DEVELOPMENT AND IN VIVO EVALUATION OF MUCOADHESIVE MICROSPHERES USING PIRENZEPINE

Objective: The current investigation objective was to fabricate gastroretentive mucoadhesive microspheres of pirenzepine and to investigate the pharmacokinetic parameters of optimized formulation in comparison with a marketed product.Methods: Pirenzepine mucoadhesive microspheres prepared using ionotropic gelation technique. Evaluation parameters and characterization such as Fourier transform infrared (FTIR) and scanning electron microscopy were performed. In vivo bioavailability studies were conducted in rabbits. The technique used was found to be handling easy, inexpensive, and reproducible process.Results: Among the total 14 formulations, M13 formulation was optimized and showed free flowing with good packability. FTIR studies investigated incompatibility were not observed between drug and excipients. The optimized formulation (M13) showed best cumulative percentage drug release of pirenzepine up to 99.07±0.17% within 12 h whereas marketed product displayed the drug release of 95.23±0.21% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer–Peppas model (R2=0.951 and 0.994), respectively. Optimized formulation (M13) was stable at 40°C±2°C/75% RH±5% RH for 6 months. Form in vivo studies, the optimized formulation bioavailability was much higher than the marketed product.Conclusion: Microspheres would be a promising drug delivery system could play a potentially significant role in pharmaceutical drug delivery in a controlled manner for an extended period of time for effective management of gastritis

Development and in vivo evaluation of mucoadhesive tablets of Lafutidine

The aim of the present work was in vitro and in vivo evaluation of mucoadhesive tablets of lafutidine to prolong the gastric residence time after oral administration. Formulations were prepared using 33 full factorial designs to explore the effects of Gum Kondagogu, Gum Olibanum and Guar Gum (as independent variables) on mucoadhesive strength, drug release and Ex vivo residence time (as dependent variables) was studied and published in the earlier research paper.In this investigation the formulated mucoadhesive tablets which was optimized through in vitro studies is selected and performed the in vivo studies on Human volunteers. The drug-polymer interaction was also studied by conducting FTIR and DSC tests. The in vitro release kinetics studies reveal that all formulations fits well with Zero order, followed by Korsmeyer-Peppas, Higuchi and the mechanism of drug release is erosion. After analysis of different evaluation parameters and drug release kinetics, formulation code F22 was selected as a promising formulation for delivery of lafutidine as a mucoadhesive Gastroretentive tablet with best mucoadhesive strength and 99.54% drug release at 12th hour. Radiological evidences suggest that, a formulated tablet was well adhered for >10 h in human stomach. The bioavailability studies of F22 containing lafutidine was carried out which exhibited increased pharmacokinetic parameters of Cmax (268±1.26), Tmax (1.30±1.23 h) and AUC0-t (1048±16.42) as compared to marketed formulations which indicates improved bioavailability of formulations.

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF SOME NOVEL 3,4-DISUBSTITUTED PYRAZOLE DERIVATIVES

Objective: The objective of the current work was to synthesize a series of 3,4-substituted pyrazoles from the cyclization of substituted aryl ethanone and hydrazine hydrate in a two-step process and screen the derivatives for their antimicrobial activity. Methods: The title compounds were derived from the condensation of ethanone intermediate with N, N-Dimethyl formamide-dimethyl acetal and hydrazine hydrate. Ethanone intermediate synthesized from substituted methyl phenylacetate in the presence of potassium t-butoxide with 6-methyl pyridine-2-carboxylic acid methyl ester. Results: The final products were characterized by detailed spectral analysis using Mass, Nuclear Magnetic Resonance, and Infra Red spectroscopy. All the compounds (4a-4j) showed significant antibacterial properties on both Gram-positive and Gram-negative bacteria. Interestingly, the selected microbes were found to be highly sensitive for compound 4a, 4c, 4d, 4h, and 4i. The molecules are also antifungal in nature, and they have a significant inhibitory effect on the growth of Candida albicans and Aspergillus niger. Conclusion: The results suggest that the developed derivatives bearing the pyrazole nucleus could be the lead structures for the development of antimicrobial agents for fatal infections

