Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS.
In order to gain a better understanding of the reasons of successful self-microemulsifying drug delivery systems (SMEDDS) formulation, ten poorly water-soluble drugs, exhibiting different physicochemical properties, were selected. The solubility of the compounds was determined in various oils (long and medium chain) and surfactants (HLB>12 and HLB<10). The best performing excipients were selected for SMEDDS formulation. The droplet size and zeta potential of SMEDDS were measured in the absence and the presence of drug. Media, time and the presence of drug showed little or no influence on droplet size of most systems. Some systems displayed a different zeta potential in the presence of drugs. In vitro pharmaceutical performance of the SMEDDS formulations was investigated using the dialysis bag method in reverse mode next to conventional in vitro release methodology. The results suggested that the measured concentration of the compounds inside the dialysis bag corresponded to solubility of the compound in the release medium, which suggested that the formation of micelles inside the dialysis bag was delayed or disturbed. Conventional in vitro release methodology with pH change from acidic to neutral appeared as a simple method which gives valuable information about the dispersion and the solubilization ability of the SMEDDS formulation at different pHs. In general, formulate-ability in SMEDDS was found to depend on the solubility of the drugs in the excipients and log P of the compounds (the optimal log P was found between 2 and 4).
Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Belgium.
Thao Do
TD
Thi
Michiel
M
Van Speybroeck
Valery
V
Barillaro
Johan
J
Martens
Pieter
P
Annaert
Patrick
P
Augustijns
Jan
J
Van Humbeeck
Jan
J
Vermant
Guy
G
Van den Mooter
D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D003956:Dialysis / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000639:trends; D045703:Emulsifying Agents / Q000493:pharmacokinetics; D005079:Excipients / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000493:pharmacokinetics; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility
D045703:Emulsifying Agents; D005079:Excipients; D008055:Lipids; D004364:Pharmaceutical Preparations