FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF BOSENTAN BY USING SYNTHETIC POLYMERS

Objective: Bosentan is an endothelin receptor antagonist (ERA) indicated for the treatment of Pulmonary arterial hypertension (PAH). The aim of the present study involves the development of sustained release matrix tablets of bosentan in order to release the drug in sustained and predictable manner. Methods: Bosentan SR Matrix tablets were prepared by Wet granulation method. The tablets were evaluated for Hardness, Thickness, Friability and Drug content and were subjected to a 12 hours in vitro drug release studies. Results: The amount of Bosentan released from the tablet formulations at different time intervals was estimated using a UV Spectroscopy method. Among all the formulations are prepared by using different polymers like HPMC K 4 M, HPMC K15 M at different ratios. Conclusion: We Can Conclude that Among the Ten formulations, F-2 formulation containing drug to HPMC K 4 M in ratio 1:0.5 is optimized based on its ability to sustain drug release till 12 hours of dissolution study, The results of the study clearly demonstrated that HPMC matrix tablet formulation is an effective and promising drug delivery system for once daily administration of Bosentan

DESIGN SYNTHESIS OF NOVEL ACRIDINE TAGGED PYRAZOLE DERIVATIVES AS AURORA KINASE INHIBITORS

Objective: A series of novel synthesis of 5-Substituted-3-phenyl-4,5-dihydro-pyrazole-1-carbothioic acid [4-(9, 10-dihydro-acridin-9-yl)-phenyl]- amide (IV) were synthesized using standard procedures and evaluated for cytotoxic studies. Methods: 9-(4-Chloro-phenyl)-9 and 10-dihydro-acridine (I) were formed by cyclization of diphenylamine with substituted acids in the prescience of zinc chloride and synthesis of 5-substituted-3-phenyl-4, 5-dihydro-pyrazole-1-carbothioic acid amide (3) by the cyclization of different chalcones (II) and final compounds were synthesized by fusion of 5-substituted-3-phenyl-4, 5-dihydro-pyrazole-1-carbothioic acid amide (III) with 9-(4-Chloro-phenyl)-9, 10-dihydro-acridine (I) by microwave irradiation method. Characterization of synthesized compounds by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopic methods. Obtained compounds were evaluated for their cytotoxicity against human breast cancer cell lines (MCF/wt) by sulforhodamine-B assay. Docking studies with Aurora kinase protein were performed to elucidate the possible mechanistic insights of these novel acridine tagged pyrazole derivatives. Results: Moderate to good in vitro cytotoxic potentials of the newly synthesized molecules was reported against selected human breast cancer cell lines. Among the tested molecules, compound C6 showed good cytotoxic activity against MCF/wt (08.2±0.4 μM). The dock scores of the tested compounds were ranged between −8.926 and −5.139. Compound C6 which has been reported as the most effective cytotoxic agent among the series also reported the highest dock score of -8.926 and showed hydrogen bond interaction with GLU-211, LYS-162, and LYS-143. Ligand binding energy with protein suggested compound C6 has shown the highest binding energy of −86.32133 kcal/mol. Conclusion: The in vitro studies of the newly synthesized acridine tagged pyrazole derivatives reported considerable cytotoxic potentials against human breast cancer cell lines and structure-activity relationship studies to suggest that acridine tagged pyrazole derivatives with hydroxy group present on phenyl ring at fifth position of pyrazole ring could probably increase the cytotoxic potentials. With the reported bioactivities of these derivatives, further studies on the derivatization could elucidate the broader cytotoxic potentials

Development of Extended Release Formulations of Ilaprazole Tablets

Extended release products are designed to release their medication in a controlled manner at a predetermined rate, duration, and location to achieve and maintain optimum therapeutic blood levels of a drug. The objective of the study is to formulate and evaluate Ilaprazole Controlled release tablets comparable to the innovator product. F1-F9 formulations were prepared using varying concentrations of super disintegrates like Crospovidone, Croscarmellose sodium and Sodium starch glycolate in different concentrations. Based on the hardness, friability, weight variation, drug content, F6 formulation was found to be optimised. The selected F6 formulation was sub coated with HPMC P 50 and followed by enteric coating with Acryl-EZE-80 (Eudragit L100-55). 3 formulations (F10-F12) were prepared by using coating. Among the three formulations, F11 formulation was found to be best. FTIR studies were carried out to find out drug and excipient compatibility studies, the studies revealed that there were no interactions. DSC studies also carried out to demonstrate any changes in physical forms of the drug molecule. Keywords: Ilaprazole, Extended release tablets, Crospovidone, Croscarmellose sodium, Sodium starch glycolate, HPMC P 50, Acryl-EZE-80

