New analytical quality by design-oriented HPLC method with multiple response optimization (Derringer’s desirability function) was demonstrated for simultaneous analysis of three antidiabetic drugs (metformin hydrochloride/empagliflozin/linagliptin) in a fixed-dose combination. Central composite design was employed for systematic optimization of critical method parameters, namely, % organic phase (X1), aqueous phase pH (X2) and flow rate (X3) while resolution, capacity factor and theoretical plate number as critical analytical attributes. Effective chromatographic separation of title analytes was accomplished on Std. Discovery C18 column at 30°C with mobile phase comprising acetonitrile: phosphate buffer pH 5 (38:62% v/v), pumped at a flow rate of 1 mL/min by isocratic elution pattern and UV detection at 222 nm. The model is rectilinear in the range of 1.0–200, 0.2–40 and 0.1–20 μg/mL at retention times of 3.04, 3.93 and 5.99 min for metformin, empagliflozin and linagliptin, respectively. The method obeyed all validation parameters of ICH Q2(R1) guidelines. The proposed HPLC method was highly robust for method transfer, regulatory flexibility within design space and can be used for assay of pharmaceutical dosage forms comprising these analytes. The proposed method was applied for stability studies of drugs under various stress conditions.

Aim: Current work entails the analytical quality by design (AQbD) based robust HPLC method for real-time analysis of canagliflozin and metformin. Different pKa values of two drugs made their chromatographic separation critical. Materials and Methods: The critical method parameters were systematically optimized using factorial experimental design (central composite design) and contours were generated as a function of significant variables when analyzed in the modeling software. The method operable design region that control the variation in response is obtained from contour plot and verified experimentally. Results: Effective chromatographic separation of title analytes was accomplished on SPOLAR C 18 (250 x 4.6 mm, 5µ) column at 25°C with mobile phase comprising of phosphate buffer, pH 6.0 and acetonitrile (55:45 % v/v), pumped at a flow rate of 0.8 mL/ min by isocratic elution pattern and UV detection at 254 nm. The linear model was established in the range of 50-300 and 5-30 and µg/mL at retention times of 3.24 and 10.77 min for metformin and canagliflozin, respectively. Conclusion: Method obeyed all validation parameters of ICH Q2 (R1) guidelines and able to discriminate the Adduct generated upon drug degradation. The proposed method was pertinent for assay drugs and extended to quantify the drugs in prevalence of biological matrix.

Purpose: To develop and validate a dissolution test method for tablets containing 80 mg of drotaverine hydrochloride (DRT) and 250 mg of mefenamic acid (MEF DRT and MEF combination tablets.

Background Analytical quality by design driven HPLC method has been optimized for simultaneous estimation of dapagliflozin and saxagliptin in pharmaceutical dosage form. Response surface methodology was employed for optimization of experimental conditions using three factors such as organic phase (%), pH of aqueous phase, and flow rate of mobile phase. Results Virtuous separation of analytes was achieved with mobile phase consisted of acetonitrile: phosphate buffer, pH 5.8 (26:74% v/v) with flow rate 0.96 mL/min using SPOLAR C18 column (250 × 4.6 mm, 5 μ) with run time 6 min and UV detection at 236 nm. Retention time for dapagliflozin and saxagliptin were found to be 3.5 and 5.0 min, respectively. Method was validated as per ICH guidelines. The plot between peak area vs concentration for dapagliflozin and saxagliptin were rectilinear in the range of 0.2-300 μg/mL and 0.1-150 μg/mL respectively with detection and quantification limits were 0.061 and 0.18 μg/mL for dapagliflozin and 0.014 and 0.043 μg/mL for saxagliptin, respectively. Conclusion The proposed method was exploited for assay, in vitro dissolution, and stability studies of target drugs in marketed dosage form.

The dissolution process is considered an important in vitro tool to evaluate product quality and drug release behavior. Single dissolution methods for the analysis of combined dosage forms are preferred to simplify quality control testing. The objective of the present work was to develop and validate a single dissolution test for a telmisartan (TEL) and amlodipine besylate (AML) combined tablet dosage form. The sink conditions, stability and specificity of both drugs in different dissolution media were tested to choose a discriminatory dissolution method, which uses an USP type-II apparatus with a paddle rotating at 75 rpm, with 900 mL of simulated gastric fluid (SGF without enzymes) as the dissolution medium. This dissolution methodology provided good dissolution profiles for both TEL and AML and was able to discriminate changes in the composition and manufacturing process. To quantify both drugs simultaneously, a synchronous first derivative spectrofluorimetric method was developed and validated. Drug release was analyzed by a fluorimetric method at 458 nm and 675 nm for AML and TEL, respectively. The dissolution method was validated as per ICH guidance.Uniterms: Combined dosage forms/quality control. Dissolution test/combined dosage forms. Telmisartan. Amlodipine besylate. Spectrofluorimetry/quantification analysis.O processo de dissolução é considerado como uma importante ferramenta in vitro para avaliar a qualidade do produto e o comportamento de liberação do fármaco. Prefere-se um ensaio único de dissolução para formas farmacêuticas contendo associação de fármacos pela simplificação dos testes de controle de qualidade. O objetivo do presente trabalho foi desenvolver e validar um teste de dissolução único para forma farmacêutica comprimidos contendo telmisartana (TEL) e besilato de anlodipino (AML) associados. Condições "sink", estabilidade e especificidade de ambos os fármacos nos diferentes meios de dissolução foram avaliadas para selecionar um método de dissolução discriminatório, que utiliza um aparato do tipo II da USP, com pás girando a 75 rpm e 900 mL de fluido gástrico simulado (SGF sem enzima) como o meio de dissolução. Estas condições proporcionaram bons perfis de dissolução para ambos, TEL e AML, sendo capaz de discriminar as mudanças na composição e processo de fabricação. Para quantificar os dois fármacos simultaneamente, um método de fluorescência derivada sincronizado foi desenvolvido e validado. A quantidade de fármaco liberado foi analisada pelo método fluorimétrico em 458 e 675 nm para a AML e TEL, respectivamente. O método de dissolução foi validado de acordo com a orientação da ICH.Unitermos: Forma farmacêutica com associação/controle de qualidade. Teste de dissolução/forma farmacêutica com associação. Telmisartana. Besilato de anlodipino. Espectrofluorimetria/análise quantitativa.