Guang-Hui Ma

Preparation of uniform poly(lactide) microspheres by employing the Shirasu Porous Glass (SPG) emulsification technique

Abstract Relatively uniform biodegradable poly(lactide) (PLA) microspheres were prepared by employing a Shirasu Porous Glass (SPG) membrane emulsification technique. Poly(lactide) dissolved in co-surfactant (hydrophobic substance)/dichloromethane (DCM) was used as a dispersed phase (oil phase) and an aqueous phase containing poly(vinyl alcohol) (PVA) and sodium lauryl sulfate (SLS) was used as a continuous phase. The oil phase permeated through the uniform pores of the SPG membrane into the continuous phase by a pressure of nitrogen gas to form the droplets. Then, the solid polymer microspheres were obtained by simply evaporating DCM at room temperature for 24 h. The effects of the type and the amount of the co-surfactant, and PLA concentration on the size, size distribution, and the morphologies of the droplets and particles were investigated. A relatively uniform spherical PLA microsphere was obtained successfully by using lauryl alcohol (LOH) rather than hexadecane (HD) as a co-surfactant. PLA concentration was varied from 10 to 20 wt.%/vol., and the LOH/DCM ratio changed from 0.5:11.5 to 2:10 by volume. At the polymer concentration range used in this study (10–20 wt.%), variation of the droplet size was not so apparent when 2 ml of LOH was used, but the droplet size showed a minimum value at 15 wt.% when 0.5 or 1 ml of LOH was used. The variation of CV value (coefficient of variation) was smaller in the PLA concentration range of 10–15 wt.%, then the CV value became larger as the PLA concentration was increased from 15 to 20 wt.%. Although there was a tendency that the droplet size and the CV value decreased as the LOH/DCM ratio increased, the CV value of the particle after the evaporation of DCM showed the lowest value when the amount of LOH was 1 ml (LOH/DCM=1:11, by vol.). Therefore it was most adequate to use 1 ml of LOH to prepare the particles with a relatively narrow size distribution. Furthermore, it was clarified that the phase-separation between PLA and LOH was apparent and the surface of the particle obtained was wrinkled when the PLA concentration was lower after DCM was evaporated, while the particles with the smooth surface were obtained when the PLA concentration was higher. This method provides a unique technique to prepare uniform polymer microspheres composed of natural polymers, bio-degradable polymers, co-polymers or polymer blends, polyesters and those which can not be polymerized by the radical polymerization.

Preparation and Analysis of Uniform Emulsion Droplets Using SPG Membrane Emulsification Technique

Abstract A new technique for the preparation of uniform emulsion droplets using Shirasu porous glass (SPG) membranes was evaluated. The hydrophobicity of a dispersion phase and the concentration of the mixed surfactant, by which the interfacial tension between the continuous phase and the dispersion phase was changed, significantly affected the droplet size and size distribution. From the point of view that the difference in the interfacial energy affects the characteristics of the droplets, the effect of wettability of the dispersion phase on the thin layer of the continuous phase on the membrane surface was investigated by measuring the contact angle. It is understood that monodispersity of the droplets is controlled by the wettability of the dispersion phase for the continuous phase in contact with the SFG membrane. The droplet profiles at the initial stage and the final release shown in the schematic diagrams corresponded to the value of adhesional work as a scale of the wettability.

Application of Porous Microspheres Prepared by SPG (Shirasu Porous Glass) Emulsification as Immobilizing Carriers of Glucoamylase (GluA)

