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Design and evaluation of controlled onset extended release multiparticulate systems for chronotherapeutic delivery of ketoprofen

Author(s): HN Shivakumar1, Sarasija Suresh2, BG Desai1
1 Department of Pharmaceutical Technology, K. L. E. S's College of Pharmacy, Rajajinagar 2nd Block, Bangalore-560 010, India 2 Department of Pharmaceutics, Al-Ameen College of Pharmacy, Hosur Road, Bangalore-560 027, India

Correspondence Address:
H N Shivakumar Department of Pharmaceutical Technology, K. L. E. S's College of Pharmacy, Rajajinagar 2nd Block, Bangalore-560 010 India E-mail:

An oral controlled onset extended release dosage form intended to approximate the chronobiology of rheumatoid arthritis is proposed for site-specific release to the colon. The multiparticulate system consisting of drug-loaded cellulose acetate cores encapsulated within Eudragit S-100 microcapsules was designed for chronotherapeutic delivery of ketoprofen. Drug-loaded cellulose acetate cores were prepared by emulsion solvent evaporation technique in an oily phase at different drug:polymer ratios (1:1, 2:1 and 4:1). These cores were successfully microencapsulated with Eudragit S-100 following the same technique at the core:coat ratio of 1:5. Scanning electron microscopy (SEM) revealed that the cellulose acetate cores were discrete, uniform and spherical with a porous and rough surface, whereas the Eudragit microcapsules were discrete and spherical with a smooth and dense surface. In vitro drug release studies of the Eudragit microcapsules were performed in different pH conditions following pH-progression method for a period of 16 h. The release studies indicated that the microcapsules posses both pH-sensitive and controlled-release properties, showing limited drug release below pH 7.0 (6.40 to 8.94%), following which the cellulose acetate cores effectively controlled the drug release for a period of 11 h in pH 7.5. The differential scanning calorimetric and powder X-ray diffraction studies demonstrated that ketoprofen was present in dissolved state in the cellulose acetate polymeric matrix, which could explain the controlled drug release from the cores. The release of ketoprofen from Eudragit microcapsules in pH 7.5 depended on the cellulose acetate levels and was characterized by Higuchi's diffusion model.

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