Formulation and Evaluation of Pseudoephedrine Hydrochloride Loaded Alginate Microbeads

Multiple unit dosage forms such as microbeads have increased acceptance because of added even spreading of the drug in the gastrointestinal tract, unvarying drug absorption, abridged local irritation and removal of undesirable intestinal retaining of polymeric material, when compared to non-disintegrating single unit dosage form. The purpose of the presented research is to develop microbeads of pseudoephedrine hydrochloride utilizing sodium alginate as the hydrophilic carrier in combination with HPMC as drug release modifier to lessen the dosing frequency and thereby advance the patient compliance. The microbeads were formulated by varying concentrations of HPMC and calcium chloride. The optimum formulation was chosen based upon in vitro drug release studies and further evaluated. The compatibility of drug-polymer was studied using FTIR analysis. The prepared formulation underwent evaluation for various parameters like drug entrapment, microbeads size, swelling index, mucoadhesive property and stability. No significant drug-polymer interactions were observed in compatibility studies and the formulation was found to be stable on 45 days storage. The formulations exhibited an extended drug release pattern which was the ultimate aim of the study. The microbeads represented good yield, high drug entrapment, low microbeads size and appropriate swelling property. The in vitro wash-off test indicated that the sodium alginate microbeads represent decent mucoadhesive properties. Henceforth, the formulated HPMC coated sodium alginate beads can be utilized as a substitute and cost-effective carrier for the oral controlled delivery of pseudoephedrine hydrochloride. Keywords: microbeads, pseudoephedrine hydrochloride, sodium alginate, drug releas

Inhibition of Innate Immune Responses of Polymorphonuclear Leucocytes and Monocytes by Rhinacanthin‑C

Phagocytosis is a pivotal microbicidal function of innate immune cells by which phagocytes would engulf and eliminate invading pathogens. The functioning and efficacy of immune system is altered by many pathogens e.g. bacteria and fungi and the nonspecific kind of innate immunity is responsible for providing protection against these invading pathogens. The aim of this study is to assess the inhibitory effect of rhinacanthin‑C on phagocytic activities to obtain important insights into its ability to suppress phagocytes. Phagocytosis activity of innate immune cell was monitored using a flowcytometer and myeloperoxidase activity assay was conducted using a myeloperoxidase activity colorimetric assay. Rhinacanthin‑C at 100.0 and 6.25 μg/ml significantly showed strong inhibition of phagocytosis with percentage of 26.40% and 30.59% respectively, in comparison with the positive control (p< 0.001). A dose-dependent (50.0, 25.0, 12.5, 6.25 and 3.13 μg/ml) inhibition of MPO activity of rhinacanthin-C was observed and show high activity compared to control cells (p< 0.001). This finding indicated that rhinacanthin-C was able to suppress human phagocyte response and emphasizing their potency as immunomodulatory agents. Nevertheless, further investigations are needed to elucidate other immunomodulatory responses. Keywords: macrophage, monocyte, myeloperoxidase, phagocytosis, rhinacanthin-

Design of Some Benzimidazoles as Target for α-Glucosidase Inhibitors

Diabetes mellitus is rising globally touching more than 180 million people worldwide. This is prevailing mostly in type 2 diabetes and according to WHO report the incidence is likely to be more than doubled by 2030. α-Glucosidase inhibitors work by reducing the amount of glucose that the intestines absorb from food. In this work, forty-five benzimidazole analogues were studied using 3D QSAR, HQSAR, pharmacophore mapping and based on their results 60 compounds were designed. The results show that the best Comparative Molecular Field Analysis (CoMFA) model has q2 = 0.742 and r2 = 0.973, and the best Comparative Molecular Similarity Indices Analysis (CoMSIA) model has q2 = 0.679 and r2 = 0.918. For HQSAR the best model has q2 = 0.773 and r2 = 0.964. The r2 value for boostrap for CoMFA and CoMSIA are 0.98 and 0.97 respectively. Pharmacophore mapping revealed varied bioactive regions of ligand. Thus, these compounds could be used as lead for designing the synthesis of potent alpha-glucosidase inhibitors. Keywords: Acarbose, Alpha-glucosidase inhibition, Benzimidazoles, Molecular modelling, Post-prandial hyperglycemi

Synthesis and Biological Evaluation of Benzimidazoles as Target for α-Glucosidase Inhibitors

