Combined Dosage Form Research Articles

SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS DETERMINATION OF SULPHACETAMIDE SODIUM AND PREDNISOLONE ACETATE IN OPHTHALMIC FORMULATION

A simple, precise, accurate, and rapid derivative spectrophotometric approach for the simultaneous quantification of sulfacetamide sodium (SUL) and prednisolone acetate (PRE) in the combined dosage form has been established and validated. The wavelengths selected for analysis are 230 nm (ZCP of SUL) and 244 nm (ZCP of PRE) for SUL and PRE, respectively. The suggested technique has exhibited linearity for a concentration range of 2–6 µg mL-1 for PRE and 5–15 µg mL-1 for SUL, respectively. Both medications had percentage recoveries that varied from 99.41 to 101.8. The suggested approach has been validated according to ICH guidelines [Q2(R1)] for linearity, LOD, LOQ, accuracy and precision. The proposed method can be successfully utilized to analyze SUL and PRE concurrently in ocular formulations.

Stability Indicating HPLC Method for Simultaneous Assessment of Clopidogrel Bisulfate and Aspirin: Development and Validation

Objectives: The efforts were made to develop a HPLC analytical method for the simultaneous quantitative estimation of aspirin and clopidogrel and aim to identify and estimate the degradation of the drugs under the various stress conditions recommended by ICH guideline. Materials and Methods: The separation of two drugs were done by using LC-20AD liquid chromatograph having SPD-20A UV-vis detector on C18 (4.6 x 150 mm) column which was connected with loop 20μl and with HPLC-Dell system. Mobile phase consisted of acetonitrile: buffer in the ratio of 350:650 v/v. Flow rate was 1.3 ml/min and detection were done at 220 nm. Proportions of solvents and adjustment of mobile phase was carried out by screening. Results: The chromatographic separation of aspirin was noted at 4.299 minutes with average USP tangent of 8332.046 and clopidogrel was at 12.706 min with average of 11886.0397 tangent. A linear correlation was observed between concentration of aspirin and clopidogrel with their dilutions i.e r2 = 0.9986 and 0.9996 respectively. The outcome of study, with limit of detection 0.058 and 0.078 μg/ml and limit of quantification 0.117 and 0.156 μg/ml, for aspirin and clopidogrel revealed the repeatability, reproducibility and robustness of the method. Stability indicating parameters were tested by ICH guideline. Conclusion: It is concluded that the method is linear, reproducible, robust, rugged and stability-indicating for simultaneous calculation. It can be used as a routine quality control method for combined pharmaceutical dosage form and for its kinetic studies.

Oral Bioactive Self-Nanoemulsifying Drug Delivery Systems of Remdesivir and Baricitinib: A Paradigmatic Case of Drug Repositioning for Cancer Management.

Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.

Liquid chromatographic method for simultaneous estimation of anti‐hypertensive drug combination Azilsartan Medoxomil and Cilnidipine

AbstractA combination of Azilsartan Medoxomil and Cilnidipine is prescribed in the treatment of Hypertension. An accurate and precise high‐performance liquid chromatographic method has been developed for the estimation of Azilsartan Medoxomil and Cilnidipine in a combined tablet dosage form. Symmetry C18 (250 × 4.6 mm, 5 μm) column was used as the stationary phase, and methanol:water (85:15 v/v; pH 3.5) was used as the mobile phase. The method was linear in the concentration range of 4–20 μg/ml for Azilsartan Medoxomil and 1–5 μg/ml for Cilnidipine with a correlation coefficient (r2) 0.995 for Azilsartan Medoxomil and 0.995 for Cilnidipine. The proposed method was validated with respect to linearity, accuracy, precision, and robustness as per International Council on Harmonization Q2 (R1) guideline. A forced degradation study was performed to find out the intrinsic stability of the molecules. The degradation products were well resolved from the drug peak and did not interfere with the analysis. The method was successfully applied for the analysis of Azilsartan Medoxomil and Cilnidipine in combined tablet formulation.

