New solid self-microemulsifying systems to enhance dissolution rate of poorly water soluble drugs

Abstract

CONTEXT: An adequate drug dissolution behavior is essential for the therapeutic effectiveness of all solid dosage forms. OBJECTIVE: To develop a new solid self-micro-emulsifying drug delivery system (S-SMEDDS) to improve the dissolution properties of poorly water-soluble drugs, such as glyburide. METHODS: Liquid self-micro-emulsifying drug delivery systems (SMEDDS) consisted of Labrafac-Hydro(®), Tween(®) 20, Transcutol(®), and drug. S-SMEDDS were prepared by adsorption of SMEDDS onto different adsorbents; the obtained powders were evaluated for flow, compactability and liquid-retention potential. The reconstitution ability of S-SMEDDS into SMEDDS by re-dispersion in water was assessed. Tablets, prepared by direct compression of selected S-SMEDDS, were characterized for technological properties and dissolution behavior. RESULTS: Neusilin US2 was selected as the most effective adsorbent, based on its better flow and compacting properties, greater surface area and mesoporosity. The significantly higher (P < 0.001) drug dissolution rate from S-SMEDDS-based tablets than from commercial tablets was ascribed to enhanced wetting and surface area of drug, finely distributed onto the hydrophilic adsorbent, and, above all, to the already drug dissolved form in the SMEDDS system. Properties, drug content and dissolution from S-SMEDDS tablets were unchanged after 25°C and 60% RH six-month storage. CONCLUSIONS: The developed tablets showed the advantages of SMEDDS, allowing a strong improvement of drug dissolution, together with increased physical and chemical stability.