title: Development and validation of a HPLC method for dissolution and stability assay of liquid-filled cyclosporine capsule drug products.
abstract: To assay the dissolution samples of a drug product from several sources, a simple but broadly applicable analytical method is always desired. For the liquid-filled cyclosporine capsules, while analyzing the dissolution samples, the current compendial and literature HPLC methods have been found to be inadequate to provide satisfactory separation of the drug and the excipient peaks. Accordingly, a suitable isocratic reverse-phase HPLC method was developed for the analysis of dissolution samples of liquid-filled cyclosporine capsules. The method successfully separated the cyclosporine peak from the interfering chromatographic peaks of the excipients. The method was validated according to the ICH and FDA guidelines. Specificity, selectivity, linearity, accuracy, precision, and robustness were established over 3 days as part of method validation. Additionally, the degradation kinetics of cyclosporine in dissolution media was determined. Cyclosporine degradation followed a zero-order kinetics in the dissolution media with the respective rate constants of -3.5, -1.5, and -0.3%/h at 37°C, 25°C, and 10°C.
authors.affiliation: Division of Product Quality Research, OTR/OPS, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA. Xiaoming.Xu@fda.hhs.gov
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Abhay
authors.initials: A
authors.lastname: Gupta
authors.forename: Patrick
authors.initials: P
authors.lastname: Faustino
authors.forename: Pradeep M
authors.initials: PM
authors.lastname: Sathe
authors.forename: Vilayat A
authors.initials: VA
authors.lastname: Sayeed
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016572:Cyclosporine / Q000737:chemistry*; D007700:Kinetics; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002214:Capsules; D016572:Cyclosporine