Development and in vivo evaluation of mucoadhesive tablets of Lafutidine

The aim of the present work was in vitro and in vivo evaluation of mucoadhesive tablets of lafutidine to prolong the gastric residence time after oral administration. Formulations were prepared using 33 full factorial designs to explore the effects of Gum Kondagogu, Gum Olibanum and Guar Gum (as independent variables) on mucoadhesive strength, drug release and Ex vivo residence time (as dependent variables) was studied and published in the earlier research paper.In this investigation the formulated mucoadhesive tablets which was optimized through in vitro studies is selected and performed the in vivo studies on Human volunteers. The drug-polymer interaction was also studied by conducting FTIR and DSC tests. The in vitro release kinetics studies reveal that all formulations fits well with Zero order, followed by Korsmeyer-Peppas, Higuchi and the mechanism of drug release is erosion. After analysis of different evaluation parameters and drug release kinetics, formulation code F22 was selected as a promising formulation for delivery of lafutidine as a mucoadhesive Gastroretentive tablet with best mucoadhesive strength and 99.54% drug release at 12th hour. Radiological evidences suggest that, a formulated tablet was well adhered for >10 h in human stomach. The bioavailability studies of F22 containing lafutidine was carried out which exhibited increased pharmacokinetic parameters of Cmax (268±1.26), Tmax (1.30±1.23 h) and AUC0-t (1048±16.42) as compared to marketed formulations which indicates improved bioavailability of formulations.

Preparation, optimization and in vivo evaluation of Eletriptan HBR fast dissolving oral films

The present investigation was aimed with the objective of developing fast dissolving oral films of Eletriptan HBr in order to attain quick onset of action for the better management of migraine attack. Twenty five formulations were prepared by solvent casting method using different polymer types, plasticizer types, surfactant concentrations and different ratio of hydroxypropyl methyl cellulose and maltodextrin. The prepared films were evaluated for folding endurance, thickness, drug content, in vitro/in vivo disintegration time, drug release and tensile test. The optimized formulation F17 containing HPMC 15cp and maltodextrin showed minimum in vitro disintegration time 11 seconds, highest dissolution rate i.e. 98.5% of drug within 10 min. The optimized film was further evaluated for bioavailability compared with a marketed product (Relpax-20mg). The pharmacokinetic results revealed that the fast dissolving oral films has higher peak blood concentration (Cmax, 0.455±0.1µg/ml) within shorter time (Tmax, 0.5 hours), indicating rapid absorption and faster onset of action with acceptable bioavailability value. Therefore, the oral fast dissolving film is considered to be potentially useful for the treatment of migraine disease where quick onset of action is desired, also improved patient compliance

Preparation and in vivo evaluation of SMEDDS containing Nevirapine for bioavailability improvement

Nevirapine has been formulated in lipid-based system, a Self Emulsifying Drug Delivery System (SEDDS) to target the drug to lymphoid organs where HIV-1 virus resides in large population. Nevirapine SEDDS were formulated for enhancement of solubility, dissolution rate and oral bioavailability of model drug Nevirapine. Fourteen formulations were prepared using different oils, surfactants and co-surfactants. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. Further, the resultant formulations were investigated for clarity, phase separation, drug content, % transmittance, globule size, freeze-thaw stability and in vitro dissolution studies. On the basis of dissolution profile and other above mentioned studies, F4 was found to be the best formulation of Nevirapine SEDDS which contains Capryol 90 (Oil), Tween 80 and PEG 600 as surfactant co-surfactant respectively. In vivo studies revealed that the oral bioavailability of Nevirapine from SEDDS was 2-fold higher compared to that of pure Nevirapine suspension in rats, suggesting a significant increase in oral bioavailability of Nevirapine from SEDDS formulation. The higher bioavailability might be due to the enhanced solubility of Nevirapine by SEDDS formulation