Development and validation of stability indicating UPLC method for the simultaneous estimation of triamterene and hydrochlorothiazide in combined dosage forms using quality by design approach

BackgroundAccording to the information gathered from the literature, no technique for UPLC of triamterene and hydrochlorothiazide employing QbD in the formulations has been published. The technique development by incorporating QbD and validating for accuracy, linearity, precision, LOQ, LOD, ruggedness and selectivity as per ICH is part of the work’s modernity.ResultsScreening investigations led to the selection of cmps. Peak tailing was evaluated as a metric of technique robustness based on these important analytical attributes, namely retention time. With a 0.1 percent OPN: methanol (40:60) mobile phase, a flow rate of 0.3 ml/min, a wave length of 224 nm, an injection volume of 41, and a run time of 6 min, the best chromatographic separation was attained.ConclusionsThe method was verified using ICH criteria, which ensure a high level of linearity, accuracy, precision, specificity and robustness. As a result, the suggested approach is regarded as a quick and accurate method for estimating triamterene and hydrochlorothiazide at the same time.

Dissolution Method development and validation for simultaneous determination of Metformin and Teneligliptin in pharmaceutical tablets

We have developed and validated an inexpensive, selective, simple, and precise HPLC-RP dissolution method for estimating the concentration of Metformin and Teneligliptin in combination dosage form. This experimental analysis was performed on a reverse phase high performance high-performance liquid chromatography, (RP-HPLC) column (250mm x 4.6mm, 5µm) by using Mobile phase Acetonitrile and Potassium Dihydrogen Phosphate with concentration 0.05 M and buffer with pH-7.0 at a flow rate of 1.0ml/min and the detected at wavelength 225nm. In line with ICH guidelines, the linearity of the analytical method was discovered to be in the range of 7.0 to 21.00g/ml for Metformin. The linearity of the method for Teneligliptin was 22.5-67.5g/ml. Metformin and Teneligliptin had correlation coefficients greater than 0.990. The relative standard deviation value for system precision and method was less than 2.0%. All statistical data proves validity of the method and can be used for routine analysis of pharmaceutical dosage form.

Simultaneous Resolution of Clopidogrel Bisulphate and Aspirin in their Combined Dosage Form by Ratio First Derivative Spectrophotometry

Simultaneous Resolution of Clopidogrel Bisulphate and Aspirin in their Combined Dosage Form by Ratio First Derivative Spectrophotometry

Simultaneous Estimation of Abacavir Sulfate and Lamivudine in their Combined Dosage Form by First Derivative Zero-Crossing and Ratio First Derivative Spectroscopic Methods

Simultaneous Estimation of Abacavir Sulfate and Lamivudine in their Combined Dosage Form by First Derivative Zero-Crossing and Ratio First Derivative Spectroscopic Methods

HPTLC-Densitometric Estimation of Anti-hypertensive Drug Combination Azilsartan Medoxomil and Cilnidipine in Combined Dosage Form

A combination of Azilsartan Medoxomil and Cilnidipine is prescribed in the treatment of Hypertension. The present work represents an accurate and precise high-performance thin layer chromatographic method for the estimation of Azilsartan Medoxomil (AZL) and Cilnidipine (CLN) in combined tablet dosage form. Pre-coated silica gel- G60 F254 aluminum sheet (100 × 100 mm, 0.2 mm layer thickness) were used as stationary phase and Ethyl Acetate: Toluene: Glacial Acetic Acid (5: 4.9: 0.1 %v/v/v) in the mixture was used as mobile phase. The method was linear in the concentration range of 200 - 2000 ng/band for AZL and 50 -500 ng/band for CLN with a correlation coefficient (r2) of 0.996 for AZL and 0.999 for CLN. The proposed method was validated with respect to linearity, accuracy, precision, and robustness as per ICH Q2 (R1) guideline. A forced degradation study was performed to assess the stability indicating the nature of the method. All the degradant peaks were well resolved from the peak of the drug without any interference. The method was successfully applied for the analysis of AZL and CLN in combined tablet formulation.

