Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design

Abstract

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer–Peppas model, (Adj-R² = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

Keywords::

• DOE
• hidroxypropylmethyl cellulose
• polyethylene glycol

Acknowledgments

The authors would like to thank to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for the financial support; Colorcon for the polymers supply; Dr. Helvécio Rocha (Farmanguinhos/Fiocruz – RJ) for primaquine diphosphate supply; Dr. Juliano de Morais for the very kind help in reviewing the text.

Declaration of interest

The authors report no conflicts of interest.