Selection and use of crystallization inhibitors for matrix-type transdermal drug-delivery systems containing sex steroids.
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.
Drug-Delivery Systems, Schering AG, Berlin, Germany.
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D000279:Administration, Cutaneous; D003460:Crystallization; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004355:Drug Stability; D004356:Drug Storage; D004958:Estradiol / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D009652:Norpregnenes / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D045167:Progesterone Congeners / Q000737:chemistry*; D012995:Solubility
D005079:Excipients; D009652:Norpregnenes; D045167:Progesterone Congeners; C033273:Gestodene; D004958:Estradiol; D011205:Povidone