A Review on Methods Developed for Estimation of Paracetamol in Combination with Other Drugs

In this ever-growing world, it is crucial to improve upon the formulations in terms of potency, patient acceptability, fewer side effects, and quicker relief. Due to these requirements, the market is flooded with various combination dosage forms, with a constant increase in number. Paracetamol is a commonly used non-steroidal anti-inflammatory drug (NSAID) that has antipyretic and analgesic action. This drug is available in a wide range of combinations. It acts by inhibiting the production of pr

Rapid HPLC determination of ciprofloxacin, ofloxacin, and marbofloxacin alone or in a mixture

A simple, sensitive, and accurate chromatography (RP-HPLC) method for simultaneous estimation of Ciprofloxacin, Ofloxacin, and Marbofloxacin in their combined pharmaceutical dosage form or individually. The HPLC separation was achieved on a Hypersil (C18, 150 mm × 4.6 mm, 5 μm particle size) analytical column or equivalent. A mixture of triethanolamine (1 %), acetonitrile (80 %), and water was used as the mobile phase, with a flow rate of 1.2 mL /min and a detector wavelength of 280 nm at ambient temperature. In the HPLC method, the retention times of Ciprofloxacin, Ofloxacin, and Marbofloxacin were found to be 1.854, 2.480, and 4.688 min, respectively, and linearity was obtained in the range of 25–80 µg/mL for Ciprofloxacin, Ofloxacin, and Marbofloxacin. The correlation coefficient for the method was greater than 0.999. The RP-HPLC method validation parameter lay within its acceptance criteria as per the ICHq2 (R1) guideline. Hence, it can be successfully used for routine analysis of Ciprofloxacin, Ofloxacin, and Marbofloxacin in raw material or pharmaceutical dosage forms.

A Validated RP-HPLC Method Development and Validation for The Simultaneous Estimation of Nebivolol and Valsartan in Bulk Drug and Pharmaceutical Dosage Form

A novel, simple, accurate and rapid Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method has been developed and validated for the determination of Nebivolol and Valsartan in bulk and tablet dosage form. Gradient elution chromatography has been developed on C18 column (5µm, 4.6mm* 250mm) with a mobile phase consist of pH 4 acetonitrile,water and Methanol (25:35:40) with a flow rate of 1ml/min at detection of 270 nm wavelength. The retention time for Nebivolol and Valsartan was found to be 4.59 and 10.2 respectively. Chromatography parameters were validated as per ICH guidelines and the method can be applicable for routine quantitative analysis of drugs in combined dosage form.

Simultaneous HPLC determination of Metronidazole, Lidocaine and Miconazole in a combined intravaginal semi solid dosage form

Simultaneous HPLC determination of Metronidazole, Lidocaine and Miconazole in a combined intravaginal semi solid dosage form

Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form

Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form

Development and validation of stability indicating thin‐layer chromatography methods for simultaneous estimation of Bisoprolol Fumarate and Hydrochlorothiazide

AbstractFor the simultaneous estimation of Bisoprolol Fumarate and Hydrochlorothiazide in combined pharmaceutical dosage form, a simple, selective, rapid, and precise stability indicating high‐performance thin‐layer chromatography method has been developed and validated.The proposed high‐performance thin‐layer chromatography technique includes the usage of high‐performance thin‐layer chromatography plates (Merck) pre‐coated with silica gel 60F254 on aluminum sheets and a cellular segment comprising of methanol:acetonitrile (8:2, v/v). The densiometric measurement of both drugs was performed in the absorbance mode at 223 nm. The method has been used to accurately estimate Bisoprolol Fumarate and Hydrochlorothiazide in a combined tablet dosage form. Both the drugs had been subjected to acid‐alkali hydrolysis, photolytic, thermal, and oxidation degradation and each of them had been discovered to be prone to acid‐alkali hydrolysis, photolytic, thermal, and oxidation degradation. The developed stability‐indicating analytical method was validated. The various validation parameters checked are linearity, inter‐day and intra‐day precision, robustness, accuracy, and so forth.The degradation products obtained were well resolved from the pure drugs with significantly different Rf values. The method can be utilized for stability‐indicating analysis since it successfully separates the drug from its degradation products. The method was successfully validated and validation results are within the acceptable range of International Council for Harmonization guidelines.