Comparative Study of Antihypertensive Drugs Amlodipine Besylate /Metoprolol Succinate and Nebivolol Hydrochloride /Valsartan Combinations in Bilayer Tablets

The present research is an approach to develop a formulation platform that shall help in minimizing the time and effort taken to develop a drug delivery system. Taking bilayer tablet technology as a representation for drug delivery system, well accepted antihypertensive drugs, Amlodipine besylate and Metoprolol succinate were considered as model drugs for the study. Initially the process variables like concentration of the disintegrants, Sodium starch Glycolate and cross carmellose sodium, Polymers HPMC K100M and K4M were standardized with these drugs so that the incorporation of a new combination drugs would provide predictable results with a minimal trial runs. Nebivolol hydrochloride and Valsartan were considered as test drugs since they are novel antihypertensive drug combination and their physicochemical and pharmacokinetic parameters were almost similar to that of the model drugs. The r value 0.98943 indicates a good correlation between the release profile of Amlodipine besylate (model drug) and Nebivolol hydrochloride (test drug) from the IR layer. Similarly, the r value in the range of 0.9998 indicates a good correlation between the release profile of Metoprolol succinate (model drug) and Valsartan (test drug) from the SR layer. The comparable experimental results of the model drugs and test drugs considered for this study infer that if two drugs are similar in their physicochemical and pharmacokinetic parameters, their behavior with respect to in vitro parameters will be similar provided formulation variables remains constant. This concept could be productive in developing drug delivery system for new drugs for which extensive research and time are major constraints. Keywords: Bilayer tablets, fixed unit dosage form, Amlodipine besylate, Metoprolol Succinate Nebivolol hydrochloride, Valsartan

SYNTHESIS, CHARACTERIZATION AND ANTI-INFLAMMATORY ACTIVITY OF NOVEL PYRAZOLE DERIVATIVES

Objectives: To synthesize novel pyrazole derivatives and their evaluation for anti-inflammatory activity. Methods: The synthesis of chalcone (1) was carried out by using Claisen-Schmidt condensation. which on further cyclization with thiosemicarbazidegives the substituted 3, 5-diphenyl-4, 5-dihydro-pyrazole-1-carbothoic acid amide (2), further reaction with different aldehydes yield title compounds(3). Using this scheme 8 compounds were synthesized which further have been evaluated for anti-inflammatory activity by egg-albumin induced pawedema.Results: All the synthesized compounds have been supported by spectral analysis. The anti-inflammatory activity of synthesized compounds wascompared with standard anti-inflammatory agent Diclofenac sodium.Conclusion: Compound-8, compound-2 and compound-3 showed greater anti-inflammatory activity due to the presence of alkene and electronwithdrawing groups (Cl and NO2). Keywords: Chalcone, Thiosemicarbazide, Pyrazole derivatives, Anti-inflammatory activity

Formulation and Evaluation of Bilayer Matrix Tablets of Nebivolol Hydrochloride and Valsartan

