FORMULATION, DEVELOPMENT AND IN VITRO EVALUATION OF TRAMADOL EXTENDED RELEASE TABLETS

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO). Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics. Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism. Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied

FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF ALENDRONATE BUCCAL TABLETS

The aim of this work was to develop a mucoadhesive buccal tablet for the buccal delivery of the alendronate via buccal mucosa. Buccal tablets of alendronate are designed to release drug at mucosal site for extended period of time without wash out of drug by saliva. Alendronate sodium is a bisphosphonates which has antiresorptive effect which is implicated in the prophylaxis and treatment of osteoporosis. Sodium alginate, ethyl cellulose and carbopol were selected as mucoadhesive polymers on the basis of their matrix forming properties. The objective of the study is to improve the bioavailability of alendronate buccal tablets. Extensive literature survey was done for the collection of theoretical and technical data. The methodology part includes the explanation of implemented methods in the present study. In present study, an attempt was made to design mucoadhesive buccal tablets containing alendronate, sodium alginate, ethyl cellulose and carbopol using as polymers. The tablets were prepared by direct compression method. The formulations were evaluated for hardness, thickness, friability, weight variation, drug content estimation, surface pH determination, swelling index, in vitro drug release. In vitro bioadhesive strength & in vitro release studies showed that formulation F11 showed optimum bioadhesive & exhibited optimum drug release 97.6% in 7hr. Kinetics results reveals that the F11 formulation follows zero order kinetics as correlation coefficient (r2) values are higher than that of first- order release kinetics.Optimized formula F11 show drug is released by non-Fickian diffusion mechanism. The stability studies of formulation F11 prepared mucoadhesive buccal tablets of alendronate were stable. Overall evaluations of the mucoadhesive of tablets show good mucoadhesive properties

DEVELOPMENT, CHARACTERIZATION AND PHARMACOKINETIC EVALUATION OF OPTIMIZED VILDAGLIPTIN SUSTAINED RELEASE MATRIX TABLET USING BOX-BEHNKEN DESIGN

Objective: The principal objective of this research was to develop and optimize cost-effective sustained-release Vildagliptin (VLN) tablets using the wet granulation method. Methods: The tablets were prepared by the non-aqueous wet granulation method. A Box-Behnken design was used to study the effect of the independent variables, i.e., HPMC K100 M, Eudragit RSPO and PVP K30, on the dependent variables swelling index, in vitro drug release at 8 and 12 h. The drug's physiochemical properties were investigated using ultraviolet (UV), Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC). The hardness, thickness, weight variation, content uniformity, swelling index, and in vitro drug release study of the formulated tablets were all evaluated. The optimized formulation Opt-VLD-SR was evaluated for pharmacokinetic parameters like AUC, Cmax, tmax and MRT. Results: The FTIR and DSC studies confirmed that no interaction occurred between the drug, polymers and excipients. The crystalline nature of VLN remained unchanged in the optimised formulation tablet, according to DSC studies. With the optimal concentration of both polymers, formulation Opt-VLN delayed drug release for up to 12 h. The formulated Optimized Sustained-release tablets (Opt-VLD-SR) showed significantly lower Cmax±3.01ng/ml) than conventional IR tablets (256.17±8.02ng/ml). In the pharmacokinetic study, the MRT for Optimized-VLD-SR is (7.40h) showed a better result than the Vildagliptin IR marketed product (3.70 h.), which leads to higher bioavailability of Vildagliptin.  Conclusion: Sustained release tablets of VLN with a combination of diffusion and erosion-controlled drug release mechanisms have been successfully developed

An gradient HPLC-DAD determination of phenylepherine, paracetamol, ambroxol and levocetrizine in pharmaceutical formulation

The development, validation and application of a simple and reliable gradient high-performance liquid chromatography–diode array detection (HPLC–DAD) procedure for the analysis of a complex mixture containing phenylephrine (PHE), paracetamol (PAR), ambroxol (AMB) and Levocetirizine (LEV) has been carried out . Chromatographic separation of PHE, PAR, AMB and LEV is achieved using a Phenomenex Ultracarb ODS-C18 (4.6×150 mm, 5 µ) column with gradient elution of the mobile phase composed of 10 mM phosphate buffer pH 3.3 and acetonitrile. A three step gradient program has been developed with step-1 elution starting with 2% (by volume) acetonitrile which ramped up linearly to 50% in 10 min, in step-2 reverting back to 20% in 5 min and in step-3 ended to achieve initial concentration of 2% in next 5 min thus contributing a total run time of 20 min. Flow rate maintained throughout the experiment is 1 mL/min. The Diode array detector (DAD) is set at 220 nm for quantification of the analytes based on measuring their peak areas. The retention times for PHE, PAR, AMB and LEV are approximately 4.4, 10.1, 14.00 and 17.90 min respectively. The proposed HPLC procedure is statistically validated with respect to linearity, ranges, precision, accuracy, selectivity and robustness. Calibration curves are found to be linear in 50 to 150% of target analyte in formulation with correlation coefficients > 0.9996. The validated HPLC method is applied successfully with good recoveries of analytes from tablet dosage; no interfering peaks were encountered from the inactive ingredients