Enhanced Bioavailability and Dissolution of Atorvastatin Calcium from Floating Microcapsules using Minimum Additives

• Published in: Scientia pharmaceutica 2012, Vol.80 (1), p.215-228
• Main Authors: Khan, Furquan Nazimuddin, Dehghan, Mohamed Hassan G
• Format: Article
• Language: English
• ISSN: 0036-8709; 2218-0532
• DOI: 10.3797/scipharm.1104-26

Atorvastatin calcium, a lipid-lowering drug, is much less bioavailable because of reduced solubility in acidic media. Multiple-unit floating microcapsules of Atorvastatin calcium (ATC) were developed to expand the gastric residence time of the drug, as ATC has maximum rate of absorption in the upper GI tract. Floating microcapsules were prepared by Emulsion-solvent evaporation technique through incorporation of dioctyl sodium sulphosuccinate (DSS) as a dissolution enhancer. The microcapsules were assessed for shape, size, drug entrapment efficiency, stability and in-vitro drug dissolution rate and were subjected to SEM, DSC and PXRD studies. The ATC-loaded floating microcapsules were spherical in shape and had the particle size of about 28.10 μm and drug-loading efficiency of about 96.55 %. The floating microspheres containing DSS had significantly higher drug dissolution rates than those without DSS. The best formulation, AT4, consisting of Ethyl cellulose, DSS and Poly Ox®, had a maximum drug dissolution rate of 97.86 %, as compared to Storvas 80 mg (Ranbaxy Ltd, as a reference) which had a rate of only 54% during a period of 12 h in acidic media. A pharmacokinetic study performed on albino rabbits illustrates that the bioavailability of AT4 floating microcapsules significantly increased to nearly 1.7 times that of Storvas 80 mg. The present study indicates that the use of multi-unit floating microcapsules for delivery of ATC can improve its bioavailability.