Compatibility study of hydroxychloroquine sulfate with pharmaceutical excipients using thermal and nonthermal techniques for the development of hard capsules
Hydroxychloroquine is effectively used in the treatment for malaria, lupus erythematosus and rheumatoid arthritis. The study of drug–excipient compatibility is an important tool for the development of safe and effective pharmaceutical forms. The present study describes the use of thermal and nonthermal techniques for evaluating the physicochemical compatibility of hydroxychloroquine with excipients for the development of solid dosage forms, including microcrystalline cellulose, corn starch, mannitol, magnesium stearate and colloidal silicon dioxide. The analytical techniques employed to evaluate the drug and the drug–excipient interactions in solid binary mixtures (1:1 w:w) were differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy (FTIR) and isothermal stress test. Four different formulations were prepared and drug dissolution test was determined by rotating-basket system method in water. Evidence of solid-state interactions of hydroxychloroquine and mannitol, magnesium stearate and colloidal silicon dioxide was observed in the DSC analysis and subsequently confirmed by FTIR; however, no degradation profile was observed by HPLC and no interference was seen in the drug dissolution rate and no change in physicochemical properties of hydroxychloroquine was observed. The combination of techniques is very important to correctly identify drug–excipients incompatibilities in the earliest stage of a formulation design in order to ensure the choice of suitable excipients for the development of stable and effective dosage forms of hydroxychloroquine.
KeywordsThermal analysis DSC TG FTIR Isothermal stress test Compatibility study
This work was financially supported by the following Brazilian research funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Pesquisas (FINEP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Financing code 001), Fundação de Apoio à Pesquisa da Universidade Federal de Goiás (FUNAPE) and Laboratório Central de Saúde Pública (LACEN-GO).
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