Acipimox Preparation And Evaluation Of Osmotic Pump

Acipimox is a derivative of nicotinic acid. It can decrease the level of blood fats obviously and no obvious adverse reactions were seen. It is suitable for typeⅡA,ⅡB,Ⅲ,ⅣandⅤhyperlipidemic patient, especially for hyperlipidemia with diabetic, gout and coronary heart disease patients.In this paper, acipimox was selected as model drug to prepare once daily bi-layer osmotic pump tablets(BOPT). Then, pharmacokinetic study of acipimox BOPT was performed in six dogs. The precise and reliable UV and HPLC method were established for analysis of acipimox BOPT in vitro and in vivo, which provided a basis for the further studies of pharmaceutics and pharmacokinetics in dogs.In the preparation of acipimox BOPT, polyethylene oxide(PEO)and sodium chloride were used as core tablet materials, cellulose acetate(CA)and polyethylene glycol 4000(PEG4000) were used as membrane materials, and acetone was used as solvent. Similarity factor (f2) was used as evaluation standerd. Formulation of drug layer, push layer, coating membrane, arts in preparation of tablets core, dissolution condition in vitro were investigated to discuss the different kind of factors on the release behavior of BPOP. Based on single-factor experiments, the weight of PEO, the weight of sodium chloride in drug layer, the weight of coating were selected as considerable factors, and the percentages of in vitro cumulative releases at 12h(Q), the lineanty(R2)of the release curve were selected as dependent variables. And central composite design-response surface methodology was used to optimize the formulations of BPOP. The results showed that, the optimal formulation had an excellent zero-order release profile and reproducibility in batches.Using the acipimox capsules as reference, relative bioavailability and pharmacokinetic study of self-made acipimox BOPT tablets were performed in six dogs by crossovered design, drug concentration in plasma of dogs after single dose oral administered of two dosage forms was detected by HPLC method. The results showed that: the AUC0-24of two dosage preparations were 115.5±6.807,112.0±23.76μg·h/ml respectively; The Cmax were 13.95±1.068,37.35±6.140μg/ml respectively; Tmax were 6.333±1.367,2.500±0.5478h respectively. Relative bioavailability of BOPT to acipimox capsules was 103.2%. Between acipimox capsules and self-made osmotic pump tablets, the Cmax of acipimox BOPT was lower than that of capsule, Tmax was longer than that of capsule. It is indicated that the self-made acipimox BOPT has better efect. With the method of Wagner-Nelson, the in vitro and in vivo correlation of self-made osmotic pump tablets was also studied. The results showed that acipimox BOPT had good correlativity between in vitro release and in vivo absorption.