DESIGN AND IN VIVO EVALUATION OF METOPROLOL TARTRATE BILAYER FLOATING TABLETS IN HEALTHY HUMAN VOLUNTEERS

The aim of the present investigation was to prepare bilayer floating tablets of metoprolol tartrate using the combination of superdisintigrants, HPMC K grade polymers and natural polymers like xanthan gum and guar gum by direct compression method. Bilayer floating tablets were prepared using optimized immediate release layer and floating layer as sustained release layer. The physico-chemical characteristics of the prepared tablets were evaluated and found to be satisfactory. All the prepared batches showed in vitro buoyancy. It was observed that the tablets remained buoyant for more than 12 h.  Formulation F7 was selected as best formulation based on the in vitro characteristics and used in vivo radiographic studies by adding barium sulphate. These studies revealed that the tablets remained in the stomach for 210±5.4 min (n=3) in fasting human volunteers. Based on the in vivo performance in healthy subjects, the developed bilayer floating tablets showed superior bioavailability than the marketed tablets, the drug release was up to 12 h in controlled manner. The systemic availability of the best formulation was high after administration to obtain immediate action due to the immediate release layer, from sustained release layer the drug was released in controlled manner. It can be concluded that the best formulation F7 by choosing biphasic drug release pattern in a single dosage form could improve patient compliance and ensure better disease management

Preparation and in vivo evaluation of SMEDDS containing Nevirapine for bioavailability improvement

Nevirapine has been formulated in lipid-based system, a Self Emulsifying Drug Delivery System (SEDDS) to target the drug to lymphoid organs where HIV-1 virus resides in large population. Nevirapine SEDDS were formulated for enhancement of solubility, dissolution rate and oral bioavailability of model drug Nevirapine. Fourteen formulations were prepared using different oils, surfactants and co-surfactants. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. Further, the resultant formulations were investigated for clarity, phase separation, drug content, % transmittance, globule size, freeze-thaw stability and in vitro dissolution studies. On the basis of dissolution profile and other above mentioned studies, F4 was found to be the best formulation of Nevirapine SEDDS which contains Capryol 90 (Oil), Tween 80 and PEG 600 as surfactant co-surfactant respectively. In vivo studies revealed that the oral bioavailability of Nevirapine from SEDDS was 2-fold higher compared to that of pure Nevirapine suspension in rats, suggesting a significant increase in oral bioavailability of Nevirapine from SEDDS formulation. The higher bioavailability might be due to the enhanced solubility of Nevirapine by SEDDS formulation

DESIGN AND IN VIVO EVALUATION OF METOPROLOL TARTRATE BILAYER FLOATING TABLETS IN HEALTHY HUMAN VOLUNTEERS

The aim of the present investigation was to prepare bilayer floating tablets of metoprolol tartrate using the combination of superdisintigrants, HPMC K grade polymers and natural polymers like xanthan gum and guar gum by direct compression method. Bilayer floating tablets were prepared using optimized immediate release layer and floating layer as sustained release layer. The physico-chemical characteristics of the prepared tablets were evaluated and found to be satisfactory. All the prepared batches showed in vitro buoyancy. It was observed that the tablets remained buoyant for more than 12 h.  Formulation F7 was selected as best formulation based on the in vitro characteristics and used in vivo radiographic studies by adding barium sulphate. These studies revealed that the tablets remained in the stomach for 210±5.4 min (n=3) in fasting human volunteers. Based on the in vivo performance in healthy subjects, the developed bilayer floating tablets showed superior bioavailability than the marketed tablets, the drug release was up to 12 h in controlled manner. The systemic availability of the best formulation was high after administration to obtain immediate action due to the immediate release layer, from sustained release layer the drug was released in controlled manner. It can be concluded that the best formulation F7 by choosing biphasic drug release pattern in a single dosage form could improve patient compliance and ensure better disease management