Study on accelerated evaluation system for release profiles of covered-rod type silicone formulation using indomethacin as a model drug

• Published in: Journal of controlled release Vol. 94; no. 2; pp. 337 - 349
• Main Authors: Maeda, Hiroo, Sugie, Toshihiko, Sano, Akihiko, Kawasaki, Hiromu, Kurosaki, Yuji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.02.2004; Elsevier
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; Covered-rod; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Drug Evaluation, Preclinical - methods; General pharmacology; In vitro release test; Indomethacin; Indomethacin - chemistry; Indomethacin - pharmacokinetics; Medical sciences; Models, Chemical; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Release profile; Silicone; Silicones - chemistry; Silicones - pharmacokinetics; Solubility - drug effects; In vitro release test; Covered-rod; Indomethacin; Silicone; Release profile; Drug; Prostaglandin-endoperoxide synthase; Evaluation; Pharmaceutical technology; Enzyme; Rod; Indometacin; Enzyme inhibitor; Tocolytic; Non steroidal antiinflammatory agent; Formulation; Indoleacetic acid derivatives; Oxidoreductases; Siloxane polymer; Release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2003.10.013

The purpose of this study was to establish a method allowing rapid evaluation in vitro of the profiles of drug release from covered-rod type silicone formulation (CR silicone formulation), which releases drug for a prolonged period of time. Three CR silicone formulations containing indomethacin (IDM) with different release profiles were used in this study. The release of IDM was accelerated in a mixture of methanol and water (MeOH/water) compared with in phosphate-buffered saline (PBS) added by Tween 20 (PBS-based solvent). The velocity of IDM release varied depending on the composition of the MeOH/water. The change in release velocity was dependent on the solubility of IDM and the permeability of IDM through the silicone membrane. In all the tested formulations, the release rates of IDM estimated in 90% (v/v) MeOH/water were equally 14.6 times faster than those estimated in PBS-based solvent. Release of IDM from the cross-sections and lateral side evaluated by a bi-directional elution cell were accelerated in the MeOH/water in a similar degree. By introducing a common factor to shorten the time axis in all formulations, a fairly good agreement was observed between the two release profiles obtained in the accelerated MeOH/water system and the usual PBS-based solvent system. These results indicate that MeOH/water system enables to reduce the period for evaluation of profiles of drug release from CR silicone formulations in reflecting their release characteristics in usual PBS-based solvent system.