Formulation and pharmacokinetics of ketorolac tromethamine fast dissolving tablets.

OBJECTIVE: The current study is intended to develop the fast dissolving tablets of Ketorolac tromethamine using different superdisintegrants to improve the dissolution rate and absorption rate to produce the bioavailability enhancement and rapid onset of action. METHODS: In this, Ketorolac tromethamine fast dissolving tablets were prepared using different superdisintegrants and evaluated for different physical parameters, in vitro dissolution studies and in vivo pharmacokinetics to demonstrate the bioavailability enhancement. RESULTS & DISCUSSIONS: From the in vitro drug release studies, in case of optimized formulation, the cumulative percent drug release in 15 min (Q15) was found to be 94.34±1.68 where as the conventional tablets showed 28.78±0.82 in 15 min. The initial dissolution rate and dissolution efficiency of optimized formulation was 6.29%/min and 53.43 but it was 1.92%/min and 14.03 in conventional tablets. From the in vivo pharmacokinetic evaluation, the optimized formulation showed peak plasma concentration (Cmax) as 1 248.39 ng/ml at 1 h Tmax, but they were found to be 988.22 ng/ml at 2 h Tmax, in case of conventional tablets. The area under the curve for the optimized and conventional tablets was 3 890.68 and 3 173.07 ng-h/ml. CONCLUSIONS: Hence the development of fast dissolving tablets using superdisintegrants was a good approach to improve the dissolution rate and absorption rate of Ketorolac tromethamine.

Pharmacokinetics and tissue distribution of piperine lipid nanospheres.

The purpose of this study was to estimate the pharmacokinetic parameters and tissue distribution of positively charged stearylamine (LN-P-SA) and pegylated lipid nanospheres (LN-P-PEG) of piperine in BALB/c mice. Lipid nanospheres of piperine (LN-P), LN-P-PEG and LN-P-SA were prepared by homogenization followed by ultrasonication. The pharmacokinetics and tissue distribution of different lipid nanosphere formulations (piperine, LN-P, LN-P-PEG and LN-P-SA) were studied in male BALB/c mice. The pharmacokinetic parameters of LN-P-PEG and LN-P-SA were: AUC(0-24): 372.1 +/- 71.6 and 162.2 +/- 36.4 microg h(-1) ml(-1), clearance 13 +/- 2.5 and 32 +/- 7.5 ml h(-1), Cmax: 24.7 +/- 1.5 and 22.3 +/- 1.0 microg ml(-1), Vd: 0.45 +/- 0.02 and 0.66 +/- 0.06 l Kg(-1)). Pharmacokinetics of piperine in lipid nanospheres showed a biexponential decline with significantly high AUC, a lower rate of clearance and a smaller volume of distribution than piperine.

Formulation and evaluation of oil-in-water emulsions of piperine in visceral leishmaniasis.

Present studies are aimed to find out the utility of oil-in-water emulsions also known as lipid nanospheres (LN) or fat emulsions for delivering piperine for the treatment of visceral leishmaniasis. Lipid nanosphere formulations of piperine were prepared using soybean oil, egg lecithin, cholesterol, stearylamine and phosphatidylethanolamine distearylmethoxypolyethyleneglycol (DSPE-PEG) by homogenization followed by ultrasonication of oil and aqueous phases. Antileishmanial activity of all the formulations was assessed in BALB/c mice infected with Leishmania donovani AG83 for 60 days. A single dose (5 mg/kg) of piperine, or lipid nanospheres of piperine (LN-P), or lipid nanosphere of piperine with stearylamine (LN-P-SA) or pegylated lipid nanospheres of piperine (LN-P-PEG) was injected intravenously. Mice were sacrificed after 15 days of treatment with piperine or formulations and Leishman Donovan Unit (LDU) is counted. Toxicity of formulations and pure piperine was assessed in normal mice. The size distribution of formulations ranged from 200 to 885 nm. Piperine reduced the parasite burden in liver and spleen by 38% and 31% after 15 days post infection respectively. LN-P reduced the parasite burden in liver and spleen by 63% and 52% after 15 days post infection, respectively. LN-P-PEG reduced the parasite burden in liver and spleen by 78% and 75% after 15 days post infection, respectively. LN-P-SA reduced the parasite burden in liver and spleen by 90% and 85% after 15 days post infection, respectively. LN-P, LN-P-PEG, LN-P-SA treated mice did not show any significant changes in the serum levels of SGOT, ALP, creatinine and urea compared to normal mice. Stable and sterile formulations of lipid nanospheres of piperine were developed. A single dose of 5 mg/kg of lipid nanospheres of piperine could significantly reduce the liver and splenic parasite burden.