Beck, Ruy Carlos Ruver

Dimer, Frantiescoli Anversa

Guterres, Silvia Stanisçuaski

Pohlmann, Adriana Raffin

English

Lume 5.8

caderno d•farmácla ISSN 0102-6593 Órgão Oficial da Faculdade de Farmácia da Universidade Federal do Rio Grande do Sul volume 26, Suplemento, 201 O J. TECNOLOGIA FARMACÊUTICA E BIOFARMÁCIA 210 ______________ ~:}_L'~~O~~=-~=-(_~------------~P~ha=r~m~ac~e~u=tic=a~lt=ec=h~n~ol~og~y~a~n~d~b~io~ph~a~rm~a~c~y DEVELOPMENT OF OLANZAPINE-LOADED BIODEGRADABLE NANOPARTICLES IN THERMO-SENSITIVE HYDROGEL Dimer F.A.1·, Beck R.C.R. 1, Pohlmann A. R.2, Guterres S. S.1 1Laboratório 405, Faculdade de Farmácia, UFRGS; 2 Laboratório K204, Instituto de Química, UFRGS; *Doutorando - Início: 2009/2 lntroduction: Administration of drug in situ assisted by injectable thermo-sensitive hydrogel, such as Pluronic F127 which exhibit reversible thermal gelation in aqueous solution at concentrations > 15% (w/v), have been an interesting route of administration. Unfortunately, when hydrophobic drugs are considered to be locally delivered by thermo-sensitive hydrogels, their poor solubility make it not well dispersible in the aqueous solution. To overcome the water-soluble problem of hydrophobic drug, biodegradable polymeric nanocapsules were widely studied as drug delivery system. They are a useful tool to encapsulate drug in polymeric nanocapsules to obtain well-dispersed drug to improve its aqueous solubility. Olanzapine, atypical antipsychotic, is a drug used for treatment of schizophrenia and acute manic episodes associated with bipolar disorder. Objective: Create a novel nanocapsule formulation incorporated in a thermo-sensitive hydrogel composite for the administration of a hydrophobic drug such as olanzapine. Materiais and Methods: Lipid-core nanocapsules were prepared by the interfacial deposition of preformed polymer method. Poly(E-caprolactone)(Mw=65.000), caprylic/capric triglyceride, olanzapine and Lipoid S-75® were dissolved in acetone (27ml) at 42ºC. This phase was injected into 53ml of an aqueous phase containing polysorbate 80 under magnetic stirring at room temperatura. After 1 Omin, the suspension was concentrated under reduced pressure to 1 Oml. The particle size, polydispersity index and zeta potential were determined at 25ºC using Zetasizer®. The thermo-sensitive hydrogel (Piuronic F12~ was dispersed in the drug-loaded nanocaJ)sules at 52C and maintained for 24 hours at 5ºC. As a control, a hydrogel containing Pluronic F12"f'> without nanocapsules were also prepared. The total concentration of F127 was maintained between 15% and 22% (w/w). To determine the sol-gel transition behavior, 2.0ml of F12~ solution in water or the nanocapsule suspension was transferred to a test tube and put in a water-bath with temperatura raising from 5ºC to 60"C at a rate of 0.5ºC/min. Olanzapine-loaded nanocapsules prepared and the respectiva hydrogel containing 18% of Pluronic F12~ was evaluated by a Turbiscan Lab at 20"C (suspension and hydrogel) or at 37 ºC (hydrogel) using the scan mode. Results and Discussion: Olanzapine-loaded nanocapsules presented macroscopic homogeneous aspect like milky yellowish opalescent liquids. After preparation, analysis by photon correlation spectroscopy showed a mean particle size of 157nm and low polydispersity index (0.07). lts potential zeta was negative (-23.9mV) indicating stable suspensions. The thermo-sensitive hydrogels with concentrations below 18% did not gel up to 60ºC. On the other hand, concentrations above 18% promete the formation of the hydrogel. The hydrogel containing the nanocapsules showed a lower sol-gel transition temperatura compared to the aqueous dispersion. The injectable gel must have a suitable gelation temperatura (30-36ºC) to be a liquid at room temperatura and to forma gel phase instantly in the body. Hydrogels prepared with Pluronic F127® at 18%, with a gelation temperatura of 31 ºC, were chosen for the next characterization step. The relativa physical stability of olanzapine-loaded nanocapsules and the respectiva hydrogel containing Pluronic F127® at 18% was evaluated by multiple light scattering analyses. The transmittance signal was nu li for ali samples, from t = O to t = 1 h, indicating that backscattering profiles (BS) can be considered for their characterization. Variation of the backscattering signal was below 1% in the middle of the cell for ali formulations indicating that no aggregation or coalescence of the droplets occurred. In addition, only variation of the backscattering signallower than 2.5% at the bottom and at the top of the cuvette were observed, showing that no significant sedimentation and clarification occurred, respectively, even if the hydrogel was analyzed at 37"C. These results demonstrate the physical stability of the formulations. Conclusions: Olanzapine-loaded lipid-core biodegradable nanocapsules were successfully prepared using Pluronic F12~ at 18% promoted the formation of a thermo-sensitive hydrogel suitable to be used as an injectable depot. The developed formulation presents high potential to be used as an intramuscular drug delivery system for hydrophobic drugs as olanzapine. 

Development of olanzapine-loaded biodegradable nanoparticles in thermo-sensitive hydrogel

https://lume.ufrgs.br/bitstream/10183/267758/1/000770362.pdf

Development of olanzapine-loaded biodegradable nanoparticles in thermo-sensitive hydrogel

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Lume 5.8