Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison of the supercritical antisolvent process with the conventional film method

Abstract

Pankaj Ranjan Karn,1 Su-Eon Jin,2 Benjamin Joon Lee,1,2 Bo Kyung Sun,1,2 Min-Soo Kim,3 Jong-Hyuk Sung,1,2 Sung-Joo Hwang1,2 1Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Yeonsu-gu, Incheon, Republic of Korea; 3College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea Objectives: The objectives of this study were to prepare cyclosporin A (CsA)-containing proliposomes using the supercritical antisolvent (SAS) process and the conventional thin film method for the comparative study of proliposomal formulations and to evaluate the physicochemical properties of these proliposomes.Methods: CsA-containing proliposomes were prepared by the SAS process and the conventional film method, composed of natural and synthetic phospholipids. We investigated particle size, polydispersity index, and zeta potential of CsA-containing proliposomes. In addition, both production yield and entrapment efficiency of CsA in different proliposomes were analyzed. Physicochemical properties of CsA-containing proliposomes were also evaluated, using differential scanning calorimetry and X-ray diffraction. The morphology and size of ­CsA-containing proliposomes were confirmed, using scanning electron microscopy. We checked the in vitro release of CsA from CsA-containing proliposomes prepared by different preparation methods, comparing them with Restasis® as a positive control and the stability of SAS-mediated proliposomes was also studied.Results: CsA-containing proliposomes formed by the SAS process had a relatively smaller particle size, with a narrow size distribution and spherical particles compared with those of conventionally prepared proliposomes. The yield and entrapment efficiency of CsA in all proliposomes varied from 85% to 92% and from 86% to 89%, respectively. Differential scanning calorimetry and X-ray diffraction studies revealed that the anhydrous lactose powder used in this formulation retained its crystalline form and that CsA was present in an amorphous form. Proliposome powders were rapidly converted to liposomes on contact with water. The in vitro release study of proliposomal formulations demonstrated a similar pattern to Restasis®. The SAS-mediated CsA-containing proliposomes were stable on storage, with no significant changes in particle size, polydispersity index, and entrapment efficiency.Conclusion: These results show promising features of CsA-containing proliposomal formulations, using the SAS process for the large-scale industrial application. Keywords: proliposomes, cyclosporin A, supercritical antisolvent process, thin film method, Restasis®