In this work, the feasibility to develop micelle carriers of griseofulvin based on PLA-PEG copolymers was investigated. With the use of the dialysis method of micelle formation, the micellization behavior of a range of PLA(X)-PEG(5) copolymers was investigated. At copolymer concentrations in the organic solvent 10-20 mg/mL, stable micelles with 100% yield could only be prepared from PLA(X)-PEG(5) copolymers with molar composition in the range 50-70% PEG. The copolymers exhibited sufficiently low CMC to provide stable micelles in vivo. The loading capacity of PLA(4)-PEG(5) micelles with griseofulvin was 6.5 mg of drug/1 g of copolymer. The release of griseofulvin from the PLA-PEG micelles in vitro in phosphate-buffered saline (PBS) was sustained over 30 days. No burst effect was observed. Analysis of the release kinetics suggested that the release was erosion-controlled. The release profile was biphasic. Micelle degradation data in PBS indicated that the second phase of release was induced by copolymer degradation. The PLA-PEG micelles of griseofulvin were stable in simulated gastric and intestinal fluids for a long-enough time for oral application. Overall, the PLA-PEG micelles have suitable properties to be considered as potential oral or topical formulations of griseofulvin, provided that the drug-loading capacity of the micelles is sufficiently improved.
The effect of sodium alginate on the crystal growth of hydroxyapatite (HAP) was investigated at sustained supersaturation by the constant composition technique. Sodium alginate was found to inhibit HAP crystal growth at low concentrations and reduced the crystal growth rates by 42-86% for inhibitor concentrations of 2.1x10(-7)-12.6x10(-7) mol/l. The inhibition effect on the crystal growth rate may be explained possibly through adsorption onto the active growth sites. A detailed kinetics analysis suggested a Langmuir-type adsorption of the alginate on HAP surface and a value of 1.63x10(7) l/mol was obtained for the affinity constant of sodium alginate for the surface of HAP. The apparent order for the crystallization reaction was determined to be approximately 2, thus suggesting a surface diffusion controlled spiral growth mechanism.
A very sharp crossover is observed in the variation of the reduced viscosity qsp/c as a function of the concentration c for mixtures of 1 : 1 by weight mixtures of polystyrene and poly(methy1 methacrylate) in benzene at 20°C and a 1 : 1 by weight mixture of poly(ethy1ene glycol) and polystyrene in benzene at 20°C. The crossover is attributed to the critical concentration of the two respective polymers in the solution and its sharpness is due to the incompatibility between the two different polymers.
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