Machanisms of increasing dissolution of indomethacin solid dispersion and corresponding capsules prepared by various amount and types of carriers

Abstract

This study is to elucidate the ability and mechanisms of enhancing dissolution of indomethacin (IDM). The systems, prepared by solvent solid dispersion technique with various amount and four types of carriers, mannitol, PEG 4000, PVP K 30 and sodium lauryl sulfate (SLS), compared with physical mixture systems. The dissolution of capsule containing the prepared systems was also studied. Of four systems, solid dispersion systems showed the greatest dissolution, followed by physical mixture systems, treated IDM and untreated IDM respectively. Amount four types of carriers, PEG 4000, PVP K 30 and SLS seemed to produce the same dissolution of IDM but still more than mannitol. Increasing the amount of carriers increased the dissolution in all systems of all carriers except IDM-SLS physical mixture that exhibited the reversed effect. The dissolution of drug from capsule was better than the corresponding powder. IDM-SLS coprecipitate in capsule showed the fastest time for dissolving 80% of drug. Scanning Electron photomicrograph showed that size reduction, deaggregation with deagglomeration appeared in all IDM-carrier solid dispersions and both IDM-PVP K 30, IDM PEG 4000 physical mixture when compared to untreated drug. Moreover, microenvironmental changing seemed to be occurred in IDM-PVP K 30, IDM-PEG 4000 solid dispersion. Differential thermal analysis thermograms; Infrared spectra and X-ray diffractograms revealed that IDM polymorph was changed from Form I to Form II in all solid dispersion as in treated drug, except IDM-PVP K 30 solid dispersion which showed an amorphous form. Complex formation was also appeared in IDM-PVP K 30 and higher ratio of IDM-SLS solid dispersion. Liquid penetration studies demonstrated that wettability increased in both solid dispersion and physical mixture. Increasing the amount of carriers affected some degree of mechanisms especially particle size reduction, deaggregation and deagglomeration and wettability.