Evaluation of the test system used for in vitro release of drugs for topical dermatological drug products.
The purpose of this research was to evaluate different parameters that can influence in vitro drug release from topical dermatological drug products such as creams, gels, and ointments. In vitro release from topical dermatological drug products was carried out by using a static diffusion cell, a synthetic membrane, and an appropriate receptor medium. The receptor medium was mixed by means of a magnetic bar rotated at 400 rpm. Experiments were designed to evaluate the influence of (i) receptor media, (ii) different lots of synthetic membranes, and (iii) agitation on drug release. Release experiments were also carried out to study inter- and intralot variability. The in vitro release test was used to evaluate the marketed glucocorticoid products. Among the parameters studied, the receptor medium was found to be the most important and critical variable that influenced drug release. The release rate ranged between 0.61 and 2.68 micrograms/cm2/min0.5 for betamethasone dipropionate, depending on the percentage of ethanol in the receptor medium. The drug release was not influenced by agitation or by different lots of synthetic membranes. Very small inter- and intralot variability was observed. These experiments establish the ruggedness of the in vitro diffusion cell test system used for the drug release measurements.
Shah
V P
VP
Office of Pharmaceutical Science, Food and Drug Administration, Rockville, Maryland 20852, USA. SHAHVI@cder.fda.gov
Elkins
J S
JS
Williams
R L
RL
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000737:chemistry; D000893:Anti-Inflammatory Agents; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation*; D002851:Chromatography, High Pressure Liquid; D003879:Dermatologic Agents; D004058:Diffusion; D005069:Evaluation Studies as Topic; D005079:Excipients; D005938:Glucocorticoids; D007202:Indicators and Reagents; D009824:Ointments; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000032:analysis*; D014481:United States; D014486:United States Food and Drug Administration
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D005079:Excipients; D005938:Glucocorticoids; D007202:Indicators and Reagents; D009824:Ointments; D004364:Pharmaceutical Preparations; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone