Analysis Of Combined Dosage Form Research Articles

Development and Validation of a Solvent Extraction UV Spectrophotometric Method for the Estimation of Rosuvastatin Calcium and Telmisartan in Combined Dosage Form

A simple, precise, accurate and reproducible method has been developed and validated for the estimation of Telmisartan and Rosuvastatin Calcium in their combined tablet dosage form using solvent extraction method followed by UV spectrophotometry. The absorbance was measured at 243.8nm and 295.3nm for Rosuvastatin and Telmisartan respectively. Linearity was found over the concentration range 5-25 micro gram per ml. The solvents used for the estimation were methanol for Telmisartan and phosphate buffer for Rosuvastatin. The method was statistically validated for accuracy, precision, linearity, LOD and LOQ according to ICH guidelines and can be used for analysis of combined dosage form as well as for the individual drugs.

Chemometrics-Assisted Spectrophotometric Method Development and Validation for Simultaneous Estimation of Emtricitabine, Tenofovir Alafenamide Fumarate, and Dolutegravir Sodium in Dosage Form

Aim: This study aims on the development of a chemometric-assisted spectroscopic method for the analysis of combined dosage form of emtricitabine (EMT), tenofovir alafenamide fumarate (TEN), and dolutegravir sodium (DOL). The use of a multivariate algorithm to analyse spectrophotometric data is a novel approach to estimating drug concentrations in formulations. Materials and Methods: The quantitative estimation of EMT, TEN, and DOL in tablets was carried out using four chemometric approaches: Classical least square (CLS), inverse least square, partial least square, and principal component regression. Thirty-two ternary mixtures of calibration sets and 16 mixtures of validation sets were prepared. The absorbance data matrix was attained by calculating absorbance at 25 different wavelengths in a range of 240–336 nm (Δλ = 4 nm). The chemometric calculations were performed using Matlab2018a and Minitab software. The developed methods were validated. Results: The great accuracy of the current study was justified by the near-perfect recovery values (100%) and low standard deviation. For chemometrics approaches, the root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP), and root mean square error of cross-validation (RMSECV) outcomes display decent accuracy and precision. Conclusion: The CLS approach yielded the lowest predicted residual error sum of squares, RMSEC, RMSEP, and RMSECV scores. As a result, CLS might be regarded as the best chemometric approach among all techniques utilized. The label claim determined is in excellent accordance with the mean recoveries for EMT, TEN, and DOL. So, it can be used in quality control laboratories.

RP-HPLC Accelerated Degradation Method Development and Validation for Determination of Amlodipine and Atorvastatin in Combination Dosage Form of Tablet

Abstract: Aim: The Cost effective, Accurate, Precise Accelerated degradation method has been developed for determination of Atorvastatin and Amlodipine in combination dosage form of tablet and validated as directed by ICH guidelines. Objectives: To develop and validate analytical method which can be easily adoptable in frequent analysis of Amlodipine and Atorvastatin combinations in the laboratories. Materials and Methods: The 0.02 M potassium dihydrogen phosphate: acetonitrile: methanol (30:10:60 v/v/v) was used as mobile phase and pH 4 adjusted using ortho phosphoric acid at flow rate 1.0 ml/min. The column used for method development was Octadecylsilane-C18 (5 μm, 25 cm × 4.6mm, i. d.). The peaks obtained in the chromatogram were well resoluted. The scanning wavelength used was 244 nm with PDA detector. Results: The linearity for both the drugs was found between 05 - 30 μg/ml for both drugs with regression coefficient equation 0.995 and 0.999 at retention time 8.32 min and 11.09 min for Amlodipine and Atorvastatin respectively. The results obtained were statistically validated as directed by ICH guidelines and was found satisfactory. Conclusion: The developed and validated method was found to be very specific, accurate and precise. It can be utilized for routine analysis of combined dosage form of Amlodipine and Atorvastatin in the laboratory. Key words: Amlodipine, Atorvastatin, RP-HPLC, ICH Guidelines, PDA Detector, Validation.

Implementation of QRM and DoE-Based Quality by Design Approach to VEER Chromatography Method for Simultaneous Estimation of Multiple Combined Dosage Forms of Paracetamol

Paracetamol is a well-known OTC drug, and several combinations are available in the market. The numbers of chromatography methods were published for analysis of combined pharmaceutical dosage form of paracetamol. But every combination needs separate and dedicated chromatography condition for analysis. Hence, a chromatography method was developed for simultaneous estimation of some combined pharmaceutical dosage form of paracetamol using QRM and DoE-based quality by design approach. Quality risk management (QRM) was done by method risk parameter identification and assessment. The eleven potentially critical method risk parameters were screened for their main effect on the resolution of peaks by Placket Burman design. Further, three critical method risk parameters were analysed for their effect on the resolution of peaks by Box–Behnken design. Method operable design region (MODR) was navigated for optimisation of chromatography method. The chromatography method was used for simultaneous estimation of six combined dosage forms of paracetamol with different drugs. After QRM and DoE, mobile phase composition, the volume of acid, and plate activation temperature were found to be critical method parameters and optimised by the navigation of MODR. The optimised method gave results of the assay in agreement with the labelled claim of the dosage form. The developed method can fulfil a requirement of six different chromatography methods for the analysis of combined dosage forms of paracetamol. Hence, the developed chromatography method is versatile, economical, eco-friendly, and robust (VEER) for the simultaneous analysis of six combined dosage forms of paracetamol.

Development of a Discriminative and Biorelevant Dissolution Test Method for Atorvastatin/Fenofibrate Combination with Appliance of Derivative Spectrophotometry.