Evaluation of the Formulation of Combined Dosage Form of Albendazole and Mebendazole through In vitro Physicochemical and Anthelmintic Study

In the current study, the combination of albendazole and mebendazole was analyzed as a potential anthelmintic agent against Lumbricus terrestris (commonly known as earthworms). The in vitro analysis showed the combination of 400 mg albendazole and 300 mg mebendazole had more significant therapeutic activities (mean paralysis time 58 minutes and mean death time 97.33 minutes) than the others. Then the combinations were formulated as tablet using different ratios of excipients where formulation-D performed excellent flow properties (Carr’s index: 14.04±0.27, Hausner’s ratio: 1.19 ± 0.03, Angle of repose: 40.22 ± 0.73). The dosage form prepared from formulation-D had better hardness of 9.40 ± 0.34 kg-N and loss of weight of 0.003 mg compared to other formulations. In terms of disintegration and dissolution studies, formulation-D exhibited excellent properties. The tablet was disintegrated fully within 8.94 ± 0.37 minutes in phosphate buffer (pH 8.3) and dissolution analysis showed R2 of 0.995 for albendazole and 0.991 for mebendazole which were statistically significant. The postformulation anthelmintic study showed that the prepared tablet dosage form was therapeutically effective because it paralyzed and killed all the earthworms within 56 and 85 minutes, respectively. Finally, the tablet was subjected to the scanning electron microscopy (SEM) analysis which confirmed better surface morphology and drug-drug compatibility within the dosage form. The next stage of the work will focus on in vivo analysis for market preparation. Dhaka Univ. J. Pharm. Sci. 21(2): 153-163, 2022 (December)

A Simple and Validated Stability Indicating HPLC Method for Simultaneous Quantification of Brimonidine, Timolol and Benzalkonium Chloride in Anti-Glaucoma Ophthalmic Formulations

The combined dosage form of brimonidine, timolol and benzalkonium chloride is prescribed for lowering intraocular pressure in patients with ocular hypertension. As no analytical HPLC method reported for the estimation of brimonidine, timolol and benzalkonium chloride together in ophthalmic formulations, the present study was aimed to fulfill the gap identified in literature. The separation of analytes was achieved on Cosmosil C18 (250 × 4.6 mm; 5 μ id) as stationary phase, pH 4.3 acetate buffer and methanol in 30:70 (v/v) as mobile phase at 1.0 mL/min and UV detection at 227 nm. In this condition, well resolved, retained peaks were identified at 3.11 min for brimonidine, 4.86 min for timolol and 5.57 min for benzalkonium chloride. The method reports 0.5, 1.25 and 0.0125 μg/mL, respectively for brimonidine, timolol and benzalkonium chloride as LOD, which proves that the method have enough sensitivity levels for the detection analytes in samples. The method passes all the validation parameters as per the guidelines proved that the method was valid. The method shows less % degradation in various stress studies such as acidic, base, peroxide, thermal and UV light conditions and can effectively separate various stress degradation compounds and confirms the stability indicating nature of the method. The method applicability was assessed by analyzing the drug content in Combigan® ophthalmic drops and method reports the assay of 98.92%, 99.36% and 98.46% for brimonidine, timolol and benzalkonium chloride, respectively. Based on the results, it can be concluded that the method can adequately suitable for the separation and quantification of brimonidine, timolol and benzalkonium chloride and hence can be applicable for the routine analysis of brimonidine, timolol and benzalkonium chloride in ophthalmic formulations.

