A B S T R A C T Objective:To design solid self-microemulsifying drug delivery system (S-SMEDDS) of entacapone and evaluate for its anti-Parkinson's potentials. Methods: Solubility studies were performed in various vehicles i.e., oils, surfactants and co-surfactants and pseudo-ternary phase diagrams were plotted to understand the microemulsion formation region. Liquid self-microemulsifying drug delivery systems (SMEDDS) were developed using gingelly and rice bran oil as lipid vehicles, Tween 80 and Span 20 as surfactants and glycerin, propylene glycol as co-surfactants. They were characterized by Fourier transform infrared spectroscopy, pH, viscosity, zeta potential, polydispersibility index and droplet size analysis and evaluated for drug content, in-vitro release, in-vitro diffusion and ex-vivo permeation. Optimized liquid SMEDDS were converted into S-SMEDDS by adsorption and melt granulation procedures. Characterization by differential scanning calorimetry, SEM, micrometrics, reconstitution property, moisture content and evaluation by drug content, drug release kinetics and shelf-life were performed for S-SMEDDS. Parkinsonism was induced and pharmacodynamic potentials of S-SMEDDS were evaluated. Results: S-SMEDDS formulation AG8 had shown the highest drug release of 90.92% within 60 min. Pharmacodynamic studies also proved the efficiency of entacapone S-SMEDDS against Parkinsonism. Conclusions: Entacapone S-SMEDDS is an effective drug delivery system that offers more predictable and extensive drug release with enhanced shelf-life in the treatment of acute Parkinsonism.

Objective:The main objective of this work was to develop a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Canagliflozin and Metformin. Methods: Deuterated compounds of respective drugs were used an internal standard. Sample extraction was carried out using a simple Protein Precipitation (PP) technique. A C 18 column with an isocratic mobile phase composed of 5mM ammonium acetate with 0.01% formic acid and methanol were used for chromatographic separation. Results: The method was validated in the linearity range of 10.00-6028.00 ng/mL for Canagliflozin and 10.00-3027.00 ng/mL for Metformin. The precision and accuracy results over five concentration levels in five different batches were well within the acceptance limits. A variety of stability tests were executed in plasma and in neat samples are comply with the FDA guidelines. Conclusion: The proposed assay method is simple, rapid and sensitive for the simultaneous determination of Canagliflozin and Metformin in human plasma. This method was successfully used to quantitate the in vivo plasma concentrations obtained from a pharmacokinetic study.

Oxaprozin is a popular non-steroidal anti-inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one-pot reaction using N,N-carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000-90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT-IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first-order kinetics with 55.2 min of half-life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti-inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.

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