Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method

A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.7 μm, column using a buffer consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL min−1 and the detection wavelength was 210 nm. The limit of detection (LOD) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06 μg mL−1, respectively. The limit of quantification (LOQ) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 μg mL−1, respectively. This method was validated with respect to linearity, accuracy, precision, specificity and robustness. The method was also found to be stability-indicating

A Validated Stability Indicating RP-HPLC Method for the Determination of Aprepitant in Bulk and Pharmaceutical Dosage Forms

A stability indicating HPLC assay method has been developed and validated for the estimation of aprepitant in bulk and pharmaceutical dosage forms. A RP-HPLC isocratic separation was achieved on C18 column (250X4.6 mm i.d., 5µm) utilizing a mobile phase comprising of methanol and water in the ratio of 90: 10(v/v) and the eluents from the column were detected using a variable wavelength detector at 220 nm. The stress testing of aprepitant was carried out under acidic, alkaline hydrolysis, oxidation and thermal degradation (dry heat) conditions and apripitant was well resolved from its degradation products with good resolution. The proposed method has permitted the quantification of aprepitant in the linearity range of 1-100µg/ml and the flow rate was maintained at 1ml/min. The column was maintained at ambient temperature and the complete separation was achieved for aprepitant with all degradation products in an overall analytical run time of approximately 15 min and it was eluting at approximately 4.4 min. The retention times of aprepitant and rimonabant hydrochloride (IS) were found to be 4.383 min and 5.783 min, respectively. The limit of detection and limit quantification were found to be 0.130µg/ml and 0.395µg/ml, respectively. The percentage recovery was found to be in between 99.56 to 101.5 and the % RSD of system and method precision was found to be 1.20 and 0.561, respectively. The percentage amount of marketed commercial brand of aprepitant was found to be 99.97. The method was found to be suitable for the routine quality control analysis of aprepitant in bulk drug and formulation as well as for the stability indicating studies. The method was validated as per ICH guidelines

Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction

Purpose: To synthesize Schiff bases of 2-aminothiophenes and evaluate their anticonvulsant activity and in silco propertiesMethods: 2-Amino-N-o-tolyl-5,6-dihydro-4H-cylcopenta[b]thiophene-3-carboxamide was synthesized using 1,1,3,3-tetramethylguanidine lactate as a basic catalyst and by microwave irradiation. 2- substitued-o-tolyl-5,6-dihyro-4H-cylcopenta[b]thiophene-3-carboxamide was prepared by reacting with different substituted aromatic aldehydes. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against maximum electroshockinduced seizure (MES), and pentylenetetrazole-induced seizure (PTZ) against phenytoin and diazepam as reference standards. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions.Results: Among the 21 synthesized compounds, 2b, 2d, 2f, 2k, 2m, 2n and 2o showed good to moderate activity against MES and PTZ-induced convulsions. Compounds 2b, 2d, 2f, 2k and 2m exhibited lower activity against PTZ than against MES model while compounds 2n and 2o afforded greater protection against PTZ than against MES model. In silico results also revealed maximum binding affinity to GABA-AT protein which was higher than other compoundsConclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.Keywords: Ionic liquid, 2-Aminothiophenes, Anticonvulsant, In silco studies, Molecular docking

A New Validated Liquid Chromatographic Method for the Determination of Loratadine and its Impurities

An improved gradient, reversed-phase liquid chromatographic (RP-LC) method was developed and subsequently validated for the determination of Loratadine and its impurities/degradation products in pharmaceutical drug substance. Separation was achieved with Inertsil ODS-3V, 250 × 4.6 mm, 5μ column with gradient elution at a flow rate of 1.0 mL min−1. UV detection was performed at 220 nm. The described method is linear over a range of LOQ (0.044, 0.088, 0.084, and 0.072 μg mL−1 for impurity-B, impurity-C, impurity-D, and impurity-E respectively) to 1.2 μg mL−1 (0.6 μg mL−1 of the specification limit) for all the impurities and degradation products. The recovery of impurities were found to be in the range of 85–115 %. The method is simple, selective, and accurate for the quantification of impurities and degradation products of Loratadine in its bulk drug samples

Method Development and Validation of Montelukast in Human Plasma by HPLC Coupled with ESI-MS/MS: Application to a Bioequivalence Study