Diabetes mellitus is rising globally touching more than 180 million people worldwide. This is prevailing mostly in type 2 diabetes and according to WHO report the incidence is likely to be more than doubled by 2030. α-glucosidase inhibitors work by reducing the amount of glucose that the intestines absorb from food. In our previous work, forty-five benzimidazoles analogues were studied using 3D QSAR, HQSAR, and Pharmacophore mapping and based on their results 60 compounds were designed. Docking studies of those designed compounds showed that most of the compounds are bonding with important amino acids LEU 520, ARG 335 and ASP 69 through hydrogen bonds and steric interaction. In this work, synthesis of eleven compounds was done on the basis of molecular docking studies. Compounds containing hydroxyl and alkyl groups (compound no. 3, 9 and 10) were found to be five to eight folds more active with IC90 values in the range of 6.02 ± 1.10 to 33.25 ± 1.20 µg/ml, in comparison with the standard drug, Acarbose (IC90= 290.55 ± 0.081 µg/ml). Thus, these compounds after the toxicity studies could be of therapeutic use in treating diabetes. Keywords: Acarbose, Alpha-glucosidase inhibition, Benzimidazoles, Docking, Molecular modelling, Post-prandial hyperglycemi

IN VITRO ADME STUDIES OF TUG-891, A GPR-120 INHIBITOR USING SWISS ADME PREDICTOR

Predicting the absorption, distribution, metabolism and elimination (ADME) profile of drug candidates before their synthesis, in the early stage of drug discovery, could help in selecting candidates with the less critical ADME profile. In vivo ADME assessment is found to be costly, time consuming and involve the lives of animals, so the in vitro ADME analysis is better, cheaper and provides accurate results quickly. TUG-891 is a GPR-120 inhibitor under clinical trials. The aim of the present study is to predict the in vitro ADME studies of TUG-891, to know the expected outcome of the clinical trials and finding the correlation between the in vivo and in vitro results along with the improvisation in the structure of the TUG-891, so that the biological activity remains unaffected, but reduces the unwanted ADME effects. The 2D and 3D structures of TUG-891 were drawn on chemdraw 3D-Ultra version 8.0 by minimizing the energy using MM2 and MOPAC setting the minimum RMS gradient to 0.01. The structure was imported, the structure smiley was entered and the Swiss ADME drug design study was run. The bioavailability radar showed that the colored zone is the suitable physicochemical space for oral bioavailability where the following properties were taken into consideration as flexibility, lipophilicity, saturation, size, polarity and solubility. The pharmacokinetic properties were studied using the boiled egg model allows for intuitive evaluation of passive gastrointestinal absorption and brain penetration in function of the position of the molecules in the WLOGP-versus-TPSA referential. The white region is for high probability of passive absorption by the gastrointestinal tract and the yellow region that is yolk, is for high probability of brain penetration. Yolk and white areas are not mutually exclusive. Through the study conducted it could be concluded that the aqueous solubility of the compound should be increased along with the fraction of sp3 hybridized carbon atoms. The molecule should not be the inhibitor of metabolizing enzymes and so further modifications need to be done on the lead structure

FORMULATION AND IN-VITRO EVALUATION OF GASTRO RETENTIVE BILAYER FLOATING TABLET OF FAMOTIDINE HYDROCHLORIDE

The present study aims to formulate bilayered tablets of famotidine hydrochloride with a fast release layer using sodium starch glycolate, cross povidone and a sustaining floating layer using polymers like HPMC K100M and HPMC K15M by effervescent approach. The release characteristics were studied on the basis of gel forming polymer, methocel with different concentration of citric acid and sodium bicarbonate. The in vitro buoyancy and floatability were found to be optimum in combination of sodium bicarbonate, citric acid and methocel at concentration of 13 mg, 6 mg and 90 mg respectively. The drug release from floating tablets was found to be 93.87% for F1 with methocel K15M. The drug release was sustained for a period of 20-24 hours. When compared different grades of methocel (K100M and K15M), the methocel K15M (low viscosity grade) provided better-sustained release characteristics with excellent in vitro buoyancy. The IR study reveals that there is no any possible interaction between drug and excipients used for such formulation. The data from release studies were fitted in different models viz. zero order, first order and Korsemeyer’s equation. The result indicated the coupling of swelling and diffusion mechanism so called as Fickian diffusion of famotidine from floating tablets. Keywords: Bilayered tablets, Fast release layer, Floating layer, Polymers: HPMC, K100M, HPMC K15M, Methocel, Citric acid, Sodium bicarbonate, Famotidine hydrochloride

Design and development of gastro retentive drug delivery System of tramadol hydrochloride

The present investigation concerns the development of floating tablets of tramadol hydrochloride, which after oral administration are designed to prolong the gastric residence time; improves the drug bioavailability, reduces drug waste and diminish the side effects of drug. The D-optimal experimental design was employed to evaluate contribution of hydroxypropyl methyl cellulose (HPMC) K4M concentration, lactose concentration and kollidone SR concentration on drug release from floating tablets. Tablets were prepared using direct compression technique. Formulations were evaluated for in vitro buoyancy and drug release study using United States Pharmacopoeia (USP) 24 paddle type dissolution apparatus using 0.1 N HCl as dissolution medium. Multiple regression analysis was performed for factorial design batches to evaluate the response. All formulation had floating lag time below 2 min and constantly floated on dissolution medium for more than 24 h. It was found that optimized HPMC K4M (100 mg), kollidone SR (25 mg) and lactose (17.5 mg) have shown the release of 98.4 % in 22 h which was better as compare to marketed product (i.e. Tramazac-SR). Kinetic treatment to dissolution profiles revealed the diffusion mechanism so called as Fickian diffusion (Case I transport) which was mainly dependent on all the independent variables.Colegio de Farmacéuticos de la Provincia de Buenos Aire

