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Design and Evaluation of Bilayer Pump Tablet of Flurbiprofen Solid Dispersion for Zero-Order Controlled Delivery
Authors:Lizhen Cheng  Ting Li  Ling Dong  Xiaoyu Wang  Qiye Huo  Haoyu Wang  Zhujun Jiang  Xinyu Shan  Weisan Pan  Xinggang Yang
Affiliation:Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China
Abstract:In this study, a bilayer osmotic pump tablet of flurbiprofen (FP) solid dispersions (SDs) was developed to increase the solubility of the poorly soluble drug and controlled drug release at a constant rate. Based on the investigation of thermodynamic properties the drug, the carrier, and the calculation of the solubility parameters, the FP-SD was prepared by hot-melt extrusion technique with the povidone (PVP) VA64 carrier. Then, central composite design-response surface methodology was used to evaluate the influence of factors on the responses. Consequently, PVP VA64 was selected as the carrier for preparing FP-SD. The results of differential scanning calorimetry and X-ray confirmed that FP in FP-SD was in an amorphous state. FTIR indicated that the intermolecular hydrogen bond probably formed between FP and PVP VA64 in FP-SD. Correlation of release profiles to zero-order kinetics was significant (R2 = 0.9939). The mathematical models had good predictability because the deviation was less than 1% between the predicted value and measured value. These results demonstrated that FP-SD osmotic pump tablets successfully increased the solubility of FP and controlled the release of FP at a constant rate.
Keywords:flurbiprofen  PVP VA64  solid dispersion  hot-melt extrusion  osmotic pump  central composite design-response surface methodology
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