ABSTRACT
Polymorphism and particle size distribution can impact the dissolution behaviour and, as a consequence, bioavailability and bioequivalence of poorly soluble drugs, such as Efavirenz (EFV). Nevertheless, these characteristics do not explain some failures occurring in in vitro assays and in in vivo studies. EFV belongs to Class II and the High Activity Antiretroviral Therapy (HAART) is considered the best choice in the treatment of adults and children. EFV is a drug that needs bioequivalence studies for generic compounds. In this work, six raw materials were analyzed and two of them were utilized with human volunteers (in vivo assays or bioequivalence). All the routine pharmaceutical controls of raw materials were approved; however, the reasons for the failure of the bioequivalence assay could not be explained with current knowledge. The aim of this work was to study microstructure, a solid-state property of current interest in the pharmaceutical area, in order to find an explanation for the dissolution and bioequivalence behaviour. The microstructure of EFV raw materials was studied by Whole Powder Pattern Modelling (WPPM) of X-ray powder diffraction data. Results for different EFV batches showed the biorelevance of the crystalline domain size, and a clear correlation with in vitro (dissolution tests) and in vivo assays (bioequivalence).
Subject(s)
Anti-HIV Agents/chemistry , Benzoxazines/chemistry , Models, Biological , Reverse Transcriptase Inhibitors/chemistry , Alkynes , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/therapeutic use , Benzoxazines/pharmacokinetics , Benzoxazines/therapeutic use , Biological Availability , Calorimetry, Differential Scanning , Cyclopropanes , Drug Contamination , Drug Liberation , Humans , Kinetics , Microscopy, Electron, Scanning , Molecular Structure , Particle Size , Powder Diffraction , Powders , Reproducibility of Results , Reverse Transcriptase Inhibitors/pharmacokinetics , Reverse Transcriptase Inhibitors/therapeutic use , Spectroscopy, Fourier Transform Infrared , Surface Properties , Synchrotrons , Therapeutic EquivalencyABSTRACT
Um método analítico utilizando espectroscopia no ultravioleta (UV) foi desenvolvido e validado para quantificar o fármaco captopril em comprimidos de liberação prolongada. Os parâmetros utilizados no processo de validação foram: especificidade, linearidade e intervalo, precisão, exatidão e robustez. A linearidade no intervalo de 5.0 40.0 µg/mL apresentou um coeficiente de correlação de 0, 9998. Os excipientes das formulações não interferiram com a análise e a recuperação da amostra foi de 100, 20 ± 0,28 porciento. Todos os resultados foram satisfatórios e o método provou ser adequado para quantificar o captopril nos comprimidos de liberação prolongada
Subject(s)
Captopril , Spectrophotometry , TabletsABSTRACT
Knowing the characteristics of raw materials in pharmaceutical practice is both important and useful. Firstly, evaluating the physical-chemical properties of the substances that will be used must be the primary step for quality control in the pharmacy industry. This work aims at analyzing the physical-chemical characteristics of two nimodipine samples I and II derived from distinct laboratories through thermal analysis (DSC and TG/DTG), HPLC, crystallography, and microscopy. Thermal analysis showed that sample II was more unstable than I. Morphological differences concerning shape, size, and crystallinity of particles were visualized by scanning electron microscopy (SEM) and X-ray powder diffraction. To sum up, the techniques used in this study can be said to have been efficient in the characterization and evaluation of quality control of the raw material.
Subject(s)
Calcium Channel Blockers/chemistry , Nimodipine/chemistry , Calorimetry, Differential Scanning , Chromatography, High Pressure Liquid , Crystallization , Drug Stability , Microscopy, Electron, Scanning , Powder Diffraction , Quality Control , Thermogravimetry , Transition Temperature , X-Ray DiffractionABSTRACT
O estudo teórico e tecnológico de fármacos de liberação prolongada vem se difundido, principalmente nas últimas quatro décadas, o que pode ser confirmado pelo número de trabalhos publicados desde então. Medicamentos de liberação prolongada são utilizados com o objetivo de estender o período de ação farmacológica de uma substância terapêutica e/ou para liberar o fármaco em determinada local do organismo. A liberação estendida melhora a posologia de diversos fármacos otimizando a adesão ao tratamento. No entanto, nem todos fármacos são bons candidatos a este tipo de formulação, devendo este possuir características físico-químicas adequadas. Várias alternativas para o desenvolvimento e avaliação de apresentações de liberação prolongada são disponíveis. O objetivo deste trabalho é apresentar uma revisão acerca dos métodos utilizados na avaliação do mecanismo de liberação de fármacos a partir de sistemas de liberação prolongada. Para tanto modelos de análise dependentes e independentes são apresentados, bem como modelos estatísticos
