Effects of Formulation Parameters on Encapsulation Efficiency and Release Behavior of Risperidone Poly(D,L-lactide-co-glycolide) Microsphere

College of Life Science, Jilin University, 2699 Qianjin Street, Changchun, China.
Chemical & pharmaceutical bulletin (Impact Factor: 1.16). 11/2009; 57(11):1251-6. DOI: 10.1248/cpb.57.1251
Source: PubMed


A 4-week sustained release risperidone biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microsphere for the therapy of schizophrenia, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The risperidone PLGA microspheres were prepared by O/W solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, GC and HPLC-MS. The results indicated that the morphology of the risperidone PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 32 to 92 microm and the drug encapsulation efficiency was influenced by homogeneous rotation speed, intrinsic viscosity, carboxylic terminal group, the polymer concentration in the oil phase and the molecular weight of the polymer. These changes were also reflected in drug release. When the Mw of the polymers increased from ca. 28000 to ca. 90000, the initial burst release of risperidone PLGA microspheres decreased from 13 to 0.8% and the sustained-release could be extended to 4 weeks. Pharmacokinetic study on beagle dogs showed that the 4-week sustained release profile of the risperidone loaded microspheres prepared with 75253A was verified. The PLGA 75253A and 75255A show the potential as excipients for the monthly sustained release risperidone PLGA microspheres due to higher encapsulation efficiency and almost zero-order release kinetics of release profile.

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    • "Therefore, the incorporation of bases into microspheres may improve the release kinetics of risperidone PLGA microspheres toward a continuous and uniform fashion. Similarly, Su et al. (2009) studied the effects of formulation parameters on encapsulation efficiency and release behavior of risperidone PLGA microspheres. The microspheres were prepared by the O/W solvent evaporation method using PLGA 7525 polymers (lactide:glycolide = 75:25). "
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    ABSTRACT: Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug.
    Full-text · Article · Apr 2013 · Archives of Pharmacal Research
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    • "The feasibility of formulating risperidoneloaded poly(epsilon-caprolactone) nanoparticles for the treatment of psychotic disorders was also evaluated by Singh and Muthu [114] [116] [117]. In contrast to the already commercialized long-acting polymer-based risperidone systems, new polymer-based matrix systems [115] and microparticles [118] [119] [120], were developed as an effort to reduce the number of required administered doses, allowing for a sustained drug release effect. Nonetheless, they are out of the scope of this review. "
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    ABSTRACT: Currently Alzheimer's disease and schizophrenia are both well-established neuropsychiatric diseases. Nonetheless, the treatment of these disorders is not unanimous and fully effective. As a consequence, several approaches have been studied to improve patient's conditions. In this context, the development of new drug nanodelivery systems to increase drug bioavailability and reduce adverse effects has been claimed as a good option. Among these systems we focus on the ones that seem most promising, such as lipid-based systems (e.g. liposomes, nanoemulsions and lipid nanoparticles), drug nanocrystals, polymeric nanoparticles and micelles. Moreover, the application of these systems by means of alternative administration routes is also discussed. Regardless of the satisfactory results and the associated progresses that have been done in the last years, more studies are required to quickly licence the application of drug nanodelivery systems in human medicines.
    Full-text · Article · Mar 2013 · Current pharmaceutical design
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    • "Since it has been reported that blended polymers could better modulate the release profile and reduce the initial burst release of the microspheres (Blanco-Príeto et al., 2004), the present study also aimed to assess two selected mixtures of PLGAs of different molecular weights, 12K (2A) and 47K (3A), and of PLGA2A with polylactic acid (PLA; MW$83K) for these potential formulation advantages. It has been widely reported that the physicochemical properties of encapsulating polymers, notably hydrophobicity and molecular weight, could play a critical role in regulating the drug encapsulation efficiency and in vitro drug release profile for the microspheres (Yeo and Park, 2004; Su et al., 2009). Increasing the molecular weight of the polymer may improve the encapsulation efficiency and reduce the initial burst release of the protein, but may substantially lower the subsequent protein release rate (Yang et al., 2001; Wu et al., 2009), while raising the hydrophobicity may decrease the initial burst release but can cause low encapsulation efficiency and incomplete release (Yeo and Park, 2004; Bertram et al., 2009). "
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    ABSTRACT: This study aimed to assess the potential merits of formulating sustained-release microspheres of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) via freezing-induced phase separation (FIPS) of the protein with dextran followed by encapsulation with binary mixture of poly(lactic-co-glycolic acid) (PLGA) 2A (MW∼12K) and 3A (MW∼47K) or of PLGA2A and polylactic acid (PLA; MW∼83K). The formulated dextran particles and microspheres were characterized in vitro for loading, aggregation, bioactivity and release behavior of the protein where appropriate. rhGM-CSF retained about 60% of bioactivity with no significant aggregation after each formulation step. Encapsulation of protein-loaded dextran particles attained only 80% with the PLGA2A and PLGA3A blend, but 100% with the PLGA2A and PLA mixture. The former formulation exhibited a triphasic in-vitro release profile typical of PLGA microspheres while the latter revealed a much lower initial burst followed by a steady and complete release of rhGM-CSF with preserved bioactivity over a 15-day period.
    Full-text · Article · Oct 2011 · Journal of Microencapsulation
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