Microsphere preparation procedure

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. 

The preparation of monodisperse hydrogel microspheres, such as poly-acrylam-ide-co-acrylic acid, poly(N-isopropylacrylamide-co-acrylic acid), has been performed for drug devices thanks to their biocompatibility [77, 79]. The average diameters of the microspheres were dependent on the pore sizes (from 0.33 to 1.70pm) of SPG membranes used in the preparation procedure. 

Albertsson and coworkers [240-244] carried out extensive research to develop polymers in which the polymer properties are altered for different applications. The predominant procedure is ring-opening polymerization which provides a way to achieve pure and well defined structures. They have utilized cyclic monomers such as lactones, anhydrides, carbonates, ether-lactones. The work involved the synthesis of monomers not commercially available, studies of polymerization to form homopolymers, random and block copolymers, development of cross-linked polymers and polymer blends, surface modification in some cases, and characterization of the materials formed. The characterization is carried out with respect to the chemical composition and both chemical and physical structures, the degradation behavior in vitro and in vivo, and in some cases the ability to release drug components from microspheres prepared from the polymers. 

Microspheres prepared by spray drying maintain their spherical geometry with a narrow size distribution with a mean diameter of 2-5 pm. Calceti et al. used suspension solvent evaporation, double emulsion-solvent evaporation, and suspension/double emulsion-solvent evaporation for the preparation of insulin-loaded polyphosphazene microspheres [80], These preparation procedures produced spherical microparticles with a porous surface and a honeycomb internal structure (Figure 11.11). 

Figure 1. Illustration of preparation procedures of OMMs using self-assembled template 2.2 Synthesis of un form-size microspheres...

The crystalline nature of zirconia microspheres prepared for chromatographic purposes is dependent upon the thermal history of the zirconia. A detailed discussion on the porous nature of zirconia and silica is not warranted in this text but is covered in detail in a review by Nawrocki et al. It is perhaps important to note that zirconia is amorphous until subjected to temperatures that exceed the phase transition temperature required to form the tetragonal phase (usually between 440°C and 470°C depending on the procedure used to prepare the zirconia). Once thermal treatment exceeds this phase transition temperature, a metastable tetragonal phase predominates—where, after cooling, zirconia slowly transforms to the stable monoclinic form. As thermal treatment of the zirconia is required to obtain a suitable pore-structured stationary phase, most zirconias prepared for chromatographic purposes are predominantly monoclinic, or perhaps more correctly... 

Recent work on starch-based microspheres [60], as discussed earlier, suggests that ultrasonic preparation procedure is a versatile method that could be used for the preparation of microspheres with a variety of shell and core materials. Chitosan... 

Poly(DL-lactide) was used as the excipient in microspheres of CCNU, a nitrosourea, prepared by a solvent evaporation procedure (96,97). PLA-CCNU microspheres 3.0 pm in diameter were injected i.v. and leukemia cell survival was determined by spleen colony assay. A 100-fold decrease in leukemia cell survival was observed with the microspheres in both spleen and liver compared to untreated controls. Promising results were also obtained with Lewis lung carcinoma in mice. These studies showed that 2- to 4-ym microspheres were preferentially targeted to the lungs. 

Insulin (molecular weight 7000) has been formulated in controlled release microbeads and pellets (135,136). A solvent evaporation micro-encapsulation procedure was used to produce microspheres with up to 20% by weight insulin. Solvent-casting techniques were used to prepare pellets. The investigations demonstrated that the PLA... 

FIGURE 8 Release of cortisone acetate from 10% loaded microspheres of various polyanhydrides. The microspheres were prepared by an interfacial condensation. Details of the experimental procedure are described in the text. 

Using two different procedures, based, respectively, on slow solvent evaporation[14] and on coprecipitation, a new proprietary method was developed during the fulfillment of a research project funded by the European Community (EC) under the Brite-EuramProgram[15,16], were tested for the preparation of microspheres. 

The procedure for the preparation of cross-linked chitosan microspheres coated with polysaccharide or lipid for intelligent drug delivery systems is illustrated in Fig. 11 [230]. 

More recently, a similar procedure for the preparation of zirconia-coated silica microspheres was employed by Tsurita and Nogami, who coated 3-pm silica spheres with zirconia derived from zirconyl chloride octahydrate. The resulting zirconia-silica spheres were subjected to thermal treatment in order to bring about crystallization and the subsequent development of the porous structure within the material. 

Figure 4.40 The procedure for preparing silicalite-l microspheres using anion-exchange resins as macrotemplates. Reproduced with permission from [147]. Copyright (2000) Elsevier...

The magnetic polystyrene latex particles with diameter of 120 nm were covered by PNIPA gel layer. The mPS latex prepared according to the procedure described previously was strongly stirred at 60 °C and kept under N2 atmosphere for 1 h. Then, 0.05 g APS and 0.5 mL 1 M NIPA solution were added to the mPS latex and the reaction mixture was stirred at 60 °C for more than 1 h. Then, 0.5 mL 1 M NIPA solution and 0.36 mL 0.1 M BA solution were added. After 2 h, 0.5 mL 1 M NIPA solution and 0.36 mL 0.1 M BA solution were added again to the mixture. This mixture was stirred 60 °C for more than 2 h under N2 atmosphere. Figure 9 shows the structure of the core-shell microsphere in dry state. 

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