Application of a quality-by-design approach for utilizing sodium stearyl fumarate as a taste-masking agent in dextromethorphan hydrobromide orally disintegrating tablets.

Orally dissolving tablets (ODTs) represent one of the recent advances in drug delivery. The foremost objective of this study was to optimize the utilization of lubricant sodium stearyl fumarate in the preparation of dextromethorphan hydrobromide ODTs with enhanced taste-masking properties. The simple blending of sodium stearyl fumarate with the powder bed would result in taste-masking through physical adsorption of the lubricant particles on the drug particles. A randomized 32 full factorial experimental design was used to characterize the relationship between lubricant ratio (X1), mixing time (X2), and the tablet properties. The tablets were assessed for friability, hardness, disintegration time, and in-vitro dissolution. All tablets showed hardness within the range of 3.0-3.7 kp, and the % loss in friability test was less than 1.1%. The in-vitro disintegration time ranged between 9 and 25 s. An in-vitro drug release study of the prepared ODTs showed that more than 90% of the drug was released within 30 min. A palatability test of the optimized formula conducted in human volunteers showed acceptable taste and mouthfeel with in-vivo disintegration time of 17 s. Thus, results obtained convincingly showed successful fast disintegration of the prepared tablets and acceptable palatability when using sodium stearyl fumarate as a taste masking agent.

Novel in-situ gel for intravesical administration of ketorolac.

The urinary bladder stores urine until the time of urination. Systemic administration of drugs to treat bladder diseases faces several limitations. Therefore, intravesical drug delivery is a promising alternative route of administration. An in-situ gel is used to form a gel inside the bladder cavity and ensure continuous release of the drug even after urination. The objective of the present study was to optimize an in-situ gel formulation of poloxamer and chitosan for intravesical delivery of ketorolac tromethamine. The gelling temperature of the prepared combinations ranged from 20.67 to 25.8 °C. In-vitro release of KT was sustained for up to 7 h using a poloxamer concentration ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%. Design-Expert® 10 was used to select the optimized formulation (poloxamer/chitosan 17/1.589% w/w) which significantly (p < 0.05) extended the drug release more than each polymer alone. An ex-vivo study showed the ability of the optimized formulation to sustain drug release after emptying two times to mimic urination. Furthermore, the formed gel adhered to the bladder tissue throughout the time period of the experiment. Intravesical administration of the optimized formulation to rabbits via catheter showed no obstruction of urine flow and continuous release of the drug for 12 h.

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.