The Influence of Particle Size and Dissolution Rate on Bioavailabilty of Two Indomethacine Capsules

Abstract

Indomethacin is a drug of very low aqueous solubility and poor wetability, all characteristics which make it a drug with a potenial bioavailability problem. Thus, the present study was undertaken to estimate the bioavailability of indomethacin capsules, having different particle sizes and dissolution rates. The particle size, dissolution rates and the bioavailabilities of two indomethacin capsules, indomethacin generic capsules DP (Darou Pakhsh Co.) and indocid (Merk sharp & Dohme)were studied. The median indomethacin particle size of indocid MSD and indomethacin capsules DP were found to be 5.23 mm and 8.61 mm respectively. It also has been found that the dissolution rates and rates of absorption (measured as Ka and peak plasma time ) are dependent upon the particle size of indomethacin preparations (i.e.the higher particle size, the slower dissolution and absorption). But the total amount of drug absorbed (measured as AUCinf )is not affected by the particle size. While the plasma concentration time curve after the administration of indocid capsules shows a distinct distribution and elimination phases, this was iess apparent following the administration of indomethacin generic capsules. Therefore, it is concluded that the particle size and rate of dissolution not only affect the peak time and level, but it may also affect the apparent pattern of indomethacin pharmacokinetics.