Nowadays, the market is flooded with combinations of drugs in various dosage forms, but there is a lack of official methods to quantify them. A single dissolution test method for the analysis of combined dosage form is preferred for simplification of quality control testing. If the developed dissolution medium mimics the biorelevant and discriminating dissolution procedure for drug products with limited drug aqueous solubility it is a useful tool for qualitative forecasting of the in vivo behavior of formulations. Dissolution profiles were evaluated for atorvastatin and fenofibrate in capsules, using a paddle-type United States Pharmacopeia dissolution apparatus in 900 mL of medium at 50 rpm and 37±0.5°C. The best medium was 900 mL of 0.5% w/v sodium lauryl sulfate. The cumulative % dissolution was more than 85% within 45 min for marketed tablets. The proposed dissolution test conditions have discriminative power, dissimilarity factor (f1) values are low (12-16%), and similarity (f2) factor values are also low (45-48%). Hence the use of 0.5% w/v sodium lauryl sulfate solution is justified. The dissolution method was validated (% relative standard deviation <2). To quantify both drugs simultaneously, a second derivative spectrophotometric method was established (λmax 281 nm and 296 nm, respectively, for atorvastatin and fenofibrate) in acetate buffer, pH 2.8 solution.

Development of dissolution test method for a telmisartan/amlodipine besylate combination using synchronous derivative spectrofluorimetry

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.

Simultaneous Estimation of Pregabalin and Methylcobalamine in Pharmaceutical Formulation by RP-HPLC Method

A simple, precise, rapid, selective, and economic reversed phase high-performance liquid chromatography (RPHPLC) method has been established for simultaneous analysis of PRG and MC. A Phenomenex C18 (250×4.6 mm i.d) chromatographic column equilibrated with mobile phase water: methanol (60:40 v/v) adjusted to pH 6.5 with Triethylamine (1% v/v) was used. Mobile phase flow rate was maintained at 1 ml/min and effluents were monitored at 218 nm. The sample was injected using a 20 μl fixed loop, and the total run time was 10 min. Experimental conditions such as pH of mobile phase, column saturation time, selection of wavelength, etc. were critically studied and the optimum conditions were selected. The calibration curve 50-300 μg/ml for PRG and 0.5-2.0 μg/ml for MC. The limit of quantification was 24.10 μg/ml for PRG and 0.40 μg/ml for MC respectively. This HPLC procedure is economic, sensitive, and less time consuming than other chromatographic procedures. It is an importance tool for analysis of combined dosage form.

Simultaneous Estimation of Pregabalin and Methylcobalamine in Pharmaceutical Formulation by HPTLC-Densitometry Method

A simple, precise, rapid, selective, and economic reversed phase high-performance thin layer chromatography (HPTLC) method has been established for simultaneous analysis of PRG and MC. HPTLC method was developed using on precoated silica gel F254 G60 plates as stationary phase, using methanol:toluene:ammonia (30%) (8:2:0.4 v/v/v) as mobile phase. The plates were scanned at approximately 497 nm for both PRG and MC respectively. In HPTLC method both the drugs were resolved using proposed mobile phase and Rf value was found to be 0.60 for PRG and Rf 0.33 for MC. The method was found to linear in the range 1500-7500 ng/band for PRG, 150-750 ng/ band based for MC respectively. This HPTLC procedure is economic, sensitive, and less time consuming than other chromatographic procedures. It is important tool for analysis of combined dosage form.

Simultaneous Estimation of Ambroxol Hydrochloride and Doxofylline in Pharmaceutical Formulation by HPTLC-Desitometric Method

A simple, precise, rapid, selective, and economic reversed phase high-performance thin layer chromatography (HPTLC) method has been established for simultaneous analysis of Ambroxol Hydrochloride and Doxofylline. The HPTLC method was performed on precoated silica gel G60 F254 plates with Diethyl ether:n-butanol:Ammonia (9:0.9:0.1 v/v/v) as mobile phase. The plates were developed in a 7.0 cm at ambient temperature. The developed plates were scanned and quantified at their absorption at approximately 254 nm for AMB and DOX. The drugs were satisfactorily resolved with Rf 0.29 ± 0.02 for and Rf 0.56 ± 0.02 for DOX. The calibration plot was linear between 100- 600 ng /band for AMB and 200-1200 ng/band based for DOX. This HPTLC procedure is economic, sensitive, and less time consuming than other chromatographic procedures. It is a user-friendly and importance tool for analysis of combined dosage form.

Simultaneous Estimation of Metformin Hydrochloride and Repaglinide in Pharmaceutical Formulation by HPTLC-Densitometry Method

A simple, precise, rapid, selective, and economic reversed phase high-performance liquid chromatography (HPTLC) method has been established for simultaneous analysis of Metformin Hydrochloride and Repaglinide. HPTLC method was developed using on precoated silica gel G60 F254 plates as stationary phase, using methanol:ammonium sulphate (0.25%) (pH-5.7) (2.5:7.5, v/v) as mobile phase. The plates were scanned at approximately 243 and 236 nm for HPLC and HPTLC both respectively. In HPTLC method both the drugs were resolved using proposed mobile phase and Rf value was found to be 0.34 for MET and Rf 0.60 for REPA. The method was found to linear in the range 500-2500 ng/band for MET, and 100-500 ng/band based for REPA respectively. This HPTLC procedure is economic, sensitive, and less time consuming than other chromatographic procedures. It is a user-friendly and importance tool for analysis of combined dosage form.

Simultaneous HPTLC determination of rabeprazole and itopride hydrochloride from their combined dosage form

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75±0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.