Estudo termoanalítico e de compatibilidade fármaco-excipiente de rifampicina e alguns medicamentos utilizados na terapêutica da tuberculose / Thermoanalytical study and drug-excipient compatibility of rifampicin and some medicines utilized in tuberculosis terapeutics

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

This work was aimed at implementing the thermal analysis and other physico-chemical and analytical techniques in the development and quality control of drugs and medicines for the treatment of tuberculosis, especially rifampicin. The differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry(TG/DTG), elemental analysis, X-ray diffraction (XRD) and infrared spectrometry (IR) were the main tools used. These techniques allowed to: evaluate thermal stability and the process of thermal decomposition of rifampicin and excipients used in pharmaceutical formulations; distinguish the two types of polymorphic forms; develop studies to establish kinetic parameters and evaluate the possible interactions between rifampicin and excipients. The studies were developed using two rifampicin samples, identified as polymorphs I and II. The elemental analysis results showed that both samples have the same composition and stoichiometry (C43H58N4O12), characteristic of the drug in question. IR spectra of both samples are very similar, but with little differences due to variations in the molecular conformation of polymorphic forms. These differences are clear when the absorption bands of ansa-OH, furanone and acetyl groups are compared in both spectra. XRD patterns showed that the two samples are crystalline and that they are two distinct structures. TG/DTG curves showed that polymorph I is more thermally stable than polymorph II. DSC curves confirm the TG/DTG results and allow to clearly differentiate a polymorphic form of the other. DSC curve of the polymorph II shows that initially occur the melting process, followed by crystallization and formation of polymorph I, which then is thermally decomposed. IR spectrum of the product isolated after recrystallization of polymorph II confirms the conversion to polymorph I. After Isothermal and non-isothermal kinetic studies by TG, it was possible to calculate, in both cases, the activation energy envolved in the thermal decomposition of each polymorph. The pre-formulation studies, using physical mixtures in the proportion 1:1 drug/excipient, indicated that there is interaction between the polymorph II and PEG 6000 and Lutrol F68. The excipients melt and dissolve the drug, which is converted to polymorph I. The drug-drug compatibility studies of rifampicin and isoniazid showed that there is interaction with both polymorphs. It appears that the interaction between the species leads to formation of the 3-(isonicotinylhydrazinmethyl) rifamycin compound. The evaluation of thermoanalytical profiles of commercial products allowed the identification of the polymorph was used in the formulation. It was possible to conclude that DSC tests identify the rifampicin polymorph used in association with isoniazid.

ASSUNTO(S)

dsc dsc thermal analysis thermogravimetry análise térmica termogravimetria

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