New solid self-microemulsifying systems to enhance dissolution rate of poorly water soluble drugs.
BACKGROUND
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.
Department of Pharmaceutical Sciences, University of Florence, Firenze, Italy. paola.mura@unifi.it
Paola
P
Mura
Maurizio
M
Valleri
Marzia
M
Cirri
Natascia
N
Mennini
D017607:Aluminum Compounds; D000538:Aluminum Silicates / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005905:Glyburide / Q000008:administration & dosage / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D017616:Magnesium Compounds; D016062:Porosity; D011208:Powders; D017640:Silicates; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D014867:Water / Q000737:chemistry
D017607:Aluminum Compounds; D000538:Aluminum Silicates; D004655:Emulsions; D005079:Excipients; D017616:Magnesium Compounds; D011208:Powders; D017640:Silicates; D013607:Tablets; D014867:Water; C033065:aluminum magnesium silicate; D008274:Magnesium; D005905:Glyburide