Fairly uniform spheres of crosslinked polystyrene (PS) and polymethyl methacrylate (PMMA), prepared by a particular emulsification process using SPG (Shirasu Porous Glass) membranes and subsequent suspension polymerization, were applied for immobilizing carriers of Glucoamylase (GluA). A mixture of monomers, solvents, and oil-soluble initiator was allowed to permeate through the micropores of SPG, suspended in an aqueous solution of poly(vinyl alcohol), and polymerized while retaining the narrow size distribution during polymerization. A small amount of acrylic acid or glycidyl methacrylate (GMA) was incorporated for the immobilization of GluA via covalent bonding. Although GluA has been regarded as being difficult to retain its activity after the immobilization process, a porous structure of the carriers definitely favored the immobilization, and a maximum 55% relative activity (RA) was obtained by the physical adsorption to PMMA spheres. The reaction of epoxide in GMA with 6-aminocaproic acid provided a spacer arm for the carboxyl group. An improvement of activity was expected by the incorporation of the spacer arms; however, barely noticeable activity was observed for PMMA carriers either by the physical adsorption or by the covalent bonding. A slight improvement was observed for PS carriers with spacers compared to the carriers without them. The diffusion process of oligosaccharides in the porous carriers seemed to retard the rate of hydrolysis in the case of largest carriers, 60 μm PS-DVB-AA spheres. The activity of immobilized GluA was retained during a long storage period of more than 150 days, some of them even increasing gradually, while the activity of native GluA dropped to zero after 100 days.

Synthesis of uniform microspheres with higher content of 2-hydroxyethyl methacrylate by employing SPG (Shirasu porous glass) emulsification technique followed by swelling process of droplets

Relatively uniform microspheres containing a hydrophilic monomer, 2-hy- droxyethyl methacrylate (HEMA), were prepared by employing a swelling method of uniform seed droplets. A uniform seed emulsion composed mainly of styrene (St) was prepared by the Shirasu porous glass (SPG) membrane emulsification technique; this was mixed with a secondary emulsion composed mainly of HEMA/St or HEMA/MMA (methyl methacrylate) prepared by a homogenizer for swelling. The swollen droplets obtained were polymerized at 757C under a nitrogen atmosphere. The uniform mi- crosphere with a higher content of HEMA was obtained successfully by the swelling method while it failed by a direct emulsification method. The effects of the composition of the oil phase and the inhibitor in the continuous phase on the incorporated fraction of HEMA, the morphology of particles, and monomer conversion were investigated. It was found that the incorporated fraction of HEMA increased with increasing its feed fraction, and more HEMA was incorporated into the microsphere when HEMA/MMA was used as the oil phase of the secondary emulsion rather than HEMA/St. Although the final conversion was very low when the feed fraction of HEMA was higher, it can be increased to more than 80% by using an adequate amount of ethylene glycol dimethacrylate (EGDMA) as a crosslinker and NaNO2 as an inhibitor in the aqueous phase. Various microspheres with different morphologies such as spherical, snow- manlike, and popcornlike were observed, depending on composition of the oil phase. Furthermore, the porous microsphere with a high content of HEMA was obtained by employing hexanol (HA) as a porogen. q 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1325-1341, 1997

Synthesis of 100 μm uniform porous spheres by SPG emulsification with subsequent swelling of the droplets

mm porous p(styrene-co-divinylbenzene) (PS-DVB) microspheres were synthesized by employing a particular membrane emulsification technique, and subse- quent swelling of the seed droplets. DVB dissolving a water-insoluble substance, hexa- decane (HD), and an initiator was permeated through a SPG (Shirasu porous glass) membrane, and the uniform (seed) droplets were released to a stabilizer solution acting as the continuous phase. The average droplet size was around 30 mm, and this emulsion was mixed with a secondary emulsion of much smaller size consisting of more hydro- philic components, a mixture of styrene, middle chain alcohol (C6 to C8), dichloroben- zene, and isoamyl acetate, which promotes the degradative diffusion process of the components. After all the droplets in the secondary emulsion virtually disappeared, the seed droplets were swollen to a maximum 110 mm. Polymerization was carried out at 348 K under a nitrogen atmosphere. Uniform porous spheres of 100 mm with the coefficient of variation less than 10% were obtained. Specific surface area was 350 m 2 / g. Careful controlling of the specific gravity of swollen droplets and the choice of solvents balancing between the good solvency for the polymer and polarity (solubility in water) proved vital in order that the polymerization may proceed without an extensive phase separation in the early stage, which eventually induces breakup of the droplets. The three component system, isoamyl acetate-hexanol-o-dichlorobenzene, provided an ade- quate cosolvent for these purposes. q 1997 John Wiley & Sons, Inc. J Appl Polym Sci 63: 931-942, 1997

