Pluronic and tetronic copolymers with polyglycolyzed oils as self-emulsifying drug delivery systems.
The potential of poly(ethylene oxide)-poly(propylene oxide) block copolymers Pluronic F127 (PF127) and Tetronic 304 (T304), 904 (T904) and 1307 (T1307) as components of solid self-(micro)emulsifying dosage forms, S(M)EDDS, was evaluated. The dependence of the self-associative properties of Tetronics on pH explained the low ability of the micelles to solubilize griseofulvin at acid pH (sevenfold increase) compared to at alkaline pH (12-fold). Blends of polyglycolyzed glycerides (Labrasol, Labrafac CC, and Labrafil M 1944CS) with each copolymer at two different weight ratios (80:20 and 60:40) were prepared, diluted in water, and characterized in terms of globule size, appearance and griseofulvin solubility. The blends with Labrasol led to microemulsions that are able to increase drug solubility up to 30-fold. SMEDD hard gelatine capsules filled with griseofulvin and Labrasol or Labrasol/copolymer 80:20 showed a remarkable increase in drug solubility and dissolution rate, particularly when T904, T1307 or PF127 was present in the blend. This effect was more remarkable when the volume of the dissolution medium was 200 ml (compared to 900 ml), which can be related to a higher stability of the microemulsion when there is a greater concentration of the copolymer and glyceride in the medium.
Fernandez-Tarrio
Marta
M
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Yañez
Fernando
F
Immesoete
Kristof
K
Alvarez-Lorenzo
Carmen
C
Concheiro
Angel
A
D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005029:Ethylenediamines / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry*; D006118:Griseofulvin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008956:Models, Chemical; D008970:Molecular Weight; D009821:Oils / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
D002214:Capsules; D004337:Drug Carriers; D004655:Emulsions; D005029:Ethylenediamines; D005989:Glycerides; C514708:Labrafil M 1944 CS; D009821:Oils; D009930:Organic Chemicals; D011073:Polyamines; C000610401:Tetronic 1307; C525597:Tetronic 904; C440220:Labrasol; D020442:Poloxamer; D006118:Griseofulvin; D011092:Polyethylene Glycols; D005780:Gelatin