Microspheres freeze drying

Spray freeze drying also has been proposed as an alternative technology to produce light and porous particles for peptide and protein delivery. Liquid nitrogen is used as recipient agent, into which the formulation is sprayed. The formed microparticles are harvested and lyophilized eventually. DNase and monoclonal anti-IgE antibodies have been used to demonstrate the feasibility of this concept (Maa et al. 1999). Promaxx microspheres are manufactured in a phase-separation process between water-soluble polymers and therapeutically active protein that results in particles having a high protein payload of up to 90 percent (Brown et al. 1999). 

Carrasquillo, K. G., Stanley, A. M., Aponte-Carro, J. C., DeJesus, P, Costantino, H. R., Bosques, C. J., and Griebenow, K. (2001), Non-aqueous encapsulation of excipient stabilized spray freeze dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein,/. Controlled Release,76,199-208. 

FIGURE 17 Morphine plasma concentration after nasal administration of morphine formulations in sheep Mor Sol, morphine solution Mor Chi Sol, morphine solution containing chitosan Mor Chi PWD, morphine chitosan powder Mor SMS LPC, starch microspheres with lysophosphatidylcholine and morphine as a freeze-dried powder. (Reproduced from ref. 105 with permission of the American Society for Pharmacology and Experimental Therapeutics.)... 

Nanoparticles of all descriptions can be used not only as suspensions but also as freeze-dried powders for reconstitution, incorporated into liposomes, as aerosols, in gels and microspheres (e.g., gelatin), adsorbed onto microparticles, dispersed in soft-gelatin capsules [e.g., in polyoxyethylene glycols (PEGs)], or as mini-depot tablets. 

Controlled-release biodegradable PLG polymers loaded with parathyroid hormone were formulated as a freeze-dried form with particle size ranging from 27 to 47 i. The freeze-dried method did not alter the surface morphology, particle size, and parathyroid hormone content or release rate of the microspheres. The freeze-dried microspheres resuspended very rapidly and uniformly in solution. In vitro release studies indicated that except for a slight early burst ranging from 4-18%, release of parathyroid hormone from the nanoparticles was very slow over the first 14 days. At 15 days, release of parathyroid hormone accelerated rapidly. 

All aqueous microsphere dispersions must be dried after the capsules are completely hardened. Freeze-drying is a common method of gaining stable powders that can be stored and appHed. It is important to minimize the amount of resting water in the formulation, as not orJy the drug can be hydrolyzed but also the polymer. Polyesters and polyanhydrides both degrade by hydrolysis catalyzed by water consequently, the release mechanism usually depends on drug diffusion as well as on polymer degradation. 

Ma, X.H., Santiago, N., Chen, Y.S., Chaudhary, K., Milstein, S.J., and Baughman, R.A., Stability study of dmg-loaded proteinoid microsphere formulations during freeze-drying, J. Drug Target., 1994, 2, 9-21. 

A method developed from temperature induced phase separation was completed to obtain PLA/bacterial cellulose composites [174]. In this work, bacterial cellulose was added to 1,4-dioxane and homogenized before PLA was added and dissolved before the mixture was added dropwise into a liquid nitrogen bath. The precipitate was collected and freeze-dried to produce composite microspheres, which were then fed into a twin-screw extruder and were mixed at 180°C, extruded, pelletized and hot press compression moulded into films. PLA films containing bacterial cellulose showed an increase in tensile modulus, with composites containing bacterial cellulose, and chemically modified bacterial cellulose shown to have improvements over PLA alone [174]. 

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