Selection and use of crystallization inhibitors for matrix-type transdermal drug-delivery systems containing sex steroids

• Published in: Journal of pharmacy and pharmacology Vol. 50; no. 12; p. 1343
• Main Author: Lipp, R
• Format: Journal Article
• Language: English
• Published: England 01.12.1998
• Subjects: Administration, Cutaneous; Crystallization; Drug Delivery Systems; Drug Interactions; Drug Stability; Drug Storage; Estradiol - chemistry; Excipients - chemistry; Norpregnenes - chemistry; Povidone - chemistry; Progesterone Congeners - chemistry; Solubility
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.1998.tb03357.x

The purpose of this study was to stabilize transdermal drug-delivery systems (TDDS) highly loaded with sex steroids against recrystallization of drugs during storage. To facilitate the selection of potential crystallization inhibitors a drug-excipient interaction test was also established. Analysis of the thermal behaviour of 1:1 steroid-excipient mixtures by differential scanning calorimetry (DSC) revealed that oestradiol and gestodene interact strongly with silicone dioxide and povidones, e.g. povidone K12. The addition of povidone K12 to polyacrylate-based matrix TDDS containing either 3% oestradiol or 2% gestodene resulted in stable systems which did not recrystallize during storage at 25 degrees C for more than 5 years. Significant recrystallization was, on the other hand, observed in non-stabilized reference patches even after 1 to 2 months storage. The DSC screening model proved very effective for selection of inhibitors of the crystallization of sex steroids in matrix TDDS. The crystallization inhibitor approach is a highly versatile stabilization tool for matrix patches containing high concentrations of sex steroids.