SOLID DISPERSION TECHNIQUE TO ENHANCE THE SOLUBILITY AND DISSOLUTION RATE OF ARIPIPRAZOLE BY FUSION METHOD

Objective: The objective of the present study was to enhance the solubility and dissolution rate of Aripiprazole (APZ), a water insoluble drug, by a solid dispersion technique.Methods: Solid dispersions (SD) of APZ were prepared by fusion method using water-soluble carriers like, polyethylene glycol 4000 (PEG 4000), Croscarmellose sodium (CCS) and Crospovidone (CP) and were characterized by in-vitro dissolution, Fourier transform infrared (FTIR) spectroscopy and Differential scanning calorimetry (DSC) studies.Results: PEG 4000 physical mixtures containing APZ, showed enhanced dissolution rate as compared with pure drug. Binary solid dispersions showed an improvement in the dissolution rate when compared to the physical mixtures (PM) and pure drug. From ternary solid dispersions with CCS, formulation code SD9 showed 88.2% and with CP, formulation code SD15 showed 70.9%, whereas pure drug showed 18.8 % drug release at the end of 60 min. Based on the in-vitro dissolution studies of solid dispersions, the SD9 was selected to prepare tablets. From the dissolution studies of tablets, the formulation 4F3 showed rapid dissolution than other formulations and pure drug. FTIR, DSC studies suggesting that there was no physical and chemical interaction in between APZ and carriers.Conclusion: Hence, it can be concluded that ternary solid dispersions in association with super disintegrants were more effective to increase the dissolution rate of low soluble drug than solid binary dispersions, physical mixtures, and pure drug.Â

Spatial patterns in the diet of Gyps vultures in India and their implications for conservation

Dietary analyses are particularly useful for developing conservation programmes for species threatened by resource depletion, poisoning and environmental pollution. Gyps vultures in South Asia represent one such case, having undergone a population collapse caused by feeding on carcasses of cattle treated with the non-steroidal anti-inflammatory drug diclofenac. Following a ban on the veterinary use of diclofenac, populations of vultures remain low and mostly concentrated near protected areas. Understanding the role of protected areas in the recovery of these critically endangered species requires analyses of spatial variation in their diet. We used faecal metabarcoding to investigate the spatial variation in the diet of Gyps vultures across four landscapes from sites located inside and outside protected areas. We collected faecal 642 samples, of which 419 yielded adequate molecular data to identify the vulture species and 30 molecular operational taxonomic units corresponding to at least 28 diet species. The diet was dominated by large ungulates and varied across landscapes, protection status and vulture species, with the observed variation largely explained by differential intake of wild and domestic species. Domestic livestock was present in >95% of the samples from Central, West and North India, but 77% of the samples had only wild species in South India. This variation was explained by livestock density within 100 km radius of the sampling site. Our results imply that protected areas may not offer a respite from possibility of diclofenac-poisoning across most parts of the country and efforts should continue unabated to remove nephrotoxic drugs from veterinary use

Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

The direct CH-alkylation of indoles using carboxylic acids is presented for the first time. The catalytic system based on the combination of Co(acac)3 and 1,1,1-tris(diphenylphosphinomethyl)-ethane (Triphos, L1), in the presence of Al(OTf)3 as co-catalyst, is able to perform the reductive alkylation of 2-methyl-1H-indole with a wide range of carboxylic acids. The utility of the protocol was further demonstrated through the C3 alkylation of several substituted indole derivatives using acetic, phenylacetic or diphenylacetic acids. In addition, a careful selection of the reaction conditions allowed to perform the selective C3 alkenylation of some indole derivatives. Moreover, the alkenylation of C2 position of 3-methyl-1H-indole was also possible. Control experiments indicate that the aldehyde, in situ formed from the carboxylic acid hydrogenation, plays a central role in the overall process. This new protocol enables the direct functionalization of indoles with readily available and stable carboxylic acids using a non-precious metal based catalyst and hydrogen as reductant