Optimization of Formulation Variables and Predictability Study of Hydrophilic Matrix Based Sustained Release Tablet of Nitroglycerin using Response Surface Methodology

Аннотация

The aim of this work was to develop and statistically optimize nitroglycerin matrix tablets for sustained release application by response surface methodology based on 3² full factorial design utilizing a polynomial equation. The tablets were manufactured using direct compression technology with 2% w/w nitroglycerin in lactose as the active ingredient and different levels of hydrophilic polymers, i.e. Methocel^® K15M (X₁) and Methocel^® K100LV (X₂) as independent variables, along with other requisite excipients. The cumulative percentages of drug released at 1, 2, and 4 h were selected as dependent variables and restricted to 27-32% (Y₁), 45-50% (Y₂), and 65-70% (Y₃), respectively. In vitro dissolution testing was conducted using United States Pharmacopeia (USP) apparatus 1 (basket) and samples were analyzed using a validated reversed-phase high performance liquid chromatographic (RP-HPLC) method. The quadratic model fitted to the data well was used to predict the responses in the optimal region (p<0.05). Based on factorial design, different nitroglycerin release profiles, dissolution time (t_25%, t_50%, and t_80%), and mean dissolution time (MDT) were obtained. The observed responses of the optimized formulation, containing 47.54 mg Methocel^® K15M and 23.61 mg Methocel^® K100LV, were coincided well with the predicted values by the experimental design. Furthermore, it provided a dissolution pattern which was very similar to the commercial product, where the calculated values of difference factor (f₁) and similarity factor (f₂) were 3.03 and 83.78, respectively, and followed anomalous (non-Fickian) diffusion mechanism.

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