Use of X-ray crystallography for the characterization of single crystals grown in steroid containing transdermal drug delivery systems

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 47; no. 2; pp. 133 - 138
• Main Authors: Lipp, Ralph, Müller-Fahrnow, Anke
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.1999; Elsevier Science
• Subjects: Administration, Cutaneous; Biological and medical sciences; Crystallization; Crystallography, X-Ray; Drug Delivery Systems; Drug Stability; Estradiol; Estradiol - administration & dosage; Estradiol - chemistry; General pharmacology; Gestodene; Medical sciences; Norpregnenes - administration & dosage; Norpregnenes - chemistry; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Transdermal drug delivery system; X-ray crystallography; X-ray crystallography; Gestodene; Transdermal drug delivery system; Estradiol; Short term; Stability; Transdermal system; Stabilization; Estrogen; Drug carrier; X ray; Crystallography; In vitro; Dosage form; Physicochemical properties; Structural analysis
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(98)00055-1

Target of the study was to characterize crystals which had grown in steroid-containing matrix patches during short-term storage and to thereby establish a rationale for the inhibition of crystal formation in those patches in general. Matrix type transdermal drug delivery systems (TDDS) containing either 2.2% gestodene or 3.3% estradiol were free of crystals directly after their production. However, crystals of up to 800 μm in length grew during 3 months of storage at ambient temperature. The application of several analytical methods did not help to identify the crystals. This was mainly due to the fact that the adhesive matrix surrounding the crystals could not be fully removed in the course of sample preparation with routine laboratory methods and thus impaired DSC, FTIR microscopy and hot stage polarized microscopy. However, within X-ray diffractometry, the residual amorphous patch matrix did not hamper the measurement of the crystals. Thus, they were identified as estradiol hemihydrate and gestodene form I, respectively. These results suggest that steroid-containing matrix TDDS should be stabilized against drug recrystallization e.g. by the addition of suitable crystallization inhibitors. Furthermore, systems containing estradiol may be stabilized by efficient removal water.