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Etude des interactions de mélanges (polymères biodégradables/principe actif) obtenus par différentes méthodes de préparations

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par L'hachemi AZOUZ
Université A/Mira-Bejaia - Magister 2010

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Abstract :

This work it puts in the context of the synthesis of a biodegradable polymer derived from renewable resources such as corn, and its application in biomedical area, particularly as drug carriers. Three poly(D,L-lactic acid) polymers with different molecular weights (1000, 3000 and 9000) g/mol were synthesized by a method of azeotropic condensation polymerization of D,L-lactic acid at 140°C under vacuum with using a catalyst (SnCl2). Molecular weights of PDLLAs were determined by a viscosimeter (Ubbelhode).

Thereafter, PDLLA/ibuprofen (IB) mixtures were prepared using three methods of preparation such as physical mixes, hot mixes and solvent evaporation methods. For each mixture, three formulations (F5, F15 et F25) were prepared. All the formulations contain the same quantity of IB (20 mg) but they differ from the quantity of PDLLA loaded 5% (F5), 15% (F15) et 25% (F25).

The crude compounds (PDLLA, IB) as well as the different formulation were characterized by using several characterization physical methods as FTIR, XRD, SEM and DSC. We noted that, once the particles of IB are mixed with those of PDLLA, size and morphology of particles were altered. Moreover, FTIR methods revealed that the absorption band in the region of carbonyl of ibuprofen was shifted towards the higher frequencies (í), once IB is mixed with PDLLA. Indeed, interactions with hydrogen with hydrogen bonding were supposed to be existing between IB and PDLLA. The X-ray diffraction revealed that the spectrum of ibuprofen undergo certain changes such as widening of the width, increase height, and shift of the peaks.

The results of in vitro dissolution showed that the rate release of ibuprofen was modified in all the formulations. Ibuprofen was released in fast way at the first stage, followed by slow release (or quick/slow profile). The rate release of the IB decreases when the quantity and the molecular weights of PDLLA increases. The release kinetics of IB is faster in an alkaline medium of dissolution (pH 7.4) that in an acidic one (pH 5.8). The release kinetics of ibuprofen also slows down according to the method of preparation in the order : hot mix, physical mix and solvent evaporation mix.

Keywords: Poly(D,L-lactic acid) (PDLLA), Ibuprofen, Biodegradable polymers, drug carriers, physical mixes, hot mixes, solvent evaporation methods.

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