Microspheres prepared with

The present paper reports on a study which was conducted to investigate the effect of NaOH on the in vitro release profiles of microspheres prepared with polylactides (2) Since these polyesters degrade by hydrolysis (4), it is possible that the molecular weight of the polymers can be decreased by the alkaline pH of the sodium oleate emulsifier solution (pH 10) during fabrication. This in turn could affect the release kinetics of the microspheres. 

The effect of NaOH on drug release was examined with microspheres prepared with thioridazine and two biodegradable polymers. The wall-forming polymers were poly(DL-lactide) and poly(L-lactide). Sodium oleate was used as the emulsifier, with the exception of one set of experiments where the emulsions were stabilized with polyvinyl alcohol. 

The release profile of a batch of microspheres prepared with NaOH-pretreated polymer is shown in Figure 5. For comparison, release curves for microspheres prepared in the usual manner, with and without NaOH, are also included in this figure. If there was some interaction between the polymer and NaOH, one would expect that the release characteristics of this batch of microspheres would be similar to those prepared in the usual manner with NaOH, as represented by the dotted line. Instead, the release pattern of the microspheres prepared with the NaOH-pretreated polymer, represented by the solid circles, almost coincides with the solid line, which corresponds to microspheres prepared without NaOH. This indicates that drug release was not enhanced by pretreating the polymer with NaOH prior to preparing the drug-loaded microspheres. 

Figure 7. Scanning electron micrographs of thioridazine microspheres prepared with mole NaOH/mole lactic acid ...

Figure 7. Continued. Scanning electron micrographs of thioridazine microspheres prepared with mole NaOH/mole lactic acid (C) 0.09 and (D) 0.14. Drug loading, 43%. Emulsifier, sodium oleate.

Microspheres prepared with bioadhesive polymers have some additional advantages they assure much more intimate and prolonged contact with the mucous layer and improved drug absorption due to additional delay in mucociliary clearance. Bioadhesive microspheres can significantly improve patient compliance as all the advantages described lead to reduction in the frequency of drug administration [3,74]. 

Chitosan microspheres were shown to enhance nasal bioavailability of several peptide drugs such as insulin and goserelin. A simple chitosan-insulin powder formulation provided about 20% of absolute insulin bioavailability in sheep [96], Improved bioavailability (of 44%, in rats) was obtained when insulin was loaded into chitosan microspheres prepared with ascorbyl palmitate as cross-linking agent [91]. Chitosan microspheres have also been shown to improve nasal goserelin absorption providing about 40% bioavailability relative to goserelin intravenous application [9],... 

Ogawa Y, Okada H, Yamamoto M, Shimamoto T. In vivo release profiles of leuprolide acetate from microsphere prepared with polylactic acids or copoly(lactic/glycolic) acids and in vivo degradation of these polymers. Chem Pharm Bull 1988 36 2576-2581. 

Zhang JJ, Gao G, Zhang M, et al. (2006) ZnO/PS core-shell hybrid microspheres prepared with miniemulsion polymerization. J Colloid Interface Sci 301 78-84 Mahdavian A, Stirrafi Y, Shabankareh M (2009) Nanocomposite particles with core-shell morphology. 111. Preparation and characterization of nano Al203-poly(styrene-methyl methacrylate) ptirticles via miniemulsion polymerization. Polym Bull 63 329-340... 

D. Breslauer, S. Muller, and L. Lee, Generation of monodisperse silk microspheres prepared with microfluidics. Biomacromolecules, 11, 643-647, 2010. 

Zhang JJ, Gao G, Zhang M et til (2006) ZnO/PS core-shell hybrid microspheres prepared with miniemulsion polymerization. J Colloid Interface Sd 301 78-84... 

Figure 30 Release kinetic of pBC 264 in phosphate-buffered saline (pH 7.4) (A) and in vivo, in brain tissue (B) from PLGA microspheres prepared with either ovalbumin (bull) or Pluronic F-68 ( ) (From Ref 70.)...

Figure 3.8 Scanning electron micrograph of pH- and temperature-sensitive pullulan microspheres prepared with pullulan (A) and grafted pullulan (B) (reproduced with permission from (212]).

Truly porous, synthetic ion exchangers are also available. These materials retain their porosity even after removal of the solvent and have measurable surface areas and pore size. The term macroreticular is commonly used for resins prepared from a phase separation technique, where the polymer matrix is prepared with the addition of a hq-uid that is a good solvent for the monomers, but in which the polymer is insoluble. Matrices prepared in this way usually have the appearance of a conglomerate of gel-type microspheres held together to... 

The soapless seeded emulsion copolymerization method was used for producing uniform microspheres prepared by the copolymerization of styrene with polar, functional monomers [115-117]. In this series, polysty-rene-polymethacrylic acid (PS/PMAAc), poly sty rene-polymethylmethacrylate-polymethacrylic acid (PS/ PMMA/PMAAc), polystyrene-polyhydroxyethylmeth-acrylate (PS/PHEMA), and polystyrene-polyacrylic acid (PS/PAAc) uniform copolymer microspheres were synthesized by applying a multistage soapless emulsion polymerization process. The composition and the average size of the uniform copolymer latices prepared by multistage soapless emulsion copolymerization are given in Table 11. 

Extensive studies have been reported with cisplatin in the field of chemoembolization (59,98). Microspheres prepared by a solvent evaporation procedure were characterized in vitro and critical processing parameters in regard to drug release kinetics were identified. 

Several antiinflammatory compounds have been formulated in lactide/ glycolide polymers (107-111). Methylprednisolone microspheres based on an 85 15 DL-lactide/glycolide copolymer were developed for intra-articulate administration (111). The microspheres, prepared by a solvent evaporation procedure, are 5—20 jam in diameter and are designed to release low levels of the steroid over a extended period in the joint. Controlled experiments in rabbits with induced arthritis showed that the microspheres afforded an antiinflammatory response for up to 5 months following a single injection. 

Fig. 10 Release of cromolyn sodium (sodium cromoglycate) from human serum albumin microspheres prepared using a water-oil emulsion technique with 5% glutaraldehyde as cross-linking agent. Dissolution medium pH 7 phosphate buffer. (From Ref. 98.)... 

PNIPAM microsphere gels with diameter of 100-200 jim were prepared by emulsion polymerization [21]. The gel containing 12 mole % benzo[18]crown-6 was immersed in water and the diameter change of the gel was measured during heating at a rate of 0.3 °C/min. The gel was swollen below 25 °C. In the absence of metal ions, it started to shrink at 26 °C and showed a sharp volume change at 28.4 °C. Finally, the volume decreased by as much as 10 times the original volume. 

Liquid fluorocarbon was used as continuous phase by Perez-Moral and Mayes [19] as well. They proposed a new method for rapid synthesis of MIP beads, in that they prepared 36 polymers imprinted for propranolol and morphine with different amounts of EDMA as a cross-linker and different functional monomers (MAA, acrylic acid, hydroxyethyl methacrylate, 4-vinylpyridine) directly in SPE cartridges. The properties of MIP microspheres prepared by this method were very similar in terms of size, morphology and extent of rebinding to microspheres prepared by conventional suspension polymerisation in perfluorocarbons as well as to bulk polymers prepared in the same solvent. The most notable advantages of this method are no waste production (no transfer of beads during washing steps) and possible direct use for a variety of screening, evaluation and optimisation experiments. 

Kawashima, Y., et al. 1991. Preparation of multiple unit hollow microspheres (microballons) with acrylic resin containing tranilast and their drug release characteristics in vitro) and floating behavior in vivo). J Control Release 16 279... 

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