• 대한의생명과학회지
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• 제12권3호
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• pp.177-183
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• 2006

To demonstrate the effect of formulation conditions and evaluations of structural integrity from ovalbumin containing poly lactide glycolide copolymer (PLGA) microspheres for Vaccine delivery, OVA microspheres were prepared by a W/O/W multiple emulsion solvent extraction technique. Dichloromethan (DCM) and Ethyl acetate (EA) were applied as an organic phase and poly vinyl alcohol (PVA) as a secondary emulsion stabilizer. Microspheres were characterized for particle size, morphology (optical microscopy and Scanning Electron Microscope (SEM)). Protein denaturation was evaluated by size exclusion chromatography (SEC), SDS-PAGE and isoelectric focusing (IEF). Residual organic solvent was estimated by gas chromatography (GC) and differential scanning calorimetry (DSC). Optical photomicrograph and SEM revealed that micro spheres were typically spherical but various morphologies were observed. Mean particle size $(d_{vs})$ of microspheres were in the range of $3{\sim}50{\mu}m$. Also, The protein stability was not affected by the fonnulation process and residual organic solvent was beyond the detection below 0.1ppm. These results demonstrated that micro spheres might be a good candidate for the parenteral vaccine delivery system.

• Journal of Pharmaceutical Investigation
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• 제36권4호
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• pp.245-251
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• 2006

The novel microsphere blending and multiple emulsion method by single process was tried to prepare sustained release microspheres which release a physiologically active substance for long periods of time. A drug was separately dissolved in each of two or more oils containing biodegradable polymers to give the primary oil phases. The primary oil phases were dispersed in single aqueous phase in succession. From the drug-dispersed solution, the organic solvent was removed to produce microspheres. The accelerated drug release from the microsphere formulation prepared by single process through the multiple emulsion method was very similar to a physical blending of separately prepared microspheres using the same polymers. But long term release was not same. In this study, leuprorelin acetate loaded poly(lactide-co-glycolide) microsphere formulation for one-month delivery was developed by the multi-emulsion method followed by solvent extraction/evaporation method.

• Fibers and Polymers
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• 제7권3호
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• pp.229-234
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• 2006

Poly(vinyl acetate) (PVAc)/poly(vinyl alcohol) (PVA)/montmorillonite (MMT) clay nanocomposite microspheres with a core/shell structure have been developed via a suspension polymerization approach. In order to prepare the PVAc/ MMT and PVAc/PVA/MMT nanocomposite microspheres, which are promising precursor of PVA/MMT nanocomposite microspheres, suspension polymerization of vinyl acetate with organophilic MMT and heterogeneous saponification were conducted. A quaternary ammonium salt, cetyltrimethylammonium bromide, was mixed with the MMT in the monomer phase prior to the suspension polymerization. The rate of conversion decreased with an increase in MMT concentration. The incorporation of MMT into the PVAc was verified by FT-IR spectroscopy. Organic vinyl acetate monomers were intercalated into the interlayer regions of organophilic clay hosts and followed by suspension polymerization. Partially saponified PVA/MMT nanocomposite microspheres with a core/shell structure were successfully prepared by heterogeneous saponification.

• Macromolecular Research
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• 제12권5호
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• pp.519-527
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• 2004

Stable poly(methyl methacrylate-co-divinylbenzene) (poly(MMA-co-DVB)) microspheres were prepared by precipitation polymerization using acetonitrile as the main medium under various polymerization conditions, including modifications of the agitation speed, monomer and initiator concentrations, DVB content in the monomer mixture, and the use of various cosolvents. Gentle agitation was required to obtain smooth spherical particles. The individually stable microspheres were obtained at monomer concentrations of up to 15 vol% in an acetonitrile medium. The number-average diameter increased linearly with respect to increases in the monomer and initiator concentrations. We found, however, that the uniformity of the microspheres was independent of the variation of the polymerization ingredients because nuclei formation was solely influenced by the crosslinking reaction of the monomers. We obtained higher yields for the polymerization at higher concentrations of monomer and initiator. The concentration of DVB in the monomer mixture composition played an important role in determining not only the size of the microspheres but also the yield of the polymerization. In addition, although we employed various cosolvents as the polymerization medium, we found that acetonitrile/2-methoxyethanol was the only system that provided spherical particles without coagulation. This finding indicates that the precipitation polymerization is strongly dependent on the solvent used as the medium.

