Development of enteric coated sustained release minitablets containing mesalamine

O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por minicomprimidos com sistema matricial de liberação prolongada revestidos com polímero de liberação pH-dependente, utilizando mesalazina como fármaco modelo. Polyox® WSR 1105 foi o polímero utilizado no sistema matricial e Eudragit® L30D55 foi utilizado como polímero pH-dependente. Os minicomprimidos (com 20%, 30% e 40% de concentração de Polyox®) foram preparados por granulação via seca, gerando minicomprimidos de boa qualidade. Os minicomprimidos desenvolvidos foram revestidos em leito fluidizado a 8% de nível de revestimento. Efetuou-se o estudo de dissolução em meios que simulam o trato gastrointestinal (pH 1,4, 6,0 e 7,2) e as formulação contendo maiores concentrações de Polyox® foram capazes de reter a liberação do fármaco em pH 1,4. Todas as três formulações apresentaram liberação prolongada e comportamento cinético de ordem zero. O modelo de liberação de Korsmeyer-Peppas mostrou que as formulações com 20% e 30% de polímero apresentam comportamento de transporte anômalo, enquanto a com 40%, transporte super caso II. A eficiência de dissolução mostrou que somente as formulações com 20% e 40% de concentração do polímero foram consideradas estatisticamente diferentes.The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer, using mesalamine as a model drug. Polyox® WSR 1105 was the polymer used in the matrix system and Eudragit® L30D55 was used as a pH-dependent polymer. The minitablets (with 20%, 30% or 40% Polyox® concentration) were prepared by dry granulation, which led to good quality minitablets. The developed minitablets were coated in a fluidized bed at 8% of the coating level. Dissolution studies were performed in media that simulated the gastrointestinal tract (pH 1.4, 6.0 and 7.2) and showed that formulations with higher Polyox® concentrations were capable of retaining the drug release in pH 1.4. All formulations prolonged the drug release and presented zero-order kinetic behaviour. The Korsmeyer-Peppas model demonstrated that formulations with 20% or 30% of polymer exhibited anomalous transport behaviour, whilst the 40% sample exhibited super case II model transportation. Dissolution efficiency showed that only the formulations containing 20% and 40% polymer could be considered statistically different

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por mini-comprimidos revestidos com polímero de liberação pH-dependente, utilizando como fármaco modelo o omeprazol. Os mini-comprimidos (diâmetro de 2,5 mm) foram obtidos em máquina de compresssão excêntrica, revestidos em leito fluidizado com hidroxipropilmetilcelulose/Eudragit(r)L30D55 e, em seguida, acondicionados em cápsulas gelatinosas duras. A partir dos resultados obtidos no perfil de dissolução foi possível demonstrar a liberação gastro-resistente e comportamento cinético de ordem zero. A formulação contendo lactose como diluente, com revestimento de 12% de polímero, demonstrou semelhança com o medicamento referência.The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r) L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain) of polymer was similar to that ofthe reference drug

In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.Para exercer ação farmacológica, medicamentos tópicos de aplicação cutânea precisam, primeiramente, liberar o fármaco do veículo, para que desta forma ele se torne disponível para penetração nas camadas da pele, até atingir seu local de ação. A liberação do fármaco do veículo depende principalmente das características da formulação. Até a presente data, para registrar um medicamento genérico ou similar no Brasil não se exigem testes de desempenho para produtos tópicos de ação local. O presente trabalho teve como objetivo avaliar a liberação in vitro de especialidades farmacêuticas de diclofenaco dietilamônio gel do mercado farmacêutico brasileiro, usando o sistema de célula de difusão vertical. Avaliaram-se fatores que influenciam o teste como o tipo de membrana usada nos ensaios de liberação e características da formulação que impactam a velocidade de difusão. A legislação vigente no País permite que medicamentos genéricos contenham excipientes diferentes do medicamento referência. Esta diferença afetou a liberação do fármaco do veículo. Dos quatro medicamentos genéricos testados apenas um seria considerado equivalente ao medicamento referência Cataflam Emulgel®. As membranas de acetato de celulose e polietersulfona testadas apresentaram-se intercambiáveis nos estudos de liberação desse produto

Development and evaluation of multiparticulate biphasic system for the treatment of circadian diseases

