Development and Characterization of Pentaerythritol-EudragitRS100 Co-processed Excipients as Solid Dispersion Carriers for Enhanced Aqueous Solubility, In Vitro Dissolution, and Ex Vivo Permeation of Atorvastatin.

Atorvastatin (ATV), a lipid-lowering agent, has low oral bioavailability due to its poor water solubility, permeability, and low dissolution rate. Therefore, pentaerythritol-EudragitRS100 co-processed excipients (PECE) were synthesized, and their feasibility as solid dispersion carriers (ATV-PECE-SD) for improving the solubility, permeability, and dissolution rate of ATV was explored. Solid dispersions were assessed in terms of particle size and zeta potential, and solubility, in vitro dissolution, and ex vivo permeation studies were studied. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) were used as characterization tools. ATV-PECE-SD3 (1:4) formulations exhibited a small particle size with high stability. Physicochemical evaluation evidenced the formation of solid dispersion due to the involvement of weak electrostatic interaction between the polar functional groups of ATV and PECE carriers. ATV-PECE-SD3 (1:4) significantly enhanced the water solubility by ∼43-fold compared to pure ATV. In vitro dissolution studies showed that optimized formulation enhanced the dissolution rate of ATV compared to pure ATV. Ex vivo permeation results revealed that ATV-PECE-SD3 (1:4) enhanced the permeation rate of ATV compared to pure ATV. The optimized formulations significantly improved the dissolution rate of ATV in the fed state due to the food effect and micelle formation mechanism compared to the fasted state. The study concludes that co-processed excipients could be used as promising solid dispersion carriers to enhance the aqueous solubility, permeability, and dissolution rate of ATV.

Reversed-phase high-performance liquid chromatographic method development and validation for allyl isothiocyanate estimation in phytosomes of Brassica nigra extract.

A simple, specific, accurate, precise, and robust reverse-phase high-performance liquid chromatographic method has been developed and validated for the estimation of allyl isothiocyanate (AITC) in phytosomes of black mustard extract (Brassica nigra). The method was validated with respect to specificity, linearity, accuracy, precision, and robustness. The linearity was achieved over a range of 10-18 µg/mL and regression coefficient was obtained 0.9961. Accuracy of chromatographic method was evaluated by standard addition method; percentage recovery attained was 97.07 ± 0.008-103.66 ± 0.013. Relative standard deviation for intraday and interday precision was 0.02% and 0.22%, respectively. The limit of detection and limit of quantification of the AITC were found to be 0.0043 µg/mL and 0.01324 µg/mL, respectively. This result shows that the method was well validated. In the present study, the AITC content was found 0.0009% ± 0.014% in black mustard. This study reveals that the proposed high-performance thin-layer chromatography method is accurate, fast, and cost-effective for the routine estimation of AITC in the phytosome formulation.

Aminocarbonyl arylvinylbenzamides as gastric sparing anti-inflammatory agents.

Some (E/Z)-aminocarbonyl arylvinylbenzamides (B1-B15) were synthesized, evaluated for anti-inflammatory activity and ulcerogenic tendency, and their effect on gastro-intestinal motility in the rats was studied. These benzamides comprising of aliphatic unsaturated region situated between two amide linkages were synthesized by nucleophilic ring opening of appropriate azlactones (AZ1-AZ4) by suitable amines. The characterization of newly synthesized benzamides was performed by IR, (1)H- and (13)C-NMR, mass and elemental analysis. Amongst the tested compounds, benzamide B1, B2, B4, B5, and B13 were able to produce comparable or superior anti-inflammatory activity at 10 and 20 mg/kg p.o. dose with respect to standard diclofenac in carrageenan induced rat paw edema model with lessened propensity to cause gastro-intestinal hypermotility and were found to have nil tendencies to generate gastric ulcers.

Bioactivity guided isolation and characterization of the phytoconstituents from the Tridax procumbens

Tridax procumbens L., Asteraceae, has been extensively used in Ayurvedic system of medicine for various ailments. Previous studies on the extracts of T. procumbens revealed remarkable immunomodulatory activity of TPEIF (T. procumbens ethanol insoluble fraction) extract. The dried methanol extract of T. procumbens was dissolved in distilled water, and then fractioned by re-extracting with chloroform, ethyl acetate and n-butanol subsequently. Immunomodulatory activities of these fractions were determined in vivo. The amounts of total phenolic compounds were also determined. Ethyl acetate and n-butanol fractions showed the significant immunomodulary activity. However, the ethyl acetate fraction exhibited the highest total phenolic content. Therefore, ethyl acetate fraction was subjected to further separation by chromatographic methods. Two phytochemicals SA-3 and SA-4 were obtained by repeated purification in sufficient amount to screen them for the immunomodulatory activity by the in vivo models i.e. neutrophil adhesion and delayed type hypersensitivity. In addition, the n-butanol fraction was subjected to silica gel column chromatography (CC); SA-6 was isolated from it. Mice were treated with two doses of SA-3, SA-4 and SA-6 (2 and 4 mg/kg) for fifteen days. Immune responses to T-dependent antigen SRBCs were observed using parameters like DTH and Neutrophil adhesion. Overall, SA-4 and SA-6 showed dose relative immunostimulatory effect on in vivo immune functions in mice. From these results, it can be suggested that these compounds may be used as potential immunostimulators. The structures of isolated phytochemicals were determined by UV, IR, NMR, and MS spectroscopic methods.