Formulation and evaluation of orally disintegrating clopidogrel tablets

ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability

UTILIZAÇÃO DA PRÓPOLIS E ÁLCOOL ETÍLICO NO CONTROLE DE Salmonella EM RAÇÕES AVÍCOLAS

Em quatro experimentos foram avaliados como agentes antibacterianos os produtos própolis em solução alcoólica e álcool etílico, adicionados às rações artificialmente contaminadas com os respectivos sorotipos: Salmonella typhimurium Nalr - Specr, (resistentes ao ácido Nalidíxico e a Spectinomicina) nos três primeiros experimentos e Salmonella agona Nalr - Specr, Salmonella infantis Nalr - Specr e Salmonella enteritidis Nalr - Specr no quarto experimento. As rações foram fornecidas a grupos de 10-16 pintos de corte de um dia. Em todos os experimentos os produtos testados foram adicionados na base de 2% da ração. Quando se utilizou solução hidroalcóolica de própolis (exp. 1), seguidas 120 horas após o desafio, detectou-se a presença da bactéria nos cecos. No segundo experimento, testou-se a solução de própolis e seu diluente, o álcool etílico; seguidas 96 horas após o desafio, não foi observada a presença da bactéria nos cecos (< 2,0 log10). Avaliou-se, no terceiro experimento, a ação da solução de própolis e do álcool etílico no tempo, adicionados na ração 14 dias e 28 dias antes do fornecimento às aves. Após 72 horas do desafio, a leitura nas placas acusou a presença da bactéria nos cecos. Dentro deste último período, também se avaliou a ação da própolis em pó (extrato seco) e esse mesmo extrato em uma solução aquosa, adicionados à ração 48 horas antes do fornecimento às aves sendo que os resultados confirmaram a presença da bactéria nos cecos. No quarto experimento avaliou-se somente o álcool etílico nas rações artificialmente contaminadas com os sorotipos S. agona, S. enteritidis e S. infantis, registrando-se contagem zero (<2,0 log10) apenas com o último sorotipo. Os resultados obtidos permitem concluir que o tratamento com a solução de própolis apresentou ação sobre a S. typhimurium somente quando em solução alcóolica, dentro de um período de 48 horas, indicando que o efeito bactericida se deveu ao álcool etílico presente na solução. A ação do tratamento com o álcool etílico sobre os demais sorotipos demonstrou resultado parcial sendo observado efeito bactericida nos sorotipos S. typhimurium e S. enteritidis artificialmente inoculados na ração.<br>Four similar trials were conducted to evaluate the effects of dietary inclusion of an alcoholic solution of propolis and ethyl alcohol on the control of salmonella artificially added to the feed offered to groups of 10-16 day-old broiler chicks. Salmonella typhimurium Nalr - Specr (resistant to Nalidixic acid and Spectinomicin) were used in the first three experiments and Salmonella enteritidis Nalr - Specr in the fourth. In every experiment the antibacterial agent was added in the proportion of 2%of the feed. When using hydroalcoholic solution of propolis (experiment 1), 120 hours after the challenge on the chicks, the presence of bacteria was in detected cecal contents. In the next experiment (experiment 2) an alcoholic solution of propolis and ethyl alcohol was tested: 96 hours after the challenge on the chicks the presence of bacteria in cecal content of the birds was not observed (< 2.0 log10 FCU/g). In the third experiment, a propolis solution and ethyl alcohol was evaluated when added to the feed 14 days and 28 days before the chicks consumed the experimental ration. Seventy-two hours after the chicks consumed the Salmonella contaminated ration, the plaque counts showed the presence of bacteria in cecal contents of the chicks. Within the last period (72 hours), a powdered propolis sample was evaluated (dehydrated extract) and, this extract in an aqueous solution, added to the feed 48 hours before the birds started ration consumption; the results confirmed the presence of the bacteria in cecal contents. In the fourth experiment, only ethyl alcohol in the feed artificially contaminated with the following serotypes: S. agona, S. enteritidis and S. infantis was evaluated . The results indicated zero count (< 2.0 log10 , FCU/g) only with the last serotype. Under this experimental conditions, propolis showed action over S. typhimurium only when in alcoholic solution and 48 hours before the birds consumed the contaminated ration, showing that bactericidal effect was due to ethyl alcohol present in the solution rather than to the propolis action per se. Ethyl alcohol showed bactericidal effect over two of the serotypes S. typhimurium and S. enteritidis artificially added to the feed, pointing that a standardized response did not occur