Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.
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-R(2) = 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.
Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. marceloduque@usp.br
Marcelo Dutra
MD
Duque
Rogério Nepomuceno
RN
Kreidel
Maria Elena Santos
ME
Taqueda
André Rolim
AR
Baby
Telma Mary
TM
Kaneko
Maria Valéria Robles
MV
Velasco
Vladi Olga
VO
Consiglieri
D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008747:Methylcellulose / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011319:Primaquine / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013607:Tablets / Q000737:chemistry
D003692:Delayed-Action Preparations; D010710:Phosphates; D013607:Tablets; D011092:Polyethylene Glycols; D008747:Methylcellulose; D011319:Primaquine