Once daily controlled release matrix tablet of Prochlorperazine maleate: Influence of Ethocel^® and/or Methocel^® on in vitro drug release and bioavailability

Abstract

Context: Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance.

Methods: Tablet formulations F1, F2 and F3 based on different concentrations of Methocel^® K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel^® K100 LV-CR Premium and Ethocel^® Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil^® tablet was conducted on rabbits, using HPLC-UV system at λ_max 254 nm.

Results: The test tablet, containing 28% Methocel^® and 58% Ethocel^® (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel^® content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-C_max (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t_1/2 (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R² = 0.8458) between drug absorbed in vivo and drug released in vitro.

Conclusions: The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Keywords::

• Dry granulation-slugging method
• bioequivalence
• in vivo-in vitro correlation
• Prochlorperazine
• polymers

Acknowledgments

We are obliged to the M/S Colorcon, Asia Pacific; Ltd. India for generously providing gift samples of the Methocel^® K100LV-CR Premium and Ethocel^® Standard 7FP Premium. We are also thankful to M/S Bryon Pharmaceuticals, Peshawar for providing their manufacturing facilities and to Prof. Dr Gul Majeed Khan, Dean Faculty of Pharmacy, Gomal University; DIK for providing his Lab facilities to conduct physicochemical tests on the tablets manufactured.

Declaration of interest

We are obliged to the Authorities of University of Peshawar for providing partial financial support. We, the authors hereby report no declaration of interest.