Multiparticulate formulations continue to grow in application due to their inherent advantages, including the greater flexibility they offer compared with monolithic formats:
Capsugel utilizes several oral multiparticulate platform technologies that have been successfully applied formulation needs, as summarized below:
SPRAY-LAYERED MULTIPARTICULATES (SLMs)
SLMs are layered spherical particles approximately 100 to 1500 µm in diameter that contain one or more active ingredients. Typical applications include modified and programmed release, enhanced bioavailability (immediate and modified release) and fixed-dose combination therapies. SLMs are produced by using a bottom-spray fluidized-bed coater to apply one or more coatings to a coating substrate.
LIPID MULTIPARTICULATES (LMPs)
LMPs are round, smooth matrix multiparticulates produced from safe, precedented excipients. Typically 50 to 300 µm in diameter, they can be used for applications requiring bioavailability enhancement, modified release, tastemasking, high-dose actives and fixed-dose combination therapies. Using a continuous spinning-disk process developed by Capsugel, a drug is uniformly distributed within a carrier (typically, a biocompatible lipid or wax) with optional drug release-rate modifiers.
Extrusion/spheronization is a very flexible process used to produce uniformly sized spheroid granules through agglomeration, typically 600 to 2000 micrometers in diameter. These dense granules are excellent for preparing dosage forms with a minimum of excipients, and provide an excellent substrate for drug layering and functional coating. Extrusion/spheronization is routinely utilized to develop drug products with a range of drug release profiles, administer combination therapies and combine two incompatible drugs in a single dosing unit.
MINI-TABLETS WITH OPTIONAL ENCAPSULATION
Mini-tablets are typically 2- to 3-mm tablets produced on a rotary tablet press by direct compression. They can be coated using aqueous- or solvent-based films using fluidized-bed or pan coaters and then encapsulated to produce an immediate- or modified-release multiparticulate dosage.
Capsugel has extensive experience in designing, formulating and scaling MP dosage forms at feasibility, pilot and commercial scales. We have a large range of fluid bed coaters, hot-melt extrusion / spheronization, melt-spray-congeal processing, tablet compression, and supporting equipment to manufacture clinical supplies for clinical studies and small-scale commercial production.
Review the state of the art for MP usage in FDCs and use case studies or hypothetical combinations to describe formulation efficacy improvements enabled through MP usage in FDCs from a chapter from W. Brett Caldwell and Aditya M. Kaushal's book.