• Journal of Pharmaceutical Investigation
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• 제29권4호
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• pp.315-321
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• 1999

Poly (lactide-co-glycolide) (PLGA) microspheres containing ovalbumin (OVA) as a model protein drug were prepared by double emulsification method, and various conditions such as mixing rate, volume of outer phase and isopropyl alcohol concentration in outer phase during secondary emulsification were observed to control the size of microspheres. In addition, entrapment efficiency of OVA and protein denaturation were also evaluated. As the rate of stirring was increased, the size of particles was decreased. But excessive stirring increased the particle size of microspheres. In a preparation condition of small volume of outer phase, the particle size was decreased but the entrapment efficiency was increased. Adding isopropyl alcohol to outer phase decreased the size of particles, but increased the entrapment efficiency. Microparticles should have smaller size than $10\;{\mu}m$ to be uptaked by Peyer's patch in small intestine. High speed of mixing and relatively small volume of outer phase are needed to reduce the size. In addition, appropriate amount of isopropyl alcohol in outer phase also plays an important role in size reduction of PLGA microspheres.

• Macromolecular Research
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• 제8권2호
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• pp.80-88
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• 2000

Biodegradable microspheres were prepared with poly(L-lactide-co-glycolide) (PLGA, 75 : 25 by mole ratio) by an oil/oil solvent evaporation method for the sustained release of anti-AIDS virus agent, AZT The microspheres of relatively narrow size distribution (7.6$\pm$ 3.8 ㎛) were obtained by controlling the fabrication conditions. The shape of microspheres prepared was smooth and spherical. The efficiency of AZT loading into the PLGA microsphere was over 93% compared to that below 15% for microspheres by a conventional water/oil/water method. The effects of Preparation conditions on the morphology and in vitro AZT release pattern were investigated. in vitro release studies showed that different release pattern and release rates could be achieved by simply modifying factors in the fabrication conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and so on. PLCA microspheres prepared by 5% of initial drug loading, 1.0% (w/w) of surfactant concentration, and 25$\^{C}$ of solvent evaporation temperature were free from initial burst effect and a near-zero order sustained release was observed. Possible mechanisms of the near-zero order sustained release for our system have been proposed.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.408.2-409
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• 2002

The aim of this study is to prepare biodegradable microspheres without use of any kind of surfactants or emulsifiers for a novel sustained delivery carriers of protein drugs. Poly(e-caprolactone)/poly(ethylene glycol)/poly(e-caprolactone) (CEC) triblock copolymer was synthesized by ring-opening of e-caprolactone with dihydroxy poly(ethylene glycol) and was used to make surfactant-free microspheres. (omitted)

• 약학회지
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• 제32권6호
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• pp.371-376
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• 1988

The effect of polysorbate 40, used as a surfactant during the process of manufacture, on the properties of cytarabine microspheres with carnaubu wax was studied. It was revealed that the mean particle size increased in proportion to the concentration of polysorbate 40, and that the dissolution rate of the cytarabine from the microspheres decreased greatly more than the cytarabine powder only, but increased in proportion to the concentration of polysorbate 40 as surfactant.

• Bulletin of the Korean Chemical Society
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• 제34권6호
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• pp.1839-1844
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• 2013

Molecularly imprinted microsphere for chloramphenicol (CAP) with high adsorption capacity and excellent selectivity is prepared by aqueous suspension polymerization, in which chloramphenicol is used as template molecule and ethyl acetate as porogen. The CAP-imprinted microspheres are used as high performance liquid chromatography (HPLC) stationary phase and packed into stainless steel column ($150mm{\times}4.6mm$ i.d.) for selective separation of chloramphenicol. HPLC analysis suggests that chloramphenicol can be distinguished from not only its structural analogs but also other broad-spectrum antibiotic such as erythromycin and tetracycline. In addition, the binding experiments of CAP-imprinted microspheres are carried out in ethanol/water (1:4, V:V), the results indicate that the maximum apparent static binding capacity of molecularly imprinted microspheres is up to 66.64 mg $g^{-1}$ according to scatchard model.

• Macromolecular Research
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• 제12권2호
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• pp.240-245
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• 2004

Monodisperse PMMA micro spheres are prepared by means of a simple soap-free emulsion polymerization in methanol-enriched aqueous medium in a single step process. The size and uniformity of the microspheres are dependent on the polymerization temperature. In a stable system, the uniformity is improved with the polymerization time. The most uniform and stable micro spheres are obtained under mild agitation speed of 100 rpm at 70$^{\circ}C$. The monodisperse PMMA microspheres in the size range of 1.4-2.0 $\mu\textrm{m}$ having less than 5% size variation are successfully achieved with varying concentrations of monomer and initiator. As the monomer and initiator concentrations increase, the larger micro spheres with enhanced uniformity are obtained. However, the decreased amount of water induces the polydisperse PMMA particles due to the generation of secondary particles.