ABSTRACT
OBJECTIVE: To select excipients and optimize preparation for the ambroxol hydrochloride/levosalbutamol sulfate dry powder inhalation. METHODS: Drug and different excipients in the same ratio were prepared by spray drying to obtain a certain particle size as drug particles or carriers for dry powder inhalation, respectively. Study and compare the parameters of powders of the dry powder inhaler, such as the angle of repose, moisture content, and emptying rate, etc, to screen the excipient of the vectors. Afterward, Box-Behnken design method was adopted to optimize of preparation parameters. RESULTS: When lactose-high branched cyclodextrin compounds were used as composite carriers, their powder properties meet the requirements of dry powder inhaler, such as the repose angle was 39.69 degrees, the bulk density was 0.37 g·mL-1, the tap density was 0.66 g·mL-1, the evacuation rate of drug-carrier powders in capsules was 93.12%, and the water content was 0.10% and the simulated lung deposition rate was 14.63%. The preparation parameters, such as sample concentration, inlet air temperature, nozzle diameter parameters, theirs values were 50 mg·mL-1, 110℃, 1 mm, respectively, were opmized by Box-Behnken design method, which could obtain the carrier particle size of 30.33 μm. CONCLUSION: Lactose-high branched cyclodextrin complexes can be used as carrier for levosalbutamol sulfate-ambroxol hydrochloride compound dry powder inhaler, which could meet the requirements of dry powder inhaler by spray-drying preparation method.
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.
ABSTRACT
This paper reported that a new type of floating osmotic pump of ambroxol hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.