RESUMO
Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.
Assuntos
Boca/patologia , Candidíase Bucal/tratamento farmacológico , Alimentos/classificação , Liofilização/classificação , Gengiva/anormalidadesRESUMO
Aim: Understanding a drug dissolution process from solid dispersions (SD) to develop formulations with predictable in vivo performance. Materials & methods: Dissolution data of fenbendazole released from the SDs and the control physical mixtures were analyzed using the Lumped mathematical model to estimate the parameters of pharmaceutical relevance. Results: The fit data obtained by Lumped model showed that all SDs have a unique dissolution profile with an error of ±4.1% and an initial release rate 500-times higher than the pure drug, without incidence of drug/polymer ratio or polymer type. Conclusion: The Lumped model helped to understand that the main factor influencing the fenbendazole release was the type formulation (SD or physical mixture), regardless of the type or amount of polymer used.
Assuntos
Fenbendazol , Preparações Farmacêuticas , Liberação Controlada de Fármacos , Polímeros , SolubilidadeRESUMO
BACKGROUND: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing. OBJECTIVE: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen. METHODS: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate. RESULTS: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight. CONCLUSION: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.
Assuntos
Desenvolvimento de Medicamentos , Cetoprofeno/síntese química , Administração Oral , Composição de Medicamentos , Humanos , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Tamanho da Partícula , Controle de Qualidade , Solubilidade , Propriedades de Superfície , Comprimidos , Fatores de TempoRESUMO
Benznidazole (BNZ) is the drug of choice for the treatment of Chagas disease in many countries. However, its low water solubility produces low and/or variable oral bioavailability. Thus, the aim of this work was to formulate micro- and nanoparticles based on Eudragit® RS PO and Eudragit® RL PO as a convenient approach to increase the dissolution rate of BNZ. The microparticles were obtained by means of spray-drying process while the nanoparticles were prepared through the nanoprecipitation technique and further freeze-drying. The results indicated that nanoparticles were obtained in 86% yield while microparticles were obtained in 68% yield. In both cases, the encapsulation efficiency of particles was greater than 78% while drug loading capacity was nearly 24% w/w and 18% w/w, after spray-drying and freeze-drying procedures, respectively. Images of scanning electron microscopy showed that the particles obtained by spray-drying and freeze-drying were in the micrometer and nanometer scale, respectively. FT-IR spectra of BNZ-loaded particles obtained by both methods showed characteristic bands of BNZ confirming that part of drug remained on their surface. Thermal analysis revealed that the drug crystallinity after both methods decreased. Physical stability evaluation of the nanoparticles confirmed that Pluronic® F68 was suitable to keep the particles size in a range of 300 nm after 70 days storage at 4 ± 2 °C. In-vitro release studies showed increased dissolution rate of drug from the particles obtained by both methods respect to untreated BNZ. The kinetics of drug release in acid media followed the Higuchi kinetics indicating drug diffusion mechanism from particles.
Assuntos
Doença de Chagas/tratamento farmacológico , Imunossupressores/química , Imunossupressores/uso terapêutico , Nanopartículas/química , Nitroimidazóis/química , Nitroimidazóis/uso terapêutico , Criança , Liberação Controlada de Fármacos , Humanos , Hidrodinâmica , Imunossupressores/síntese química , Cinética , Nitroimidazóis/síntese química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
AIM: Solid dispersions using Poloxamer 407 as carrier were developed to improve albendazole (ABZ) solubility and dissolution profiles. METHODS: ABZ/poloxamer solid dispersions were prepared, and dissolution profiles were mathematically modeled and compared with physical mixtures, pharmaceutical ABZ and a commercial formulation. RESULTS: Poloxamer 407 increased exponentially ABZ solubility, in about 400% when 95% w/w of polymer compared with its absence. Solid dispersions initial dissolution rate was three to 20-fold higher than physical mixtures, the drug and the commercial formulation. All the solid dispersions required less than 2.2 min to reach an 80% of ABZ dissolution, while the commercial formulation needed around 40 min. CONCLUSION: Solid dispersions improved ABZ solubility and dissolution rate, which could result in a faster absorption and an increased bioavailability.
Assuntos
Albendazol/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Poloxâmero/química , Absorção Fisico-Química , Albendazol/administração & dosagem , Albendazol/química , Disponibilidade Biológica , Química Farmacêutica , Composição de Medicamentos/métodos , SolubilidadeRESUMO
ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.
