Binary Isobaric Phase Diagrams of Stearyl Alcohol-Poloxamer 407 Formulations in the Molten and Solid State
Multiparticulate formulations allow for the design of specialized pharmaceutical dosage forms that cater to the needs of a wide range of patient demographics, such as pediatric and geriatric populations, by affording control over the release rate and facilitating the formulation of fixed-dose combination drugs. Melt spray-congealing (MSC) is a method for preparing multiparticulate dosage forms from a suspension or solid solution of active pharmaceutical ingredients (API) and a molten carrier matrix. Stearyl alcohol and poloxamer 407 mixtures are widely used as carrier matrices in MSC microsphere formulations. In this report, the phase equilibria of stearyl alcohol-poloxamer 407 mixtures were investigated by generating binary phase diagrams of composition, i.e. weight/weight percent of poloxamer 407 in stearyl alcohol, and temperature in the molten form and the solid state. The phase equilibria of the molten state were characterized by 1H-NMR measurements.
Highlights
Stearyl alcohol and poloxamer 407 are not miscible in the liquid state at concentration at all proportions and have a temperature dependence.
Solid state mixtures of stearyl alcohol and poloxamer 407 do not interact at the molecular level and exhibit the same thermal events as the neat component.
Microspheres contain a mixture of stable and meta-stable phases as a result of the fast cooling during the melt-spray congeal process
The miscibility curves of stearyl alcohol-poloxamer 407 molten mixtures revealed that stearyl alcohol and poloxamer 407 are not miscible in all proportions and that miscibility substantially increases with temperature. The phase equilibria of the solid state were characterized by DSC and PXRD experiments. The phase diagrams of the solid state indicate that stearyl alcohol and poloxamer 407 crystallize and melt separately and, thus, do not form a eutectic or a single phase. The phases equilibria of the bulk mixtures were compared to the phases observed in placebo MSC microspheres and it was determined that the microspheres consist of a mixture of thermodynamically stable and metastable stearyl alcohol crystals immediately after manufacture.
Nada Mehio, Heather L. Frericks Schmidt, Geoffrey P. F. Wood, Bruno C. Hancock, Ravi M. Shanker, Jeremy A. Bartlett, Sheri L. Shamblin,
Binary Isobaric Phase Diagrams of Stearyl Alcohol-Poloxamer 407 Formulations in the Molten and Solid State,
International Journal of Pharmaceutics,
2022, 121908, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.121908.