Estudos de pré-formulação, desenvolvimento analítico e avaliação da qualidade de cápsulas de acetato de fludrocortisona, acetato de cortisona e hidrocortisona base

Abstract

The quality of the drug is the degree to which it meets all the characteristics established from the research phase of the active molecule for its intended purpose until the drug is made available to the user. Corticosteroids, due to their intense immunomodulatory and anti-inflammatory activity, are the most widely prescribed drugs in the world. In Brazil, the commercialization of corticosteroids, registered in ANVISA, for oral solid pharmaceutical form, is restricted to the compressed pharmaceutical form. The capsule pharmaceutical form is handled in master pharmacies and there is no description in official compendiums and in the literature of standardized formulation for manipulation and no analysis methodologies for corticosteroids in this presentation. This work aimed to develop standardized formulations for pharmaceutical capsule form and to validate analytical methods for biopharmaceutical studies of fludrocortisone acetate, cortisone acetate and hydrocortisone base, as well as to study the scapability of standardized capsules and to characterize polymorphs in fludrocortisone acetate. The methods of analysis of these corticosteroids were validated, as well as their applications in the dissolution test, according to RDC 166/2017 - ANVISA / MS, presenting satisfactory results. After the IFA compatibility study with the proposed excipients, a factorial design was carried out in order to select a capsule formulation of each corticosteroid through its performance in the dosage tests, mean weight, dissolution and uniformity of doses. Tests for accelerated stability and photostability of the selected capsules were performed which revealed limited stability of the formulations. The polymorphism investigation was done only for fludrocortisone acetate, where in addition to the already described, two new polymorphs were characterized.