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.Uniterms: Clopidogrel/orally disintegrating tablets. Superdisintegrants. Orally disintegrating tablets/ formulation. Orally disintegrating tablets/evaluation.Recentes avanços em sistemas de liberação de fármacos novos visam à obtenção de melhor adesão do paciente. Um destes avanços é a formulação de comprimidos de desintegração oral (ODTs), que se dissolvem instantaneamente, liberando o fármaco, em alguns segundos, sem a necessidade de água. O principal objetivo deste trabalho foi preparar e desenvolver ODTs de clopidogrel. Os ODTs foram preparados pelo método de compressão direta. Estudou-se o efeito de várias concentrações de diferentes agentes de desintegração, tais como super-crospovidona, croscarmelose de sódio, glicolato de amido de sódio no tempo de desintegração e velocidade de dissolução. Os comprimidos preparados foram avaliados quanto à dureza, à friabilidade, ao tempo de desintegração e à liberação do fármaco in vitro. Além disso, estudou-se a interação de clopidogrel com os excipientes de formulação, utilizando calorimetria de varredura diferencial (DSC). Estudos de DSC revelaram não haver interação entre o fármaco e os excipientes utilizados. Todos os comprimidos possuíam dureza na faixa de 4,0-5,2 kp e a friabilidade inferior a 1%. A variação de peso e o teor de fármaco de todas as formulações mostraram-se dentro do limite oficial, de acordo com a BP. O estudo de liberação do fármaco in vitro de comprimidos ODTs mostrou que mais de 90% do fármaco foram liberados em10 minutos. O teste de palatabilidade em voluntários humanos mostrou sabor e sensação na boca aceitáveis. Assim,...

Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent—Meclizine HCl

“…This may be due to the conversion of the hydrochloride salt to its less soluble free base [15]. Similar pH dependent Meclizine HCl release was also observed by Mahrous et al [2]. …”

“…It is also indicated for pruritus, anaphylactic reactions and vertigo associated with diseases affecting the vestibular system (e.g., Meniere disease, labyrinthitis) [1, 2]. It is more frequently prescribed because of fewer adverse effects [1].…”

“…Literature survey results show that lipid based ER pellets of Meclizine HCl have not been reported yet. Meclizine HCl has a plasma elimination half-life of 5–6 h [1, 2]. For the treatment of vertigo, the standard dose is 25–100 mg/day, given in two or more divided doses [4].…”

Propafenone HCl fast dissolving tablets containing subliming agent prepared by direct compression method

“…The disintegration time was determined in phosphate buffer pH 6.8 using tablet disintegration test apparatus (Electrolab, ED-21, Mumbai, India) on six tablets according to the USP30-NF25 requirements for immediate release tablets. The tablet was put in 500 ml phosphate buffer pH 6.8 and the time taken for the tablet to disintegrate into fine particles was calculated (Mahrous et al, 2016).…”

Untitled

“…Mahrous et al, studied the effect of three superdisintegrants; crospovidone, croscarmellose sodium, and sodium starch glycolate using ODTs of Clopidrogel, they reported that in-vitro disintegration tests and in vitro drug release, tablets showed a fast disintegration within seconds at pH 6.8 and more than 90% of the drug was released within 5 min in acidic medium 18 . Results obtained for the similarity factor at 6 h of release revealed differences in the release profile of the assayed formulations compared to the reference product Table 4.…”