Statistical Design and Optimization of Sustained Release Formulations of Pravastatin

The objective of the current study was to formulate a sustained release (SR) formulation for pravastatin. Pravastatin is a lipid lowering, biopharmaceutical classification class-III agent.

SR tablets of pravastatin were prepared using variable amounts of hydroxy methyl propyl cellulose (HPMC) K4M and sodium carboxy methyl cellulose in various proportions by direct compression in a 3² factorial design. The amounts of the polymers HPMC K4M and sodium carboxy methyl cellulose required to obtain prolonged release of drug were chosen as independent variables, X₁ and X₂, respectively, whereas times taken for 10%, 50%, 75%, and 90% drug release were chosen as dependent variables.

Nine formulations were developed and were checked using pharmacopoeial tests. The results showed that all the factorial batches were within the standard limits. The dissolution parameters of all formulations were subjected to kinetic fitting and various statistical parameters were determined. Polynomial equations were developed and verified for dependent variables. Formulation F₅, containing 25 mg of HPMC K4M and 25 mg of sodium carboxy methyl cellulose, was the formulation most similar (similarity factor f₂=89.559, difference factor f₁=1.546) to the marketed product (Pravachol).

The best formulation (F₅) follows Higuchi's kinetics and non-Fickian diffusion zero order kinetics (n=1.083).