Title : Increasing the solubility of spironolactone by the solid dispersion method
Abstract:
Spironolactone belongs to the second class of the bio pharmacy classification system (BCS). All of the drugs, which are classified in this group, suffer from the solubility as the major problem. For this reason, application of any different technique which increases the solubility of drug in the gastrointestinal fluid plays the important role in increasing the oral bioavailability of drug. The goal of this study is to increase the solubility of spironolactone by the solid dispersion method. The different formulations were fabricated by dispersing of spironolactone particles in the melted poly ethylene glycol (PEG) with different molecular weight (Mw). The ratio of PEG: drug was varied in different formulations. The release pattern of drug from each formulation was evaluated by the in vitro tests.
The plasma samples were collected 1, 2, 3, 4, 12 and 24 hours after oral prescription of the formulations. The concentration of drug in each plasma sample was measured by the valid HPLC method. The plasma concentration time profiles after oral prescription of formulations were drowning. The most important parameters of the plasma concentration time curves such as AUC, Cmax, and Tmax was calculated. The results of the in vitro tests showed that the solubility of formulation containing polymer: drug ratio (1:01) and (401) was more than the others. Increasing the molecular weight of PEG from 0::: to 2:::: and the ratio of PEG to drug from 401 to 1:01 had not the significant effect on the solubility of drug. The results of the in vivo tests showed that the application of PEG had the significant effect on the rate and the extent of the drug oral absorption.
Keywords: Spironolactone, Solid Dispersion, Solubility, Oral Bioavailability.
