Optimized preparation of in situ forming microparticles for the parenteral delivery of vinpocetine.
ABSTRACT A spherical symmetric design-response surface methodology was applied to optimize the preparation of vinpocetine-loaded poly(D,L-lactide-co-glycolide) PLGA in situ forming microparticles (ISM system). The influence of the ratio of PLGA to vinpocetine (w/w), the concentration of Tween 80 (w/v) and the volume of propylene glycol on the burst release, medium particle diameter and size distribution was evaluated. Scan electron microscopy of the optimized in situ microparticles exhibited spherical shape, and vinpocetine-loading mainly inside the microparticles. The data showed that the release of vinpocetine from in situ microparticles in vitro and in vivo lasted about 40 d. In vivo pharmacokinetic characteristics of the optimized in situ microparticles was assessed after they were intramuscularly injected into rats. HPLC method was used to determine the plasma concentration of vinpocetine. The absolute bioavailability of vinpocetine in the microparticles was 27.6% in rats, which suggested that PLGA in situ microparticles were a valuable system for the delivery of vinpocetine.
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ABSTRACT: Abstract Aim: To study the effect of poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles (MPs) preparation techniques on particle physical characterization with special emphasis on burst drug release. Methods: A basic drug clozapine was used in combination with acid-terminated PLGA. Two approaches for MP preparation were compared; the in situ forming microparticle (ISM) and the emulsion-solvent evaporation (ESE) methods using an experimental design. The MPs obtained were compared according to their physical characterization, burst release and T80%. An in vivo pharmacokinetic study with in vitro-in vivo correlation (IVIVC) was also performed for the selected formula. Results: Both methods were able to sustain drug release for three weeks. ISM produced more porous particles and was not effective as ESE for controlling burst release. A good IVIVC (R(2) = 0.9755) was attained when injecting the selected formula into rats. Conclusion: MPs prepared with ESE showed a minimum burst release and a level A IVIVC was obtained when administered to rats.Journal of Microencapsulation 06/2014; · 1.57 Impact Factor
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ABSTRACT: In situ forming implants (ISI) based on phase separation by solvent exchange represent an attractive alternative to conventional preformed implants and microparticles for parenteral applications. They are indeed easier to manufacture and their administration do not require surgery, therefore improving patient compliance. They consist of polymeric solutions precipitating at the site of injection and thus forming a drug eluting depot. Drug release from ISI is typically divided into three phases: burst during precipitation of the depot, diffusion of drug through the polymeric matrix and finally drug release by system degradation. This review gives a comprehensive overview on (i) the theoretical bases of these three phases, (ii) the parameters influencing them and (iii) the remaining drawbacks which have to be addressed to enlarge their commercial opportunities. Indeed, although some of them are already commercialized, ISI still suffer from limitations: mainly lack of reproducibility in depot shape, burst during solidification and potential toxicity. Nevertheless, depending on the targeted therapeutic application, these shortcomings may be transformed into advantages. As a result, keys are given in order to tailor these formulations in view of the desired application so that ISI could gain further clinical importance in the following years.Journal of Controlled Release 08/2013; · 7.63 Impact Factor