Optimization of prescription of ambroxol hydrochloride sandwich osmotic pump tablets by Box-Behnken design-response surface method / 中国药学杂志

ABSTRACT

OBJECTIVE: To optimize the formulation of ambroxol hydrochloride sandwich osmotic pump tablets using Box-Behnken design response surface method. METHODS: Firstly, significant factors, including amount of glucose, ratio of pore former to weight of coating, and thicknesss of coating, were chosen carefully by single-factor methods, then Box-Behnken design-response surface method was adopted to understand the effects of these factors on the drug release by using similarity factor f2 as evaluation index. And multiple linear regression model and quadratic polynomial equation were established to evaluate the relationship between these factors and similarity factor f2. Secondly, the permeation mechanism of sandwich osmotic pump was studied carefully by SEM and drug release behavior investigation. RESULTS: The quadratic polynomial equation was ideal to fit the prediction result of drug release; the optimal formulation according to Design-Expert8.0.5 software was established as follows 50 mg of glucose, 8% of pore former, 9% of coating weight. The f2 was approximate 89.33 compared with ideal drug release curve, which was relatively close to the model-predicted f2 value (88.89). Through investigation of permeation mechanism, it was found that the drug release from this delivery system was driven by osmotic pressure difference between the interior of tablets and the release medium. By means of SEM observation, it was shown that some pores on the coating surface were produced after drug release in the medium, but few before drug release, which cued that a lot of medium got into the interior of tablets through the tunnels formed by the porogen in the coating. CONCLUSION: Box-Behnken design method can be used to optimize the formulation of sandwich osmotic pump tablets.