EFFECT OF SUPERDISINTGRANTS AND SOLUBILIZERS ON THE DISSOLUTION RATE AND DISSOLUTION EFFICIENCY OF RITONAVIR TABLETS

Abstract

Ritonavir, a widely prescribed anti-retroviral drug, belongs to Class II under 'BCS' and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Ritonavir is practically insoluble in water and aqueous fluids. Its aqueous solubility was reported to be 2.56 mg/100 ml. As such oral absorption of ritonavir is dissolution rate limited and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. In the case of poorly soluble drugs formulation variables greatly influence their dissolution rate and bioavailability from solid dosage forms. The objective of the present work is to study the effect of five superdisintegrants and three solubilizers on the tablet qualities and dissolution rate of ritonavir tablets to optimize the formulation of ritonavir tablets. Compressed tablets each containing 100 mg of ritonavir were prepared by conventional wet granulation method using five superdisintegrants namely Prosolve, modified starch, croscarmellose sodium, Primogel, crospovidone and three solubilizers namely Tween 80, SLS and PEG 600 and the tablets were evaluated for content of active ingredient, hardness, friability, disintegration time, dissolution rate and dissolution efficiency. The superdisintegrant and solubilizer used has significant influence on the tablet qualities and dissolution rate of ritonavir from the tablets. The order of performance of the superdisintegrants based on increasing dissolution rate was Prosolve > modified starch > croscarmellose sodium > Primogel > crospovidone. Tablets formulated with Prosolve, modified starch and croscarmellose sodium exhibited higher dissolution rates and dissolution efficiency values fulfilling all other official (I.P) and GMP requirements of compressed tablets. Prosolve, modified starch and croscarmellose sodium were found to be better superdisintegrants for ritonavir tablets. The dissolution rate and dissolution efficiency of ritonavir tablets could be significantly enhanced by incorporating the solubilizers (Tween 80, PEG - 600 and SLS) in the tablets. The order of increasing dissolution rate observed with various solubilizers was Tween 80 > PEG - 600> SLS. The dissolution rate and efficiency of ritonavir from tablets could be enhanced by incorporating solubilizers in the tablets