EFFECT OF COMBINED CARRIERS OF COLLOIDAL SILICON DIOXIDE AND WATER-SOLUBLE POLYMER ON DISSOLUTION AND DENSITY OF FENOFIBRATE FORMULATIONS PREPARED BY MELTING METHOD

Abstract

Fenofibrate (FN), colloidal silicon dioxide (CSD) and water-soluble carriers (PEG4000 or PEG6000) at the ratio of 1:1:1 was prepared by melting method. Dissolution profiles of different types of PEG were similar. PEG4000 was selected to prepare the formulations and order of mixing during melting process on drug release was investigated. Melting FN and CSD before adding PEG4000 gave higher drug dissolution than other type of order of mixing. Poloxamer188 (P188) was also used in comparison with PEG4000. Formulations of PEG4000 (1:1:0.1, 1:1:0.5, 1:1:1) and that of P188 (1:1:0.5, 1:1:0.75, 1:1:1) were prepared to investigate the effect of type and quantity of combined carriers on drug dissolution and granule density. Increasing of combined carriers ratio would markedly increase granule density while decreasing of drug dissolution.  Formulation of FN:CSD:P188 at the ratio of 1:1:0.5 produced high drug release and increased in granule density, therefore, it was selected to prepare the capsules product with and without superdisintegrant (croscarmellose sodium). It was found that capsules containing croscarmellose sodium gave faster disintegration time and higher drug release than that of without disintegrant. The formulation of FN and CSD could be prepared by melting method with P188 as combined carrier for increasing dissolution and granule density.