Application of Box-Behnken design for optimization of A RP-HPLC method for determination of palonosetron and netupitant in their combined dosage form in presence of their impurities

The use of (Netupitant and Palonosetron) combination to treat nausea and vomiting in cancer chemotherapy patients has been authorized by the Food and Drug Administration. For the simultaneous determination of Netupitant (NET) and palonosetron (PAL) in the presence of two of their related substances and in their dosage form, a sensitive and selective RP-HPLC method has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method’s analytical parameters. It employed RP-HPLC with a UV detector. Waters ODS-C18 column (3.5 µm, 75 × 4.6 mm) with a mobile phase composed of acetonitrile: 25 mM phosphate buffer (pH = 3.5) in a gradient mode at 254 nm was employed to separate the cited drugs and their impurities. Palonosetron was linear over the concentration range (1–50 µg/mL) and Netupitant (10–100 µg/mL). According to ICH guidelines, the new method underwent thorough validation. Between the proposed method’s results and those from the reported method, there was no significant difference. It is easy to apply the technique to the analysis of the specified drugs in their combination dosage form for quality control considerations.

Application of Box-Behnken experimental design and response surface methodology for selecting the optimum RP-HPLC conditions for the simultaneous determination of methocarbamol, indomethacin and betamethasone in their pharmaceutical dosage form

An isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined dosage form using an Inertsil ODS-3v C18 (250 × 4.6 mm, 5 μm) column with UV- detection at 235 nm. Experimental design using Box-Behnken design (BBD) was applied to study the response surface during method optimization and to achieve a good separation with a minimum number of experimental runs. The three independent parameters were pH of buffer, % of acetonitrile and flow rate of the mobile phase while the peak resolution of IND from MTL and the peak resolution of BET from IND (R2) were taken as responses to obtain mathematical models. The composite desirability was employed to optimize a set of responses overall (peak resolutions). The predicted optimum assay conditions include a mobile phase composition of acetonitrile and phosphate buffer (pH 5.95) in a ratio of 79:21, v/v, pumped at a flow rate of 1.4 mL min−1. With this ideal condition, the optimized method was able to achieve baseline separation of the three drugs with good resolution and a total run time of less than 7 min. The linearity of MTL, IND, and BET was determined in the concentration ranges of 5–600 µg mL− 1, 5–300 µg mL− 1, and 5–300 µg mL− 1 and the regression coefficients were 0.9994, 0.9998, and 0.9998, respectively. The average percent recoveries for the accuracy were determined to be 100.41 ± 0.60%, 100.86 ± 0.86%, and 100.99 ± 0.65% for MTL, IND, and BET, respectively. The R.S.D.% of the intra-day precision was found to be less than 1%, while the R.S.D.% of the inter-day precision was found to be less than 2%. The RP-HPLC method was fully validated with regard to linearity, accuracy, precision, specificity, and robustness as per ICH recommendations. The proposed method has various applications in quality control and routine analysis of the investigated drugs in their pharmaceutical dosage forms and laboratory-prepared mixtures with the goal of reducing laboratory waste, analysis time, and effort.

A brief Review on Q-absorption Ratio Method in UV-Spectrophotometry

This present work carries a brief review on Q-Absorption ratio method in UV-spectrophotometry. Absorption ratio method is used for the ratio of the absorption at two selected wavelengths one of which is iso-absorptive point and other being the λmax of one of the two components. The aim of this article is to give brief idea about various method developed using Q-Absorption ratio methodon combined dosage forms. It shows selection of wavelength, linearity study and choosing solvent for give combine dosage form. This study also gives brief idea about practical and industrial application of Q-Absorption ratio method.