Abstract
The objectives of this study were to prepare push–pull osmotic tablets (PPOT) of felodipine using an interpolymer complex of chitosan (CS) and poly(acrylic acid) (PAA) as an osmopolymer, and to study the mechanisms of drug release from these tablets. The interpolymer complexes were prepared with different weight ratios of CS to PAA. Preparation of PPOT involved the fabrication of bilayered tablets with the drug layer, containing felodipine, polyethylene oxide, and the polymeric expansion layer, containing the CS–PAA complex. The effects of polymer ratios, type of plasticizers, and compression forces on release characteristics were investigated. It was found that drug release from PPOT exhibited zero-order kinetics and could be prolonged up to 12 or 24 h depending on the plasticizer used. PPOT using dibutyl sebacate showed a longer lag time and slower drug release than that using polyethylene glycol 400. In the case of polyethylene glycol 400, an increase in the CS proportion resulted in an increase in the drug release rate. The compression force had no effect on drug release from PPOT. Drug release was controlled by two consecutive mechanisms: an osmotic pump effect resulting in the extrusion of the drug layer from the tablet and subsequent erosion and dissolution of the extruded drug layer in the dissolution medium. The mathematical model (zero-order) related to extrusion and erosion rates for describing the mechanism of drug release showed a good correlation between predicted and observed values.
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ACKNOWLEDGMENTS
The authors are grateful to the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program for research funding (Grant no.PHD/0206/2545) and the Institute of Pharmaceutical Technology, University of Basel (Basel, Switzerland) for instrument support. Professor LA Damani is acknowledged for his help with scientific and editorial comments on manuscript.
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Ketjinda, W., Sinchaipanid, N., Limsuwan, P. et al. Development of Push–Pull Osmotic Tablets Using Chitosan–Poly(Acrylic Acid) Interpolymer Complex as an Osmopolymer. AAPS PharmSciTech 12, 132–140 (2011). https://doi.org/10.1208/s12249-010-9572-z
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DOI: https://doi.org/10.1208/s12249-010-9572-z