Preparation And In Vitro Dissolution Of Cyclosporine A Active Release Tablets

Cyclosporine A (CyA) is widely administered in the dosage forms of soft capsules, oral solutions and injections nowadays. However, significant intra and inter individual bioavailability differences due to bile induced pre self-emulsification in vivo, many adverse side effects due to the expicient Cremophor (CrEL), as well as fabrication complexity of soft capsules and unpleasant taste of oral solutions were observed. Due to its insolubility in water, the most common soild dosage forms of CyA are unavailable yet. The present research demonstrates a unique and easily fabricated active release tablet (ART) using solid dispersion technology, which involves dissolving CyA in melted lipid mixture of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) and Gelucire? 44/14, impregnating the CyA-lipid melt with colloidal silicon dioxide, solidifying the CyA-lipid-SiO2 mixture by cooling it to room temperature followed by grinding and sieving, and thereby using this obtained CyA solid dispersion to produce tablet with microcrystalline cellulose (MCC) and crospovidone (PVPP). The ART was optimized to achieve desired formulation and fabrication procedure. The dissolution profiles of CyA from ART were investigated and compared with those from control tablets (composed of all the ingredients except any lipid), CyA-lipid melt (loaded in capsules) and reference soft capsules respectively. Results showed that nearly 80% of CyA was released from ART within 30 min in water and had comparability in vitro release behavior to reference capsules. The drug was found in a micro-emulsion form in the final dissolution media with droplet size distribution below 250nm by Photon Correlation Spectroscopy (PCS) detection. Crystalline state evaluation of CyA in ART was conducted through powder x-ray diffraction (PXRD) and found that CyA might be in a molecular state in the tablet. A three month stability test of CyA ART was conducted by drug content determination, dissolution and PXRD tests and verified its stability. This research demonstrates a useful and simplified procedure to prepare CyA fast released tablet using active release technology and might be helpful to solve fast released formulation problems of other insoluble frugs.