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 hyperglycemia
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.
T he purpose of this research was to mask the intensely bitter taste of metoclopramide hydrochloride and to formulate a rapid-disintegrating tablet of the taste-masked drug. Taste masking was done by complexing the drug with ion exchange resin, Indion 204 and Indion 214, in different ratios. The complex loading process was optimized for the concentration of resin, swelling time, stirring time, pH, and temperature for maximum drug loading. Drug-resin complexes (DRC) were tested for flow properties, drug content, in-vitro release in simulated salivary fluid, and in simulated gastric fluid (SGF), taste evaluation by the panel method. Taste evaluation of DRC revealed considerable taste masking with the degree of bitterness below threshold value (40 µg/ml) in 0 to 5 min. Complex of both Indion 204 and Indion 214 masked the taste, but on the basis of the comparative study, resin 214 was selected for taste masking property. Disintegrant croscarmellose (5% wt/wt) gave the minimum disintegration time in comparison to crosspovidone and sodium starch glycolate. The batch of tablet containing Pearlitol SD and Avicel (PH102) in the ratio 60:40 and 5% (wt/wt) Croscarmellose showed faster disintegration i.e. 32 s, as compare to marketed tablet. It also revealed rapid drug release (t 80 , 6 min) in SGF compared with marketed formulation (t 80 , 9 min).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.