A simple, sensitive, and specific LC-ESI–MS/MS method for quantification of Montelukast (MO) in human plasma using Montelukast-d6 (MOD6) as an internal standard (IS) is discussed here. Chromatographic separation was performed on YMC-pack pro C18, 50 x 4.6 mm, S-3 μm column with an isocratic mobile phase composed of 10mM ammonium formate (pH 4.0):acetonitrile (20:80 v/v), at a flow-rate of 0.8 mL min−1. MO and MOD6 were detected with proton adducts at m/z 586.2→568.2 and 592.3→574.2 in multiple reaction monitoring (MRM) positive mode respectively. MO and MOD6 were extracted using acetonitrile as precipitating agent. The method was validated over a linear concentration range of 1.0–800.0 ng mL−1 with correlation coefficient (r2) ≥ 0.9996. The intraday precision and accuracy were within 1.91–7.10 and 98.32–99.17. The inter-day precision and accuracy were within 3.42–4.41% and 98.14–99.27% for MO. Both analytes were found to be stable throughout three freeze-thawing cycles, bench top, and autosampler stability studies. This method was utilized successfully for the analysis of plasma samples following oral administration of MO (5 mg) in 31 healthy Indian male human volunteers under fasting conditions

Design and synthesis of 1-aroyl-2-ylidene hydrazines under conventional and microwave irradiation conditions and their cytotoxic activities

We report the design and synthesis of 1-aroyl-2-(alkenyl/aryl)idene hydrazines as hybrid molecules derived from mefenamic acid and substituted hydrazones. A number of compounds based on this new scaffold were prepared in good yields. The key intermediate N-acylhydrazine, prepared from mefenamic acid, was coupled with a variety of aldehydes under conventional as well as microwave irradiation conditions. The second approach, that requires short reaction time, can be carried out under a solvent free condition and does not require the use of an acid catalyst or solid support. Some of the compounds synthesized showed cytotoxic activities in vitro

Synthesis of N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B

The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated CC bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies

Preparation and pharmacokinetic studies of mucoadhesive oral multiple unit systems of metronidazole

The objective of the present study was to investigate the applicability of matrix type chitosan treated alginate multiple unit systems (MUS) for sustained release of metronidazole prepared by ionotropic gelation method. Spherical MUS with 0.64 ± 0.95 to 0.75 ± 0.38 mm length and 0.63 ± 0.34 to 0.74 ± 0.28 mm breadth and 71.60 ± 0.42 to 82.15 ± 0.35 % entrapment efficiency were produced. The fluoroscopic study reveals that the MUS was retained in gastrointestinal tract (GIT) for more than 5 h and found to be distributed throughout the GIT. The in vivo evaluation in healthy human volunteers of the MUS and that of Flagyl® IR tablets each containing 400 mg drug revealed that the MUS showed improved pharmacokinetic parameters to Flagyl® producing a significantly different (p < 0.05) AUC. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver metronidazole and expected to be less irritant to gastric and intestinal mucosa.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and gastrointestinal transit evaluation of mucoadhesive oral Multiple Unit Systems of Furazolidone

The objective of present study was to improve gastric residence time of furazolidone by preparing mucoadhesive Multiple Unit Systems (MUS) with chitosan, Hydroxypropyl methyl cellulose K4M and sodium carboxymethyl cellulose by employing ionotropic gelation method. The resultant MUS were evaluated in vitro and in vivo. The particle size length ranged between 0.76 ± 0.25 to 0.89 ± 0.23mm, while the breadth was 0.76 ± 0.15 to 0.89 ± 0.06 mm, respectively. Encapsulation efficiency was in range of 82 to 90 %. MUS exhibited good mucoadhesive property in in vitro wash-off test. Stability studies showed no significant change in dissolution profiles (P < 0.05). The Gastrointestinal transit time was determined by fluoroscopic study which revealed that, the MUS retained in gastrointestinal tract for more than 5 hours and distributed throughout GIT. Based upon these results, prepared mucoadhesive MUS can be a good alternative to single unit systems to deliver Furazolidone with improved gastric residence time to treat intestinal amoebiasis.Colegio de Farmacéuticos de la Provincia de Buenos Aire