Microspheres and Microparticles

Microspheres and microcapsules are polymeric particulate systems, typically ranging from one to one thousand micrometres in diameter, distinguished from one...

Microspheres and microcapsules are polymeric particulate systems, typically ranging from one to one thousand micrometres in diameter, distinguished from one another by their internal architecture: a microsphere consists of a homogeneous polymeric matrix throughout which the drug is dispersed or dissolved, whereas a microcapsule possesses a distinct core-shell structure, with the drug confined within a reservoir enclosed by a discrete polymeric membrane. The polymers most frequently employed for microparticle fabrication include PLGA, valued for its established biodegradability and regulatory precedent; albumin, an endogenous protein offering excellent biocompatibility; chitosan, a cationic polysaccharide amenable to mild, aqueous-based ionic gelation processing; and various grades of Eudragit and hydroxypropyl cellulose, selected according to the desired release profile and administration route.

Microparticle preparation methods are selected according to the physicochemical properties of the drug and the desired release characteristics, and include solvent evaporation, in which drug and polymer dissolved in a volatile organic solvent are emulsified into an aqueous continuous phase and the solvent subsequently removed to harden the resulting droplets into solid microspheres; spray drying, a rapid, continuous, and readily scalable process well suited to industrial manufacture; ionic gelation, particularly applicable to chitosan systems through crosslinking with sodium tripolyphosphate under mild aqueous conditions favourable to labile biologics; and coacervation or phase separation techniques.

Drug release from microparticulate systems proceeds through diffusion of drug from the polymer matrix, through erosion or degradation of the polymer itself, or through a combination of both mechanisms operating simultaneously, and the resulting release profile may approximate zero-order or first-order kinetics depending on the dominant mechanism and the specific polymer and formulation employed. Clinically, microspheres have achieved particular commercial success as long-acting parenteral depot formulations, exemplified by the PLGA-based product Lupron Depot, which provides sustained release of a peptide hormone over periods extending to several months from a single injection, as well as in applications targeting oral colon delivery and pulmonary administration. Characterisation of microparticulate systems relies on scanning electron microscopy for morphological assessment, laser diffraction for particle size determination, quantitative extraction assays for encapsulation efficiency, and in-vitro release testing, frequently employing USP Apparatus 4 flow-through cell methodology, to establish the release kinetics of the finished product.