(336e) Modeling the Bead-Dissolution Kinetics for Composite Melt-Spray Congealed (MSC) Multiparticulates

Sarkar, A., Worldwide Research and Development, Pfizer Inc.
Shoemaker, B., Pfizer Inc.
Melt-spray congealed (MSC) beads are a promising drug-delivery platform that offers tunable dissolution profiles and drug-release characteristics, taste masking, and ease of dosing for pediatric and geriatric populations. These small, composite, multiparticulate beads (~50-500 mm) are comprised of a mixture of wax and pore former. This wax and pore-former matrix is embedded with active-pharmaceutical ingredient (API) particles, i.e., the drug powder. Once submerged, the pore former rapidly dissolves away leaving behind a porous network. The API then dissolves into the fluid-filled pores, diffuses through the pores, and is finally released at the bead surface into the dissolution media.

Theoretically, the pore-former level, API particle size, bead size, and other adjustable parameters can be engineered to obtain the desired dissolution profile. In reality, this presents a challenge as the exact quantitative dependence of the dissolution rates on the adjustable formulation parameters (pore-former level, drug level, API size, bead size) and unchangeable API material properties (solubility, diffusion rate) are not well understood. To address this issue, this present work describes a model, entitled BeaDiPUB (an acronym for Bead Dissolution Predictions Using BeaDiPUB), that is developed to predict the dissolution of MSC beads as a function of these formulation and material parameters. The current model version is focused on an immediate-release-type formulation without any protective coating.

A calibration/validation procedure is developed for BeaDiPUB which allows application of the model to real compounds. Subsequently, parametric studies are performed to analyze the sensitivity of the dissolution kinetics to the formulation and material properties. Finally, the various regimes for drug release with different rate-limiting steps are examined. The intent of the model is to allow for virtual exploration of the formulation-design space, and thereby reduce the number of experimental iterations needed to manufacture multiparticulates with the desired dissolution characteristics.