Enhancement of dissolution rate and intestinal stability of candesartan cilexitil.

The objective of this work was to improve the dissolution rate of candesartan cilexitil, a poorly water soluble prodrug and to reduce its premature degradation in the intestinal lumen. Binary and ternary solid dispersions (SD) of the drug with Pluronic F68, Polyvinyl pyrrolidone (PVP), Hydroxypropyl Methylcellulose (HPMC) and Tween 80 were prepared using the solvent evaporation method. The dissolution rate of the drug was monitored and the prepared SD systems were characterized using thermal analysis and Fourier transform infrared (FTIR) spectroscopy. The stability of candesartan in extracted rabbit intestinal fluids was monitored. This was conducted in absence and presence of tested excipients. SD of the drug with PVP resulted in significant enhancement in the dissolution rate of drug even at the lowest drug to polymer weight ratio. Similarly, SD with HPMC showed enhanced dissolution rate. SD with Pluronic F68 showed promising dissolution enhancement but this was recorded at higher polymer concentrations. Formulation of ternary SD of the drug and PVP with either Pluronic or Tween 80 resulted in rapid drug dissolution. The enhanced dissolution was mainly due to amorphousization of the drug with possible contribution to the micelle formation as reflected from thermal analysis. Incubation of pure candesartan in intestinal fluid resulted in rapid degradation of the drug. This degradation was not affected by 0.1% Pluronic. In presence of Tween 80 the rate of drug degradation was reduced significantly with the efficacy of Tween 80 depending on its concentration. The study developed a system for enhanced dissolution rate of candesartan with better stability in the intestinal lumen.

Optimization studies on production of a salt-tolerant protease from Pseudomonas aeruginosa strain BC1 and its application on tannery saline wastewater treatment

Treatment and safe disposal of tannery saline wastewater, a primary effluent stream that is generated by soaking salt-laden hides and skin is one of the major problems faced by the leather manufacturing industries. Conventional treatment methods like solar evaporation ponds and land composting are not eco-friendly as they deteriorate the ground water quality. Though, this waste stream is comprised of high concentration of dissolved proteins the presence of high salinity (1-6 percent NaCl by wt) makes it non-biodegradable. Enzymatic treatment is one of the positive alternatives for management of such kind of waste streams. A novel salt-tolerant alkaline protease obtained from P.aeruginosa (isolated from tannery saline wastewater) was used for enzymatic degradation studies. The effect of various physical factors including pH, temperature, incubation time, protein source and salinity on the activity of identified protease were investigated. Kinetic parameters (Km , Vmax) were calculated for the identified alkaline protease at varying substrate concentrations. Tannery saline wastewater treated with identified salt tolerant protease showed 75 percent protein removal at 6 h duration and 2 percent (v/v) protease addition was found to be the optimum dosage value.

Enzymatic degradation of marine polysaccharide YCP and analysis of YCP-derived fragments / 中国药科大学学报

Aim: To explore the relationship between structure and immunological activity of marine polysaccha-ride YCP,the physicochemical property and immunological activity of the YCP-derived fragment were studied.Methods: YCP was hydrolyzed by α-amylase from human saliva.The hydrolysate was purified to obtain an polysaccharide fragment by gel filtration chromatography.The physicochemical properties of this YCP-derived fragment was characterized by HPLC,FT-IR and TLC.In addition,changes of phagocytic activity,production of reactive nitrogen and macrophage binding were investigated.Results: The relative molecular weight of YCP-de-rived fragment was approximately 6.6 × 10~3.The monosaccharide composition and FT-IR of the YCP-derived frag-ment were identical to YCP.No significant effect of the YCP-derived fragment on NO production and murine mac-rophage phagocyte were observed.And this fragment was not able to compete the binding between YCP and mac-rophages.Conclusion: The remarkable decrease of immunological activity of YCP-derived fragments degraded byα-amylase of human saliva suggests that the complete structure and high molecule weight of YCP are essential for its immuno-modulatory activity.