspensions. In: Lachman, L.,
Lieberman, H.A., Kanig, J.L. (eds) The theory and practice of industrial pharmacy, Lea and
Febiger, Philadelphia, pp: 492-494.
Cumulative % of distribution
Cumulative % of distribution
without PVP
120
100
80
60
40
20
0
0
25
50
75
PVP 10 mg
120
100
80
60
40
20
0
25
50
75
MS1-0 day
MS1-45 day
MS2-0 day
MS2-150 day
PVP 30 mg
Cumulative % of distribution
Cumulative % of distribution
MS1-150 day
120
100
80
60
40
20
25
50
75
100
80
60
40
20
0
0
25
50
Cumulative % of distribution
Cumulative % of distribution
100
80
60
40
20
0
25
50
75
125
150
175
200
225
250
MS4-45 day
MS4-150 day
PVP 60 mg
100
MS4-0 day
MS3-45 day
MS3-150 day
120
75
MS2-45 day
PVP 50 mg
120
0
0
MS5-45 day
PVP 100 mg
120
100
80
60
40
20
0
0
25
50
MS6-45 day
MS6-150 day
275
Cumulative % of distribution
Cumulative % of distribution
BSA 50 mg
120
100
80
60
40
20
0
0
25
50
BSA 100 mg
120
100
80
60
40
20
0
0
25
50
75
MS8-0 day
MS7-45 day
MS8-45 day
MS8-150 day
MS7-150 day
Cumulative % of distribution
25
50
75
MS9-45 day
MS9-150 day
120
Cumulative % of distribution
Cumulative % of distribution
100
80
60
40
20
0
25
50
75
25
50
75
MS11-45 day
MS10-0 day
MS10-45 day
MS10-150 day