Parenteral oil-based drospirenone microcrystal suspensions—Evaluation of physicochemical stability and influence of stabilising agents

详细信息    查看全文

• 作者：Stefanie Nippe ; ^a ; ^{stefanie.nippe@googlemail.com"" rel=""nofollow} ; Sascha General^a
• 关键词：Drospirenone ; Parenteral ; Oil ; Suspension ; Stability ; Injectability
• 刊名：International Journal of Pharmaceutics
• 出版年：2011
• 出版时间：15 September 2011
• 年：2011
• 卷：416
• 期：1
• 页码：181-188
• 全文大小：737 K

文摘

Drospirenone (DRSP) is a contraceptive drug substance with challenging physicochemical properties, due to insufficient solubility in aqueous and oil-based vehicles as well as low chemical stability in aqueous fluids. Although it is one of the most popular orally used progestins, no parenteral long-acting contraceptive containing the drug substance is marketed. An oil-based DRSP microcrystal suspension (MCS) might be an attractive formulation option. The main focus of this study was to investigate the physicochemical stability of such preparations. Moreover, syringeability and injectability via autoinjector were analysed using a materials testing machine. A high chemical stability of DRSP was found in oil-based vehicles. Span^® 83, cholesteryl oleate, lecithin, methyl cholate, Aerosil^® R972 and 200 Pharma were tested for increasing the physical stability of DRSP dispersions. Changes in viscosity, rheological properties, and solubility were analysed. The intention was to show a stabilising effect of the excipients without increasing viscosity and solubility. To evaluate the physical stability of DRSP MCS with and without addition of stabilising agents, sedimentation and particle growth after storage were examined. Especially, the silica derivatives Aerosil^® 200 and R972 Pharma influenced the physical stability positively.