RESUMO
Mathematical models are an important tool in pharmaceutical formulations development, to evaluate in vitro and in vivo drug release processes and to optimize the design of new systems. Dome Matrix technology allows the combination of modules with different types of drugs, doses, and releases kinetics. This work aimed to design drug release systems based on Dome Matrix technology, with different swelling and erosion properties, to obtain complex drug release profiles and analyze them with simple mathematical models. Most of the release profiles followed a sigmoid curve, with an inflection point corresponding to a change in the release rate behavior. The experimental data were fitted with a simple model recently developed, named the Dual Release model, which consists in the combination of a modified Korsmayer-Peppas model from the beginning to the inflection point and the Lumped model from there until the end. This approach allowed determining relevant pharmaceutical parameters, such as the maximum release rate and the dissolution efficiency, among others. The use of the Dual Release model and the pharmaceutical parameters that characterize the different Dome Matrix modules allows optimizing the choice of the composition and the configuration during the development of a drug delivery system.
Assuntos
Sistemas de Liberação de Medicamentos , Tecnologia , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Cinética , Solubilidade , ComprimidosRESUMO
Benznidazole (BZL), the first line drug for Chagas disease treatment, presents a low solubility, limiting the possibilities for its formulation. In this work, solid dispersions' (SDs) technology was exploited to increase BZL kinetic solubility and dissolution rate, seeking for an improvement in its bioperformance. A physical mixture (PM) and an SD using Poloxamer 407 as carrier were prepared and characterized. Dissolution tests were performed, and data were analyzed with the lumped model, which allowed to calculate different parameters of pharmaceutical relevance. A bioactivity assay was also carried out to probe the SD anti-trypanocidal activity. Among the most relevant results, the initial dissolution rate of the BZL SD was near 3, 4 and about 400-fold faster than the PM, a commercial formulation (CF) and an extracted BZL, respectivley. The times needed for an 80% of drug dissolution were 3.6 (SD), 46.4 (PM), and 238.7 min (CF); while the dissolution efficiency values at 30 min were 85.2 (SD), 71.2 (PM), and 65.0% (CF). Survival curves suggested that using Poloxamer 407 as carrier did not alter the anti-trypanocidal activity of BZL. These results allow to conclude that SDs can be an effective platform for immediate release of BZL in an oral administration.
Assuntos
Portadores de Fármacos/química , Nitroimidazóis/administração & dosagem , Nitroimidazóis/química , Poloxâmero/química , Tripanossomicidas/administração & dosagem , Tripanossomicidas/química , Administração Oral , Doença de Chagas/tratamento farmacológico , Liberação Controlada de Fármacos , Humanos , Nitroimidazóis/farmacologia , Solubilidade , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Difração de Raios XRESUMO
Poly(3-hydroxybutyrate) (PHB) biodegradable polymeric membranes were evaluated as platform for progesterone (Prg)-controlled release. In the design of new drug delivery systems, it is important to understand the mass transport mechanism involved, as well as predict the process kinetics. Drug release experiments were conducted and the experimental results were evaluated using engineering approaches that were extrapolated to the pharmaceutical field by our research group. Membranes were loaded with different Prg concentrations and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). SEM images showed that membranes have a dense structure before and after the progesterone addition. DSC and FTIR allowed determining the influence of the therapeutic agent in the membrane properties. The in vitro experiments were performed using two different techniques: (A) returning the sample to the receptor solution (constant volume of the delivery medium) and (B) extracting total volume of the receptor solution. In this work, we present a simple and accurate "lumped" second-order kinetic model. This lumped model considers the different mass transport steps involved in drug release systems. The model fits very well the experimental data using any of the two experimental procedures, in the range 0 ≤ t ≤ ∞ or 0 ≤ M t ≤ M ∞. The drug release analysis using our proposed approaches is relevant for establishing in vitro-in vivo correlations in future tests in animals.
Assuntos
Ácido 3-Hidroxibutírico/química , Hidroxibutiratos/química , Poliésteres/química , Progesterona/química , Varredura Diferencial de Calorimetria/métodos , Sistemas de Liberação de Medicamentos/métodos , Cinética , Microscopia Eletrônica de Varredura/métodos , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
The aim of this work was the development of extended release tablets of 500 mg of ciprofloxacin based on swellable drug polyelectrolyte matrices (SDPM). A set of complexes of carbomer, ciprofloxacin and sodium, (CB-Cip)(50)Na( x ), having a molar ratio Cip/CB acid groups of 0.5 and variable proportions of Na(+) was used to prepare SDPM. Characterization of complexes by FT-IR, powder X-ray diffraction and thermal analysis revealed that Cip, in its protonated form, is ionically bonded to the functional groups of CB. Rates of fluid uptake of (CB-Cip)(50)Na( x ) matrices as well as Cip release in simulated gastric fluid were modulated by changes in the proportion of Na(+) incorporated in the complexes. A direct correlation between fluid uptake and delivery rate was observed along the series of matrices. Release rates were modulated from 1.4 mg/min to 25 mg/min in going from (CB-Cip)(50)Na(10) to (CB-Cip)(50)Na(14). The analysis of kinetic data suggest that rates of swelling, ionic pair dissociation and drug diffusion play a role in the kinetic control of delivery. Complexes were satisfactorily prepared and processed together with small amounts of antiadherent and lubricant excipients to obtain a series of extended release SDPM tablets through the current tableting technology processes. Cip release from matrices was widely modulated by the composition of the complexes yielding a flexible system that allows selecting a composition that releases in 120 min 90% of the dose in simulated gastric fluid.