Development and Validation of a HPLC Method for Dissolution and Stability Assay of Liquid-Filled Cyclosporine Capsule Drug Products

Abstract

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 liquidfilled 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.

Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution

“…The quantification of CyA was performed utilizing an HPLC-UV system with a Zorbax Eclipse Plus reverse phase C-18 column (dimension 4.6 × 250 mm, 5 μm) (Agilent Technologies Santa Clara, USA), thermostated at 68 °C. The mobile phase used was an 80:20 (v/v) mixture of acetonitrile and HPLC grade water using a flow rate of 1 mL/min . The injection volume used was 20 μL, and absorbance was monitored at 210 nm.…”

Development of an Analytical UHPLC Method for the Estimation of Cyclosporine in SMEDDS and Protein Binding

“…But the types of structural changes have been undetected in polypeptide structure of CyA. Various reports suggest that high temperature leads to the conformational changes of CyA (Zaghloul, Burckart et al 1986, Xu, Gupta et al 2013, Szerkus, Wolska et al 2014. Therefore, high temperature is a critical factor for the LC-UV analysis of CyA.…”

“…Blood sample determination of patients for CyA is very critical because of individual variations in absorption, distribution, metabolism and elimination processes (Jaklitsch, Monger et al 1998, Mika andStepnowski 2016). CyA has very low water solubility (6.6μg/mL) at 37°C, as a consequence it suffers from low oral bioavailability as dissolution is a limiting factor for absorption (Xu, Gupta et al 2013). CyA is marketed in various dosage forms in order to overcome its solubility and dissolution associated absorption e.g.…”

Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres

“…The samples were replenished with fresh media. CsA was quantified by HPLC-UV using a Kinetex Õ C 18 column (4.6 Â 100 mm, Phenomenex, Macclesfield, UK) based on a modified method described previously 25 . The acetonitrile/water (50:50 v/v) mobile phase was pumped at a flow rate of 1 ml/min with a sample injection volume of 20 ml.…”