Microencapsulation microsphere

The number of microencapsulated commercial oral formulations available and the volume of these formulations sold annuaUy is comparatively smaU. This may reflect the difficulty of developing new dmg formulations and bringing them successfully to market or the fact that existing microencapsulation techniques have had difficulty economically producing mictocapsules that meet the strict performance requirements of the pharmaceutical industry. One appHcation that is a particularly active area of development is mictocapsules or microspheres for oral deUvery of vaccines (45,46). 

A review of chitosan microspheres as carrier for drugs pubUshed recently by Sinha et al. provides insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation protocols have also been reviewed, together with the factors that affect the entrapment efficiency and release ki-nefics of drugs [194]. 

Ribeiro, A. J., Neufeld, R. Arnaud, P. Chaumeil, J. C. (1999). Microencapsulation of lipophilic drugs in chitosan-coated alginate microspheres. International Journal of Pharmaceutics, Vol. 187,1, (September 1999), pp. (115-123), ISSN 0378-5173 Rubinstein, A. (1995). Approaches and opportunities in colon-specific drug-delivery. Critical Reviews in Therapeutic Drug Carrier Systems, Vol 12, 2-3,1995), pp. (101-149), ISSN 0743-4863... 

Microspheres and microcapsules of lactide/glycolide polymers have received the most attention in recent years. Generally, three microencapsulation methods have been employed to afford controlled release formulations suitable for parenteral injection (1) solvent evaporation, (2) phase separation, and (3) fluidized bed coating. Each of these processes requires lactide/glycolide polymer soluble in an organic solvent. 

The steroid microsphere systems are probably the most successful drug delivery formulations thus far ba.sed on lactide/glycolide polymers. Several of these products appear to be on track for human and animal applications in the 1990s. The success of these formulations is due to the known safety of the polymer, the reproducibility of the microencapsulation process, reliability in the treatment procedure, and in vivo drug release performance (80). 

Muramyl dipeptide derivatives have also been microencapsulated in lactide/glycolide copolymers for use alone as an immuno potentiator. L-lactide/glycolide copolymers were used to deliver MDP-B30, a lipophilic compound, from very small microspheres (less than 5 pm in diameter). The amount of MDP-B30 required for tumor growth inhibitory activity of mouse peritoneal macrophages was 2000 times less for the controlled release MDP-B30 microspheres than for the unen-capsulated drug (134). 

Microencapsulation with PCL using the solvent evaporation method can be experimentally difficult. For example, PCL was the only polymer of five that failed to yield spherically shaped microcapsules using this technique (82). The insecticide Abate has been incorporated into PCL (21% loading) by the solvent separation method in a comparative study, PCL afforded good-quality microspheres although poly (methyl methacrylate) microcapsules were smoother and had fewer defects (83). 

At present there is no reason evident why poly(N-acylhydroxy-proline esters) should not be suitable for the formation of microcapsules or microspheres as well. For microencapsulated drug fonmula-tions the longer degradation times of poly(N-acylhydroxyproline esters) as compared to poly (lactic acid) could again be a distinctive advantage for long-term applications. 

Gelatin has been used as a coating material to microencapsulate drugs and as a matrix, usually in the form of microspheres. The... 

Yuksel N, Turkoglu M, Baykara T. Modelling of the solvent evaporation method for the preparation of controlled release acrylic microspheres using neural networks. J Microencapsulation 2000 17 541-51. 

J. L. Cleland and A. J. Jones, Stable formulations of recombinant human growth hormone and interferon-y for microencapsulation in biodegradable microspheres, Phar. Res, 13(10), 1464 (1996). 

E Mathiowitz, WM Saltzman, A Domb, P Dor, R Langer. Polyanhydride microspheres as drug carriers. II. Microencapsulation by solvent recovery. J Appl Polym Sci 35 755-774, 1988. 

Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsule (Table 28-2). Microencapsulated enteric-coated products are not superior to recommended doses of conventional non-enteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. GI side effects appear to be dose related but occur less frequently with enteric-coated products. 

FIG. 6. Scheme of possible drug release from Eudragit microencapsulated chitosan microspheres (adapted from Ref. 78). 

Wakerly, Z., Fell, J.T., Attwood, D., and Parkins, D., Peetin/ethyl eellulose film-eoating formulations for colonic drug delivery, Pharm. Res., 13 1210-1212 (1996). Lorenzo-Lamosa, M.L., Remunan-Lopez, C., Vila-Jato, J.L., and Alonso, M.J., Design of microencapsulated chitosan microspheres for colonic drug delivery, J. Contr. Rel, 52 109-118 (1998). 

More complex geometries have been developed [40] and the influence of the geometrical structure has been examined. Although straight-through microchannel emulsification has been developed [39,41], the production rates are still low compared to those obtained with standard emulsification methods. However, the very high monodispersity makes this emulsification process very suitable for some specific fechnological applicafions such as polymeric microsphere synfhesis [42,43], microencapsulation [44], sol-gel chemistry, and electro-optical materials. 

Chemoembolization with microencapsulated drugs has been in clinical use since 1978 [6]. Using biodegradable starch microspheres containing anticancer drugs which occlude selected arteries, anticancer drugs can be locally released upon the degradation of starch by serum amylases [333, 334]. 

Jeyanthi, R., Mehta, R.C., Thanoo, B.C., and Deluca, P.P. (1997). Effect of processing parameters on the properties of peptide-containing PLGA microspheres. J. Microencapsulation, 14, 163-174. 

Desai, K.G., Park, H.J. (2005). Encapsulation of vitamin C in tripolyphosphate cross-linked chitosan microspheres by spray drying. Journal of Microencapsulation, 2, 179-192. 

Giunchedi P, Gavini E, Bonacucina G, Palmieri GF. Tabletted polylactide microspheres prepared by a w/o emulsion-spray drying method. J Microencapsul 2000 17(6) 711-720. 

Lee, J.H., T.G. Park, and H.K. Choi. 1999. Development of oral drug delivery system using floating microspheres. J Microencapsul 16 715. 

Varshosaz, J., H. Sasrai, and R. Alinagari. 2004. Nasal delivery of insulin using chitosan microspheres. J Microencapsul 21 761. 

Spray drying. Microencapsulation by spray drying is an ideal method for poorly water-soluble drugs. The drug is dispersed in polymer (coating) solution, and then this dispersion is atomized into an airstream. The air, usually heated, supplies the latent heat of vaporization required to remove the solvent and forms the microencapsulated product. This technique is employed most commonly when microcapsules are intended for oral use because the resulting microspheres are porous in nature, and large batch sizes are required.89... 

Enhancing Drug Release from Folylactide Microspheres by Using Base in the Microencapsulation Process... 

The solvent evaporation microencapsulation process using sodium oleate as the emulsifier produced microspheres in high yields (75-95%), essentially free of agglomeration (1). Drugs with low solubility in water (0.02 mg/ml or less) e.g. thioridazine, were incorporated with 80-99% efficiency. Core loadings up to 60% were attained along with prolonged in vitro release. 

Adeyeye, C. M., and Price, J. C. (1997), Chemical dissolution stability and microscopic evaluation of suspensions of ibuprofen and sustained release ibuprofen-wax microspheres, /. Microencapsul., 14(3), 357-377. 

TABLE 3 Factors in Selection of Microencapsulation Method to Prepare Peptide/Protein-Loaded Microspheres... 

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