Controlled release of solid-reversed-micellar-solution (SRMS) suppositories containing metoclopramide-HCl.
The investigated drug delivery system is a solid-reversed-micellar-solution (SRMS). The composition of this solution is 70% Witepsol W35 and 30% (w/w) lecithin. 1% (w/w) metoclopramide-HCl (MCP) was solubilized in the SRMS. After melting and on contact with water or any physicological aqueous media the SRMS exhibits an application induced transformation into a semisolid system of liquid crystalline microstructure. The structure of the liquid crystal has been identified by polarized light microscopy as a lamellar mesophase. Due to a low coefficient of diffusion in this mesophase a controlled release of the drug may be possible. The release profiles of the in vitro experiments have shown zero order kinetics and a sustained release of the SRMS-suppositories (SRMS-supp.) in comparison with commercial suppositories (Gastrosil-supp.). To examine bioavailability an in vivo study with rabbits was carried out. Five SRMS-supp. (10 mg MCP) and five Gastrosil-supp. (10 mg MCP) were tested in a parallel-group study. These experiments have shown a five times longer mean residence time (parameter of sustained release) in comparison with Gastrosil-supp. In vitro and in vivo studies have shown that rectal application of SRMS-supp. provides an appropriate route for controlled release of MCP via application induced transformation into liquid crystals.
Schneeweis
A
A
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstr. 1, 38106, Braunschweig, Germany.
Müller-Goymann
C C
CC
D000285:Administration, Rectal; D000818:Animals; D000932:Antiemetics / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D008787:Metoclopramide / Q000737:chemistry* / Q000493:pharmacokinetics; D008823:Micelles; D011817:Rabbits; D012996:Solutions; D013488:Suppositories
D000932:Antiemetics; D003692:Delayed-Action Preparations; D008823:Micelles; D012996:Solutions; D013488:Suppositories; D008787:Metoclopramide