Azathioprine is an immunosuppressive drug for several inflammatory disorders. Due to its clinical relevance, to explore the solid-state properties for excipient compatibility in the product quality review process is essential. Fourier transform infrared spectroscopy, powder X-ray diffraction and thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC)) were applied. The compatibility studies evidenced that starch pregelatinized, colloidal silicon dioxide, and talc are fully compatible with azathioprine. However, stearic acid, magnesium stearate, and mannitol are incompatible after heat supply at temperatures easily reached by industrial processing. The nonlinear Vyazovkin isoconversional treatment performed the kinetic study of the thermal degradation. The activation energies were determined to clarify the influence of each excipient on the thermal drug stability, an essential procedure in the pharmaceutical development, and all over the commercial live span, in Good Manufacturing Practices.

Thermal analysis can be used to determine shelf-life and kinetic parameters in pharmaceutical systems. This work investigates the kinetic of lumefantrine thermal decomposition, an antimalarial, using non-isothermal and isothermal experimental data. The non-isothermal conditions are analyzed applying Vyazovkin method, while isothermal conditions employ models fitting procedure and artificial neural network. Lumefantrine was characterized by powder X-ray diffraction and Fourier transform infrared spectroscopy. The initial stage of lumefantrine thermal decomposition, about 5% of conversion, corresponds to the loss of chlorine and hydroxyl, being correctly predicted by the neural network as a complex event. At room temperature, the D3 model is appropriate to describe the process, once the half-life time is 19 months, in agreement with manufacturer. Isoconversional model determined the activation energy along the whole process while isothermal methodology determined the global value considering the entire process. The results provide important information for the pharmaceutical industry to assay levels of acceptable lumefantrine contents.

Lamivudina e efavirenz estão entre os fármacos mais utilizados em todo o mundo para o tratamento da síndrome da imunodeficiência adquirida (AIDS). Foram utilizadas as técnicas de ressonância magnética nuclear de estado sólido (ssNMR), espectroscopia no infravermelho por transformada de Fourier (FTIR), calorimetria exploratória diferencial (DSC), e análise termo-óptica (TOA) para estudar possíveis interações entre esses fármacos, visando o desenvolvimento de uma combinação em dose fixa dos mesmos. DSC e TOA evidenciaram deslocamentos significantes das temperaturas de fusão dos fármacos na mistura, o que sugere uma interação entre eles. Apesar de os resultados de DSC e TOA indicarem incompatibilidade entre as drogas, os espectros de FTIR não apresentaram modificações devido à sobreposição de bandas. As análises de ssNMR mostraram mudanças significativas nos valores de deslocamento químico da mistura quando comparados aos dos fármacos puros, especialmente nos sinais referentes a átomos de carbono deficientes em elétrons. Essses resultados confirmam as interações sugeridas pelo DSC e TOA, devido provavelmente a interações ácido-base entre átomos eletronegativos e deficientes em elétrons dos fármacos.

Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz.