Baclofeno: Desenvolvimento e controle da qualidade de comprimidos de liberação modificada

Abstract

Spasticity is a disorder characterized by an increase in velocity-dependent tonic stretch reflexes. Baclofen is the therapy of first choice in the treatment of spasticity, however it has a short half-life that varies from two to four hours, requiring its administration several times a day. Therefore, this study aimed to develop modified-release tablets with baclofen for the treatment of spasticity. On account of, three batches of tablets containing baclofen were developed and characterized as to their modified release capacity. The compatibility study between the pharmaceutical excipients and baclofen was carried out by Differential Thermal Analysis (DTA), Thermogravimetry (TG) and Fourier Transform Infrared Spectroscopy (FTIR), in addition to the quality control of the powders and obtaining the average weight, hardness, friability, disintegration and in vitro release of the tablets. The results indicated incompatibility of baclofen with starch and colloidal silicon dioxide. The flow of the powders was unsatisfactory, so the granulate was produced using the wet method. All granulated formulations presented an angle of repose below 26º, thus characterizing the flow as excellent. Three batches of tablets with different controlled release polymers were obtained: F1 containing hydroxyethylcellulose (HEC), F2 containing poloxamer (PF127) and F3 containing the polymer blend of HEC and PF127, whose hardness ranged from 9.90 N up to 29.70 N. All formulations showed friability lower than 1.5% and average experimental weight between 268.20 and 272.60 mg, in addition to the content uniformity being in accordance with the Acceptance Values, with all parameters within the standards established by the Brazilian Pharmacopoeia. However, the in vitro release study demonstrated that the formulations were unable to prolong baclofen release, reaching release plateau within up to one hour. Due to the large amount of lactose, it acted as a catalyst for water penetration into the matrix pores, increasing tablet erosion. Due to this, it is necessary to modify development conditions, such as such as changing the diluent, modify concentration and type of polymer to improve the release profile.