ABSTRACT
In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.
Subject(s)
Chemistry, Pharmaceutical/methods , Gliclazide/analysis , Gliclazide/chemistry , Delayed-Action Preparations/analysis , Delayed-Action Preparations/chemistry , Excipients/analysis , Excipients/chemistry , Solubility , Tablets/chemistryABSTRACT
Primaquine (PQ) is used for the radical cure of Plasmodium vivax malaria and can cause serious side effects in some individuals. The development of an extended-release dosage with poly(ethylene oxide) as a hydrophilic polymer has been investigated to improve drug efficacy and tolerability. The aim of this study was to evaluate in vivo a new extended-release formulation of PQ (60 mg). The formulation was administered to beagle dogs and plasma PQ concentrations were compared to a conventional immediate-release formulation of PQ (60 mg). The evaluation was carried out using a validated high-performance liquid chromatography method using solid-phase extraction. Total PQ exposure in beagle dogs was 2.2 times higher (area under curve of 12 193 versus 5678 ng h/ml) and the elimination half-life of PQ was a 19-fold greater (12.95 hours versus 0.68 hours) with the extended-release tablets compared with the immediate-release tablets. These findings suggest that the extended-release formulation of PQ merits further evaluation for the treatment of P. vivax malaria and/or chemoprophylaxis.
Subject(s)
Antimalarials/pharmacology , Malaria/drug therapy , Plasmodium vivax/drug effects , Polyethylene Glycols/pharmacology , Primaquine/pharmacology , Animals , Biological Availability , Delayed-Action Preparations/pharmacology , Dogs , Drug Carriers , Female , Malaria/blood , TabletsABSTRACT
Neste trabalho, avaliou-se a utilização da quitosana como matriz hidrofílica no desenvolvimento de comprimidos de liberação prolongada de captopril. Os comprimidos foram obtidos por compressão direta utilizando-a em diferentes proporções (10, 15, 20 e 25%). As formulações contendo quitosana foram comparadas com uma formulação de liberação imediata contendo croscarmelose. Os resultados obtidos nos ensaios de peso médio, friabilidade, dureza, uniformidade de conteúdo e doseamento indicaram que todos os comprimidos apresentavam características de qualidade condizentes com os limites especificados na Farmacopeia Brasileira. Os ensaios de dissolução evidenciaram um aumento do tempo de liberação do captopril com o aumento da proporção de quitosana na matriz, indicando que essas formulações apresentaram perfis de liberação prolongada do fármaco, especialmente a formulação contendo 25% de quitosana. Os valores dos coeficientes de correlação indicaram que os modelos cinéticos que melhor se ajustam ao perfil de dissolução das formulações avaliadas foram o modelo proposto por Higuchi (pH 1,2) e o de primeira ordem (pH 6,8).
In this study, chitosan was used as a hydrophilic matrix in the development of prolonged-release tablets of captopril. The tablets were obtained by direct compression, with the chitosan in various proportions (10, 15, 20 and 25%). The formulations were compared with an immediate-release formulation containing croscarmellose. In assessments of weight variation, friability, hardness, content uniformity and drug assay, all the tablets complied with the standards of quality set by the Brazilian Pharmacopoeia. Dissolution tests showed that the release time of captopril increased with the content of chitosan in the matrix, indicating that these formulations showed prolonged-release profiles of the drug, especially the one containing 25% chitosan. The kinetic models that fitted the dissolution profiles of the formulations best (with the highest correlation coefficients) were the Higuchi (at pH 1.2) and first-order (at pH 6.8) models.