Study on preparation of monodispersed poly(styrene-co-N-dimethylaminoethyl methacrylate) composite microspheres by SPG (Shirasu Porous Glass) emulsification technique

Monodispersed poly(styrene-co-N-dimethylaminoethyl methacrylate) [P(St-DMAEMA)] composite microspheres were prepared by employing a Shirasu Porous Glass (SPG) emulsification technique. A mixture of monomer, hexadecane (HD), and initiator N,N′-azobis(2,4-dimethylvaleronitrile) (ADVN) was used as a dispersed phase and an aqueous phase containing stabilizer [poly(vinyl pyrrolidone) (PVP) or poly(vinyl alcohol) (PVA)], sodium lauryl sulfate (SLS), and water-soluble inhibitor [hydroquinone (HQ), diaminophenylene (DAP), or sodium nitrite (NaNO2)], was used as a continuous phase. The dispersed phase was permeated through the uniform pores of SPG membrane into the continuous phase by a gas pressure to form the uniform droplets. Then, the droplets were polymerized at 70°C. The effects of inhibitor, stabilizer, ADVN, and DMAEMA on the secondary nucleation, DMAEMA fraction in the polymer, conversion, and morphologies of the particles were investigated. It was found that the secondary nucleation was prevented effectively in the presence of HQ or DAP when PVP was used as the stabilizer. The secondary particle was observed when ADVN amount was raised to 0.3 g (/18 g monomer); however, no secondary nucleation occurred even by increasing DMAEMA fraction to 10 wt %. This result implied that the diffusion of ADVN into the aqueous phase was a main factor responsible to the secondary nucleation more than that of DMAEMA. The hollow particles were obtained when NaNO2 was used, while one-hole particles formed in the other cases. By adding crosslinking agent, the hole disappeared and the monomer conversion was improved.

Preparation of polyurethaneurea (PUU) uniform spheres by SPG membrane emulsification technique

Uniform polyurethaneurea (PUU) spheres were prepared from 20–40 wt % urethane prepolymer (UP) solution of xylene. Uniform droplets were formed with the Shirasu porous glass (SPG) membranes of 1.42, 5.25, and 9.5 μm pore size, dispersed in an aqueous phase with dissolved stabilizers, and allowed to stand for the chain extension at the room temperature with diamines that were added after the emulsification. The reaction progressed rapidly by an addition of ethyl acetate to the aqueous phase, promoting the diffusion of diamines into the droplets. The reaction of —NCO groups with water did not hamper the emulsification process, which normally occurred in 1 to 2 h, yielding stable droplets with the coefficient of variation around 10%. No instability or coagulation occurred, while standing for the chain extension, and solid, spherical PUU particles of 5–20 μm were obtained after removal of the solvent.

Synthesis of monodisperse polymeric microspheres including polyimide prepolymer by using SPG emulsification technique

Abstract An occlusion of a functional material, polyimide prepolymer (PIP), into uniform polymeric microspheres was attempted in order to demonstrate the versatility of the SPG (Shirasu porous glass) membrane emulsification technique. An oil phase consisting of hydrophobic monomers (styrene and acrylates with a longer side chain) and, although not necessarily, a water-insoluble reagent (lauryl alcohol) dissolved PIP up to 50 wt.%, and also an initiator (ADVN). An aqueous phase contained polyvinyl alcohol (PVA) and a small amount of sodium lauryl sulfate (SLS) as a stabilizing pair. The former was permeated through a SPG membrane, and uniform droplets were suspended in the latter. The seed droplets were swollen with the hydrophilic components, MMA and EGDMA, with a selective addition of isoamyl acetate, hexanol or octanol. After the swelling, an additional amount of the stabilizer solution was added. Polymerization was carried out at 343 K for 24 h. Uniform polymeric spheres, the coefficient of variation approximately 10% and occluding a maximum 28.4 wt.% of PIP were obtained. The entrapment of PIP was improved when the matrix polymer chains were crosslinked with EGDMA (but not with DVB), and an employment of the acrylates with a longer side chain, implying that the presence of ester groups are favored for a stable occlusion. A co-monomer system composed of MMA, 2-ethylhexyl acrylate and butyl acrylate plus octyl alcohol was able to occlude almost 100% of PIP in a stable condition without the presence of EGDMA.

