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.

Tetronic micellization, gelation and drug solubilization: Influence of pH and ionic strength.

The aim of this work was to gain an insight into the self-associative processes and drug solubilization ability of a Tetronic variety, T904 (4 x 15 EO units; 4 x 17 PO units; HLB 15), in aqueous media covering the physiological range of pH and ionic strength, applying isoperibol microcalorimetry, transmission electronic microscopy (TEM), dynamic light scattering (DLS), oscillatory rheometry, and drug diffusion experiments. T904 shows two pK(a) (pK(a1)=4.0 and pK(a2)=7.9) and, at pH<5.8, the diprotonated form predominates over the non-protonated one. Deprotonization of the central diamine group is a required condition for micellization, which is an endothermic entropy-driven process owing to hydrophobic interactions between the PPO chains. As the pH of the solutions decreases, the coulombic repulsions among the positively charged amine groups make the aggregation more difficult, raising the critical micellar concentration (CMC) and decreasing the size of the micelles. The changes in the conformation and hydrophilicity of the Tetronic were reflected in its gelation temperature (around 30 degrees C at neutral-alkaline pH; no gelation at pH<2) and solubilization capacity for griseofulvin (2-fold greater at neutral-alkaline pH than at pH<2) and rate of diffusion (slower at pH 7.4). Such alterations in self-assembly are relevant when using Tetronic in the design of drug delivery systems.