The present study is an attempt to develop bilayer matrix tablets of Nebivolol Hydrochloride and Valsartan with immediate release for Nebivolol Hydrochloride and sustained release for Valsartan. Superdisintegrants such as sodium starch glycolate and Crosscarmellose sodium were evaluated for immediate release of Nebivolol Hydrochloride and polymers HPMC K100M and K4M for sustained release of Valsartan. Preformulation studies were performed prior to compression. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content and in vitro drug release using USP dissolution apparatus type 2 in 0.01N HCl and phosphate buffer pH 6.8. All the pre and post compression parameters were found to be within the acceptable limits. The results of dissolution show that the formulations B3 was the best of all immediate and sustained release layer batches. The release kinetics of Valsartan was subject to curve fitting analysis in order to identify the best fit kinetic model. The regression analysis proves that the best formulations follow zero order release and drug release by diffusion process based on Fick’s law of diffusion. The data for stability studies infer no considerable change in drug content and dissolution rates as per ICH guidelines. The best formulation B3 was subjected to in vivo pharmacokinetic studies in rabbit model. In vitro, In vivo correlation (IVIVC) showed considerable linearity. Hence a novel bilayer tablet formulation of Nebivolol Hydrochloride and Valsartan was successfully developed by combining both immediate (IR) and sustained (SR) release layers. Keywords: Bilayer tablets, fixed unit dosage form, Nebivolol hydrochloride, Valsartan, LC-MS analysis

Studies on the antidiarrhoeal activity of Aegle marmelos unripe fruit: Validating its traditional usage

<p>Abstract</p> <p>Background</p> <p><it>Aegle marmelos </it>(L.) Correa has been widely used in indigenous systems of Indian medicine due to its various medicinal properties. However, despite its traditional usage as an anti-diarrhoeal there is limited information regarding its mode of action in infectious forms of diarrhoea. Hence, we evaluated the hot aqueous extract (decoction) of dried unripe fruit pulp of <it>A. marmelos </it>for its antimicrobial activity and effect on various aspects of pathogenicity of infectious diarrhoea.</p> <p>Methods</p> <p>The decoction was assessed for its antibacterial, antigiardial and antirotaviral activities. The effect of the decoction on adherence of enteropathogenic <it>Escherichia coli </it>and invasion of enteroinvasive <it>E. coli </it>and <it>Shigella flexneri </it>to HEp-2 cells were assessed as a measure of its effect on colonization. The effect of the decoction on production of <it>E. coli </it>heat labile toxin (LT) and cholera toxin (CT) and their binding to ganglioside monosialic acid receptor (GM1) were assessed by GM1-enzyme linked immuno sorbent assay whereas its effect on production and action of <it>E. coli </it>heat stable toxin (ST) was assessed by suckling mouse assay.</p> <p>Results</p> <p>The decoction showed cidal activity against <it>Giardia </it>and rotavirus whereas viability of none of the six bacterial strains tested was affected. It significantly reduced bacterial adherence to and invasion of HEp-2 cells. The extract also affected production of CT and binding of both LT and CT to GM1. However, it had no effect on ST.</p> <p>Conclusion</p> <p>The decoction of the unripe fruit pulp of <it>A. marmelos</it>, despite having limited antimicrobial activity, affected the bacterial colonization to gut epithelium and production and action of certain enterotoxins. These observations suggest the varied possible modes of action of <it>A. marmelos </it>in infectious forms of diarrhoea thereby validating its mention in the ancient Indian texts and continued use by local communities for the treatment of diarrhoeal diseases.</p

Hypoglycaemic activity of extracts from soft corals of Andaman and Nicobar coasts in rats

180-181The ethylacetate extract of soft corals collected from Andaman and Nicobar Coasts were screened for hypoglycaemic activity in fasting rats. Rats were divided into 5 groups. Group I received 0.5 ml of 5% gum acacia suspension (control). Group II received the extract of Cladiella australis (CAS), at a dose of 250 mg/kg. Group III received the extract of Sinularia new species (SNS), at a dose of 75 mg/kg. Group IV received the extract of Lamnalia new species (LNS), at a dose of 400 mg/kg and Group V received the extract of 250MF-CBR-13 at a dose of 250 mg/kg. All extracts were administered orally. Blood samples, collected before the administration of test extracts and also at 2, 4, 6, and 8 hr after treatment , were analysed for glucose content. The percentage blood glucose reduction from that or control was also calculated. A very promising hypoglycaemic activity was observed in rats with CAS at 8 hr (42.3%), with SNS at 4 hr (28.34%) and 6 hr (40.6%), with LNS at 6 hr (32.38%) and with MF-CBR-13 at 6 hr (20.25%)