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.

ÖZAmaç: Bu çalışmanın amacı tamsulosin hidroklorür ve solifenasin süksinatın aynı anda miktar tayininin yapılabilmesi için basit bir senkronize spektroflorimetri yöntemi geliştirmek ve valide etmektir. Gereç ve Yöntemler: Bahsedilen analitlerin aynı anda miktar tayinlerinin yapılabilmesi için birinci türev senkronize spektroflorimetri yöntemi kullanılmıştır. Tamsulosin hidroklorür 322 nm de ölçüm yapılarak (bu dalga boyu solifenasin süksinatın sıfır kesim noktasıdır) solifenasin süksinat ise 570 nm de ölçüm yapılarak (bu dalga boyu tamsulosin hidroklorürün sıfır kesim noktasıdır) miktar tayinleri gerçekleştirilmiştir. Bulgular: Kalibrasyon eğrileri tamsulosin hidroklorür için 2-10 μg/mL, solifenasin süksinat için ise 30-150 μg/mL konsantrasyon aralığında hazırlanmıştır. Geliştirilen yöntemle; ICH kılavuzlarına göre hesaplanan doğrusallık, seçicilik, doğruluk, kesinlik ve LOD ve LOQ değerleri kullanılarak başarılı sonuçlar elde edilmiştir. Önerilen yöntemle yapılan analiz sonuçları ticari formülasyon içerisinde tamsulosin hidroklorürün %95.0 solifenasin süksinatın ise %103.5 oranında bulunduğunu göstermiştir. Bu sonuçlar preparatın üzerinde belirtilen değerler ile iyi bir uygunluk göstermektedir. Sonuç: Önerilen analitik yöntemin tablet dozaj formlarında tamsulosin hidroklorür ve solifenasin süksinatın rutin kontrol analizlerinde kullanılabileceği anlaşılmıştır. Anahtar kelimeler: Tamsulosin hidroklorür, solifenasin süksinat, senkronize spektroflorimetri, yöntem validasyonu Objectives: The present study was undertaken with the objective to develop and validate a simple spectrofluorimetric method for the simultaneous quantification of tamsulosin hydrochloride and solifenacin succinate. Materials and Methods: First-derivative synchronous spectrofluorimetry was attempted for the simultaneous quantification of the analytes. Tamsulosin hydrochloride was quantified at a wavelength of 322 nm (zero-crossing wavelength point of solifenacin succinate) and solifenacin succinate was measured at 570 nm (zero-crossing wavelength point of tamsulosin hydrochloride). Results: Calibration plots were constructed over the concentration range of 2-10 μg/mL for tamsulosin hydrochloride and 30-150 μg/mL for solifenacin succinate. The method gave satisfactory results when it is validated for linearity, specificity, accuracy, precision, LOD and LOQ as per the ICH guidelines. The assay values in the commercial formulation were found to be in the percentage range of 95.0 for tamsulosin hydrochloride and 103.5 for solifenacin succinate by the proposed method. These results were well in agreement with their label claim. Conclusion:The proposed synchronous analytical method can be employed for routine quality control analysis of tamsulosin hydrochloride/ solifenacin succinate in tablet dose forms.

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