Formulation, In-vitro and Antifungal Activity of Fluconazole by Absorbant Solid Dispersion

Abstract

Fluconazole is a antifungal drug used for numerous systemic and artificial fungal infections. However, it has many boundaries when directed in the form of oral solid dosage forms due to its poor aqueous solubility and dissolution profile, which is a major effort in reaching adequate oral bioavailability. Adsorbent solid dispersion (ASD) is one of the highly promising methods for ameliorating the wettability and solubility of medications having low aqueous solubility. The current research aims to improve the dissolution and solubility profile of fluconazole using the ASD approach. Polyethylene glycol 6000 (PEG 6000), Poloxamer 188 and Poloxamer 407 were applied as water- soluble polymeric carriers to trap the drug in an amorphous state and improve dissolution profile. In addition, Aerosil 200 and Aerosil 300 were utilized as highly porous carriers (adsorbents) to drastically increase the drug's contact area with dissolution media. Six adsorbent solid dispersion formulas (ASDF1 - ASDF6) were prepared using the melting method in a ratio of 0.25:0.25:0.25 (drug: carrier: adsorbent). The prepared mixtures were evaluated for saturated solubility, drug content, percentage yield, in-vitro release and antifungal activity. The prepared formulations showed an improvement in the drug's solubility. The greatest result was achieved with formulation Flu4(Poloxamer407, Aerosil 3000 and Fluconazole), which showed an increase in solubility associated with pure fluconazole. This enhancement is attributed to the alteration of the drug into an amorphous state and the massive surface area providing by the porous carriers.