Assuntos
Solubilidade , Flurbiprofeno/análise , Dissolução , Comprimidos/classificação , Preparações FarmacêuticasRESUMO
The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation). Dissolution efficiency (DE%) was calculated for both formulations to evaluate their
O objetivo do presente estudo foi avaliar a bioequivalência de duas formulações de cefalexina disponíveis no mercado brasileiro (produto A como formulação referência e produto B como formulação teste). A eficiência de dissolução (DE%) foi calculada para ambas as formulações para avaliar suas características biofarmacêuticas. O estudo de bioequivalência oral foi realizado em vinte e quatro voluntários sadios utilizando um desenho cruzado. Uma dose oral única (comprimido contendo 500 mg de cefalexina) de cada produto foi administrada com um período de
Assuntos
Humanos , Cefalexina/farmacocinética , Cefalexina/farmacologia , Cromatografia Líquida de Alta Pressão , Equivalência Terapêutica , Urina/químicaRESUMO
Introducción: la deficiencia de minerales en la población está asociada a enfermedades metabólicas, hormonales e inmunológicas. Usualmente, los minerales son suplementados en el organismo en forma de sales inorgánicas, las cuales pueden causar molestias gástricas y baja absorción en dependencia del tipo de sal empleado. Estudios previos muestran una adecuada absorción y ausencia de efectos gástricos cuando los minerales están asociados a ligandos orgánicos como enzimas, proteínas y particularmente aminoácidos. Objetivo: determinar mediante un estudio de preformulación la viabilidad de utilizar asparaginatos de cobre, magnesio, manganeso y zinc en suplementos nutricionales. Métodos: se realizó la síntesis y la verificación de formación de los complejos por espectroscopia infrarroja por transformada de Fourier y difracción de rayos X de polvos. Se evaluó la solubilidad, la constante de disociación, la eficiencia de la disolución y las propiedades físicas del estado sólido (morfología, distribución y tamaño de partícula, índice de Haussner, porosidad y compresibilidad) de los complejos. Se determinó la compatibilidad de los complejos con excipientes. Resultados: en los espectros infrarrojos se observó la participación del grupo carboxilo de la asparagina en la formación del enlace de coordinación de los complejos. En los difractogramas de rayos X se mostró la ausencia de los materiales de partida y la cristalinidad en los complejos. La solubilidad, la constante de disociación y la eficiencia de la disolución de los complejos, establecieron su carácter anfótero. Conclusiones: los resultados en las propiedades físicas del estado sólido, la humedad y la compatibilidad con excipientes, establecen que las formulaciones de los aparaginatos de cobre, magnesio, manganeso y zinc tienen propiedades reológicas adecuadas para propósitos farmacéuticos.
Introduction: the mineral deficiency in the human population has been associated with metabolic, hormonal and immunological disorders. These minerals are generally supplemented with inorganic salts in the body, but they might cause gastric distress and low absorption problems depending on the type of salt used. Previous studies demonstrated adequate absorption and absence of gastric effects when minerals were associated with organic ligands such as enzymes, proteins and particularly amino acids. Objective: to determine the viability of copper, magnesium, manganese and zinc asparaginates as nutritional supplements in a preformulation study. Methods: the synthesis and verification of the formation of complexes were carried out by Fourier transformed infrared spectroscopy and X-ray diffraction of powders. The solubility, the dissociation constant, the dissolution efficiency and the physical solid state properties (morphology, particle distribution and size, Haussner´s index, porosity and compressibility) of these complexes were evaluated. The compatibility of the complex with excipients was determined. Results: the involvement of the asparagine carboxyl group in the formation of the coordination bond of the complex was observed in the infrared spectra. the absence of starting materials and the crystallinity in the complexes were evidenced in the X-ray diffraction of powders. The solubility, the dissociation constant and the dissolution efficiency of the complexes established their amphoteric character. Conclusions: the results achieved in the physical solid state properties, the level of moisture and the compatibility with the formulation excipients indicate that copper, magnesium, manganese and zinc asparaginates have suitable rheological properties for pharmaceutical purposes.
RESUMO
In this study, fluid bed granulation was applied to improve the dissolution of nimodipine and spironolactone, two very poorly water-soluble drugs. Granules were obtained with different amounts of sodium dodecyl sulfate and croscarmellose sodium and then compressed into tablets. The dissolution behavior of the tablets was studied by comparing their dissolution profiles and dissolution efficiency with those obtained from physical mixtures of the drug and excipients subjected to similar conditions. Statistical analysis of the results demonstrated that the fluid bed granulation process improves the dissolution efficiency of both nimodipine and spironolactone tablets. The addition of either the surfactant or the disintegrant employed in the study proved to have a lower impact on this improvement in dissolution than the fluid bed granulation process.