Methotrexate

The objective of this study was to prepare the self-emulsifying drug delivery system of methotrexate for oral use. Preparation composed of soybean oil as oil phase, Span 80 as surfactants, isopropyl alcohol as co-surfactant, 0.1 N NaOH as the aqueous phase. Methotrexate is given orally in treatment of cancer and rheumatoid arthritis. The Anti-neoplastic drug MTX is having less aqueous solubility (50-60 %) and bioavailability of 60-70 %. Hence the present study is aimed to formulate and evaluate solid self-nano emulsifying drug delivery system with the aim of increasing the solubility and bioavailability which will decrease the dosing frequency in turn increase patient compliance. Liquid SNEDDS was prepared by adding drug to oil, surfactant and co-surfactant and heated up to at 60 ºC under continuous stirring until a clear solution is formed. All the formulations were optimized to get the best solubility results for MTX. Solid SNEDDS was prepared by mixing liquid SNEDDS with MCC in 1:1 proportion. The formulations were evaluated for angle of repose, bulk density, zeta potential, IR spectroscopy, in vitro dissolution, average particle size, size distribution and stability studies. The average particle size of the liquid SNEDDS was 60.4 nm and solid SNEDDS was 60.4nm. The surface charge was confirmed by the measurement of the zeta potential for the liquid SNEDDS and it was found to be -22.4 mV and that of the solid SNEDDS was -22.4 mV. The PDI value remained approximately around 0.565 indicated that all the nano particles were uniformly dispersed in the emulsion.

Two simple, precise and economical UV methods have been developed for estimation of Methotrexate in bulk formulation. Method A involves measurement of UV absorbance in Zeroorder derivative at 303nm. Method B deals with area under curve measurement (AUC method), which involves the calculation of integrated value of absorbance with respect to wavelength between 300-306nm.  The drug follows Beer-Lambert’s law in the concentration range of 3-15μg/ml in both the methods. Results of analysis were validated statistically and were found to be satisfactory. Thus proposed methods can be successfully applied for estimation of Methotrexatein routine analytical work.

Methotrexate is considered as the standard drug treatment for Rheumatoid arthritis. The purpose of this study is to find out the incidence of Adverse Drug Reactions (ADR), and possible risk factors in patients of rheumatoid arthritis administering methotrexate. And to determine the possibility of any new adverse drug reaction that is not well explored in previous studies. An observational follow up study designed and conducted using Naranjo scale to identify the adverse drug reactions in rheumatoid arthritis patients administering methotrexate in KIM’s Hospital.  The objective is to identify the dose dependent adverse drug reactions in rheumatoid arthritis patients and identify possible risk factors associated adverse drug reactions of methotrexate of methotrexate. Toxic effects may occur hours, to days to weeks after methotrexate administration and or overdose, the purpose of this study is to determine the relation between the dose and the occurrence of adverse drug reaction of methotrexate. During the study period clinically relevant adverse drug reaction have been presented by the patients taking methotrexate who attended hospital for their regular checkup. For example, the most commonly reported adverse drug reaction is abnormal taste for food and other less commonly presented adverse drug reaction include diarrhea, constipation, nausea, vomiting, and alopecia. In female patient’s 20-49 age group reported adverse drug reaction like amenorrhea, dysmenorrhea. Methotrexate toxicity develops due to increased patient susceptibility during the treatment.