Controlled-Release Pelletized Dosage Forms Using the Extrusion-Spheronization Process

Abstract

ABSTRACT − Pellets, which are multiple-unit dosage systems, have the several therapeutic advantages over single-unitdosage systems in oral drug delivery. This review focuses on the current status and explores extrusion-spheronization tech-nique with special attention to controlled-release application of pellets including coated pellets for delayed release for-mulations, coated pellets for colon delivery, coated pellets for sustained drug delivery, sustained-release matrix pellets,pellets compressed into tablets, bioadhesive pellets, floating pellets, and pelletization with solubilization techniques.Key words − Pellets, Multiparticulates, Modified- release, Pelletization, Solubilization Pelletization process is an agglomeration process that resultsin agglomerates of a narrow size distribution in the range of0.5-1.5 mm with a low intra-agglomerate porosity (about 10%)and the higher density compared to the granules. Pellets areproduced by pelletization process and these agglomerates havethe relatively spherical shape, low friability and free flowingproperties, which facilitate the handling of pellets in the man-ufacturing process. Pelletization process can prevent the seg-regation of co-agglomerated components, resulting in animprovement of the content uniformity. Pelletization processcan also avoid the dust formation resulting in an improvementof the process safety, as fine powders can cause dust explo-sions and respiratory health problems. Pellets are widely usedin multiparticulate systems and multiparticulate systems havethe several therapeutic advantages over single-unit dosage sys-tems in oral drug delivery. The low inter- and intra-subjectvariability can be achieved by multiparticulate systems becausemultiparticulates can pass through the pylorus immediately afteradministration. Moreover, less effect of food on drug absorp-tion and rather uniform gastric emptying time than single-unitdosage systems can be attainable in multiparticulate systems.Safety concerns due to dose dumping of drugs, which havenarrow therapeutic index, is minimized in multiparticulate sys-tems, and more foreseeable drug delivery in sustained releaseformulation is possible because the total drug dose is dividedover many units, not in a single-unit system. The small size ofmultiparticulates also enables them to be well dispersed alongthe gastrointestinal (GI) tract, enhancing drug absorption andreducing the irritant effect that single-unit systems may causeto the mucosal lining, especially if remained for an extendedtime at a specific site. The spherical pellets can be coated withrate-controlling polymers or compressed into tablets to achievedelayed-release, extended-release, and targeted-release profiles.Multiparticulate systems with different dose strengths can beobtained from the same batch of drug-loaded pellets withoutadditional formulation or process modification. Pellets withdifferent drugs or with different release profiles can be blendedand formulated in a single-unit dosage form such as capsule,which promotes the delivery of two or more chemically com-patible or incompatible drugs at the same or different sites inthe GI tract.Although several pelletization techniques such as high-shear,fluid-bed, spray-drying, and rotary-granulation techniques, aredeveloped and available in the pharmaceutical industry, theextrusion-spheronization technique has certain advantagessuch as preparation of spherical pellets with uniform size andhigh-drug loading (up to 90%) at a moderate cost using min-imum excipients. In various pelletization techniques, thisreview focuses on the current status and explores extrusion-spheronization technique with special attention to controlledrelease application of pellets. A thorough discussion of processvariables for extrusion-spheronization or characterization of