SOLID AS SOLVENT: NOVEL SPECTROPHOTOMETRIC ANALYTICAL TECHNIQUE FOR QUANTITATIVE ESTIMATION OF TINIDAZOLE IN TABLETS USING SOLIDS (EUTECTIC LIQUID OF PHENOL AND LIGNOCAINE HYDROCHLORIDE) AS SOLUBILIZING AGENTS (MIXED SOLVENCY CONCEPT)

As per the mixed solvency concept, every substance present in this universe has got solubilizing power. The substance may be a gas, liquid or solid. The present research work is an attempt to demonstrate the solubilizing property of solids. Also, the present research work is one of the examples which prove that solids can also be employed for spectrophotometric analysis of poorly soluble drugs in place of organic solvents. Tinidazole has got poor solubility in distilled water, while, significantly high solubility in a eutectic liquid of two solids, namely, phenol and lignocaine hydrochloride. Phenol and lignocaine hydrochloride were employed in 4:1 ratio to give eutectic liquid (PL 41). This eutectic liquid was employed to act as solvent to extract out the drug, tinidazole, from the fine powder of its tablets for spectrophotometric estimation at 318 nm. Necessary dilutions were done using distilled water. The solubility of tinidazole in distilled water is 5.38 mg/ml at room temperature while the approximate solubility in PL 41 is more than 200 mg/ml. Proposed method is novel, accurate, rapid and free from toxicity of organic solvents and reproducible. Recovery studies and statistical data proved the accuracy, reproducibility and precision of the analytical method employed. Tablet excipients together with phenol and lignocaine hydrochloride did not interfere at 318 nm. Keywords - Spectrophotometric analysis, mixed-solvency concept, tinidazole, phenol – lignocaine hydrochloride eutectic liqui

Anxiolytic Potency of Cardamonin Mediated through Brain GABAergic System

Anxiety is an ailment causing personal, social and economic burden. Some drugs are available to provide symptomatic assistance for the treatment of anxiety and attempts are being made to find new therapeutic entities and subside associated adverse effects. Approaching natural sources, the current study aims to investigate the anxiolytic effects of cardamonin and its effect on the brain GABAergic system. The anxiolytic effects of various dose of cardamonin were investigated using the elevated plus maze apparatus and possible motor disabilities were evaluated trough open field test. Possible impact on GABAergic system was investigated using the ELISA. Fourteen days treatment with cardamonin (5.0 and 10.0 mg/kg, i.p.) in mice significantly (p < 0.0001) increased and the percentages of open arm entry and open arm time compared to respective vehicle control group. Cardamonin show no influence on gross locomotor movement in open field test. Treatment with cardamonin significantly (p < 0.0001) increased levels of GABA in brain of treated mice compared to control mice. This study provided evidence on the anxiolytic potency of the cardamonin and revealed its action mechanism of regulating the GABA level in mouse brain

Formulation and evaluation of aceclofenac mouth-dissolving tablet

Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities similar to indomethacin and diclofenac, and due to its preferential Cox-2 blockade, it has a better safety than conventional Non steroidal anti-inflammatory drug (NSAIDs) with respect to adverse effect on gastrointestinal and cardiovascular systems. Aceclofenac is superior from other NSAIDs as it has selectivity for Cox-2, a beneficial Cox inhibitor is well tolerated, has better Gastrointestinal (GI) tolerability and improved cardiovascular safety when compared with other selective Cox-2 inhibitor. To provide the patient with the most convenient mode of administration, there is need to develop a fast-disintegrating dosage form, particularly one that disintegrates and dissolves/disperses in saliva and can be administered without water, anywhere, any time. Such tablets are also called as “melt in mouth tablet.” Direct compression, freeze drying, sublimation, spray drying, tablet molding, disintegrant addition, and use of sugar-based excipients are technologies available for mouth-dissolving tablet. Mouth-dissolving tablets of aceclofenac were prepared with two different techniques, wet granulation and direct compression, in which different formulations were prepared with varying concentration of excipients. These tablets were evaluated for their friability, hardness, wetting time, and disintegration time; the drug release profile was studied in buffer Phosphate buffered Saline (PBS) pH 7.4. Direct compression batch C3 gave far better dissolution than the wet granulation Batch F2, which released only 75.37% drug, and C3, which released 89.69% drug in 90 minutes