Optimization of empagliflozin immediate release tablets (10 mg) using central composite rotatable design with response surface methodology.

Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.

Empagliflozin: HPLC based analytical method development and application to pharmaceutical raw material and dosage form.

The current investigation is based on efficient method development for the quantification of empagliflozin in raw and pharmaceutical dosage forms, as no pharmacopoeial method for the drug is available so far. The developed analytical method was validated as per ICH guidelines. C18 column with mobile phase (pH 4.8) consisted of 0.1% trifluoroacetic acid solution and acetonitrile (70:30 v/v) was used for drug analysis. The calibration plot showed good linear regression (r2>0.999) over the concentration of 0.025-30 µg mL-1. The LOD and LOQ were found to be 0.020 µg mL-1 and 0.061 µg mL-1, respectively. The percentage recovery was estimated between 98.0 to 100.13%. Accuracy and precision data were found to be less than 2%, indicating the suitability of method for routine analysis in pharmaceutical industries. Moreover, the drug solution was found to be stable in refrigerator and ambient room temperature with mean % accuracy of >98%. Empagliflozin contents were also tested in both the raw API and marketed tablet brands using this newly developed method. The mean assay of raw empagliflozin and tablet brands were ranged from 99.29%±1.12 to 100.95%±1.69 and 97.18%±1.59 to 98.92%±1.00 respectively. Based on these findings, the present investigated approach is suitable for quantification of empagliflozin in raw and pharmaceutical dosage forms.