A Comparison of Membrane Emulsification Obtained Using SPG (Shirasu Porous Glass) and PTFE [Poly(Tetrafluoroethylene)] Membranes

ABSTRACT SPG (Shirasu porous glass) membrane emulsification used to prepare uniform polymeric microspheres is briefly reviewed, and the performance of a hydrophilically treated PTFE [poly(tetrafluoroethylerie)] membrane is described and compared with that of the SPG membrane. A mixture of styrene. divinyl benzene and hexadecane (HD) was extruded through the membranes and dispersed in an aqueous phase containing polyvinylalcohol (PVA) and sodium lauryl sulfate (SLS) as mixed stabilizers. A hvdrophilically treated PTFE membrane was used with a stainless steel mesh support so that the membrane would not expand to affect the pore size during the emulsification. The nominal pore size of the PTFE membrane was replaced with the calculated one using a theoretical expression derived from the force balance between the external pressure and the interfacial tension between oil and water phases. The emulsion droplets prepared with the PTFE membrane revealed a broader size distribution than those obtained with the SPG membrane, and the rate of emulsificaton was nearly same for both membranes. Droplet size control was readily possible. The performance was significantly affected by the adsorption behavior of the stabilizers on the membrane surfaces. The contact angle profile of oil droplets on the PTFE membrane implied that the hydrophilically treated PTFE membrane is still hydrophobic compared to the SPG membrane. This tendency was reflected by the dependence of the average droplet diameter (and coefficient of variation, CV) on the concentration and composition of mixed stabilizers.

Mechanism of suspension polymerization of uniform monomer droplets prepared by glass membrane (Shirasu Porous Glass) emulsification technique

The mechanism of the unique suspension polymerization of uniform monomer droplets, without coalescence and breakup during the polymerization, was investigated using styrene (S) as a monomer mixed with water-insoluble hexadecane (HD). The glass membrane (Shirasu Porous Glass, SPG) emulsification technique was employed for the preparation of uniform droplets. Depending on the pore sizes of the SPG membranes (1.0, 1.4, and 2.9 μm), polymer particles of an average diameter ranging from 5.6 to 20.9 μm were obtained with the coefficient of variation (CV) being close to 10%. The role of HD was to prevent the degradation of the droplets by the molecular diffusion process. Sodium nitrite was added in the aqueous phase to kill the radicals desorbed from the droplets (polymer particles), thereby suppressing the secondary nucleation of smaller particles. Each droplet behaved as an isolated locus of polymerization. With the presence of HD, the initial polymerization rate was proportional to 0.24th power of the benzoil peroxide (BPO) concentration. This peculiar behavior as compared with the ordinary suspension polymerization was explained by introducing the assumption that each droplet was composed of isolated compartments (cells) in which active polymeric radicals were dissolved in an S-rich phase and surrounded by a rather incompatible S/HD (continuous) phase. The average number of radicals in the droplet increased initially due to the separate existence of polymeric radicals in compartments. As the polymerization progressed, the HD-rich phase gradually separated, eventually forming macrodomains, which were visible by an optical microscope. The phase separation allowed polystyrene chains to dissolve in a more favorable S phase, and the homogeneous bulk polymerization kinetics took over, resulting in a gradual decrease of the average number of radicals in the droplet until the increase of viscosity induced the gel effect. When no HD was present in the droplets, the polymerization proceeded in accordance with the bulk mechanism except for the initial retardation by the entry of inhibiting radicals generated from sodium nitrite in the aqueous phase.