Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

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.

RESUMO Recentes avanC'os em sistemas de liberaC'C#o de fC!rmacos novos visam C obtenC'C#o de melhor adesC#o do paciente. Um destes avanC'os C) a formulaC'C#o de comprimidos de desintegraC'C#o oral (ODTs), que se dissolvem instantaneamente, liberando o fC!rmaco, em alguns segundos, sem a necessidade de C!gua. O principal objetivo deste trabalho foi preparar e desenvolver ODTs de clopidogrel. Os ODTs foram preparados pelo mC)todo de compressC#o direta. Estudou-se o efeito de vC!rias concentraC'C5es de diferentes agentes de desintegraC'C#o, tais como super-crospovidona, croscarmelose de sC3dio, glicolato de amido de sC3dio no tempo de desintegraC'C#o e velocidade de dissoluC'C#o. Os comprimidos preparados foram avaliados quanto C dureza, C friabilidade, ao tempo de desintegraC'C#o e C liberaC'C#o do fC!rmaco in vitro. AlC)m disso, estudou-se a interaC'C#o de clopidogrel com os excipientes de formulaC'C#o, utilizando calorimetria de varredura diferencial (DSC). Estudos de DSC revelaram nC#o haver interaC'C#o entre o fC!rmaco e os excipientes utilizados. Todos os comprimidos possuC-am dureza na faixa de 4,0-5,2 kp e a friabilidade inferior a 1%. A variaC'C#o de peso e o teor de fC!rmaco de todas as formulaC'C5es mostraram-se dentro do limite oficial, de acordo com a BP. O estudo de liberaC'C#o do fC!rmaco in vitro de comprimidos ODTs mostrou que mais de 90% do fC!rmaco foram liberados em10 minutos. O teste de palatabilidade em voluntC!rios humanos mostrou sabor e sensaC'C#o na boca aceitC!veis. Assim, os resultados obtidos demonstraram, conclusivamente, a rC!pida e bem-sucedida desintegraC'C#o dos comprimidos formulados e a palatabilidade aceitC!vel.