Design and Evaluation of Bilayer Pump Tablet of Flurbiprofen Solid Dispersion for Zero-Order Controlled Delivery

J Pharm Sci. 2018 May;107(5):1434-1442. doi: 10.1016/j.xphs.2017.12.026. Epub 2017 Dec 29.

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: PVP VA64; central composite design-response surface methodology; flurbiprofen; hot-melt extrusion; osmotic pump; solid dispersion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Delayed-Action Preparations / chemistry*
  • Drug Compounding / methods
  • Drug Stability
  • Flurbiprofen / administration & dosage*
  • Flurbiprofen / chemistry
  • Osmosis
  • Pyrrolidines / chemistry*
  • Solubility
  • Tablets
  • Temperature
  • Transition Temperature
  • Vinyl Compounds / chemistry*

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Pyrrolidines
  • Tablets
  • Vinyl Compounds
  • poly(vinylpyrrolidone-co-vinyl-acetate)
  • Flurbiprofen