Desenvolvimento e validação de métodos para determinação de tacrolimus em cápsulas

Abstract

Tacrolimus is a lactone macrolide, derived from Streptomyces tsukubaensis. It is an immunosuppressive drug that has been used in the prevention of organs transplant rejection, such as liver, kidney, heart, small intestine, pancreas and bone marron. The drug is also indicated for the treatment of atopic dermatitis, eczema, psoriasis and vitiligo. It is available as capsules, injection and ointment. Few methods have been reported for tacrolimus quantification in the dosage forms. In the present work, spectrophotometric methods were developed and validated for quantification of the drug in capsules. One method was based on the reaction with concentrated sulfuric acid (98 %), with detection at 295 nm. The other method was based in the charge transfer complex with 0.01M Iodine, with detection at 365 nm. The methods showed good linearity (r>0,99), precision (<0,2%) and accuracy (>99%). Preliminary study for in vitro drug release was also performed. Different dissolution medium (phosphate buffer pH 6.8, acetate buffer pH 5.5 and 0.1M HCl) and different stirring rotate (75 and 100 rpm) were evaluated to select the conditions for dissolution test, using basket apparatus. The percents of drug dissolved were evaluated by high performance liquid chromatographic method described in the literature. The percentage of drug dissolved was more than 85 in 60 minutes.