Multiparticulate systems have biopharmaceutical advantages when compared to the monolithic systems, once they allow different patterns of drug release and can be used in different treatments. The aim of the present work was to develop a biphasic controlled release delivery system, using propranolol hydrochloride (PROP) that can be used for the treatment of circadian diseases. This system was obtained by the combination of cellulosic polymers hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) in a 2² factorial experimental design, which allowed the optimization of the development stage. The pellets produced and used in biphasic formulations were evaluated for physical and chemical characteristics and presented acceptable results. The immediate fraction obtained showed the complete release in 30 min while the others kept the release of the drug for 24 h. This study showed that the combination of beads with different releasing characteristics allowed to obtain different release profiles, which can be modulated according to the pathological needs, especially with regard to circadian diseases that suffer alterations throughout the day

Permeação cutânea in vitro do ácido kójico

Disorder of the tirosinase biosynthesis process can result on hiperpigmentations, like the frequently found melasma. The kojic acid is one of the depigmenting topic agent utilized in the handling of these hipercromies. The action of a dermatologic product should be topic, should not reach systemic levels. One of the factors that is able to defined the level of action, topic or systemic, is the vehicle. In this contest, the present work had for objective evaluate the rank of in vitro cutaneous permeation, in the cell of FRANZ modified, of a formulation regarding a buffered solution 7.4, both containing kojic acid (2%). The kojic acid percutaneous penetration and retention was quantified by a spectrophotometric in the ultraviolet method. The in vitro study showed that the absorption of kojic acid from the formulation presented kinetic of pseudo 1st order (in the break from 1 to 8 hours) and consequently smaller stream through the natural membrane (skin from the ear of pig) and bigger cutaneous retention, while the kojic acid from the buffered solution pH 7.4 presented kinetic of zero order and consequently bigger stream and smaller retention. This result indicated that the formulation developed can be used as a vehicle for kojic acid, having in mind that the target tissue is the skin.Desordens no processo melanogênico podem causar as hiperpigmentações, sendo a de maior freqüência o melasma. O ácido kójico é um dos despigmentantes tópicos utilizados no tratamento destas hipercromias. A ação de um produto dermatológico deve ser tópica, não devendo atingir níveis sistêmicos. Um dos fatores que pode definir o nível de ação, tópica ou sistêmica, são os excipientes das formulações. Neste contexto, o presente trabalho teve por objetivo avaliar o grau de permeação cutânea in vitro, utilizando célula de FRANZ modificada, de uma formulação em relação a uma solução tampão pH 7,4, ambas contendo ácido kójico na concentração de 2%. A quantificação do ácido kójico permeado e retido na membrana foi realizada por método espectrofotométrico no ultravioleta. O estudo in vitro mostrou que a absorção do ácido kójico da formulação apresentou cinética de pseudo 1ª ordem (no intervalo de 1 a 8 horas) e, conseqüentemente, menor fluxo através da membrana natural (pele da orelha de porco) e maior retenção cutânea, enquanto que o ácido kójico da solução tampão pH 7,4 apresentou cinética de ordem zero e, conseqüentemente, maior fluxo e menor retenção. Este resultado indicou que a formulação desenvolvida mostrou-se adequada para a veiculação do ácido kójico, tendo em vista que o órgão alvo é a pele

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r) L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain) of polymer was similar to that ofthe reference drug

Development of enteric coated sustained release minitablets containing mesalamine

The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer, using mesalamine as a model drug. Polyox® WSR 1105 was the polymer used in the matrix system and Eudragit® L30D55 was used as a pH-dependent polymer. The minitablets (with 20%, 30% or 40% Polyox® concentration) were prepared by dry granulation, which led to good quality minitablets. The developed minitablets were coated in a fluidized bed at 8% of the coating level. Dissolution studies were performed in media that simulated the gastrointestinal tract (pH 1.4, 6.0 and 7.2) and showed that formulations with higher Polyox® concentrations were capable of retaining the drug release in pH 1.4. All formulations prolonged the drug release and presented zero-order kinetic behaviour. The Korsmeyer-Peppas model demonstrated that formulations with 20% or 30% of polymer exhibited anomalous transport behaviour, whilst the 40% sample exhibited super case II model transportation. Dissolution efficiency showed that only the formulations containing 20% and 40% polymer could be considered statistically different