Keywords
Drug Delivery, Amorphous Solid Dispersion, Hot Melt Extrusion, Particle Size, Crystallinity, Solid-State Characterization
Select the category the research project fits.
Physical Sciences
Is this submission part of ICaP/PW (Introductory Composition at Purdue/Professional Writing)?
No
Abstract
The dissolution of poorly soluble drug molecules into a polymer matrix is a popular oral drug delivery strategy known amorphization. In this type of molecular dispersion, the amorphous form of the drug achieves a thermodynamic solubility advantage over the crystalline form, resulting in higher bioavailability. Hot melt extrusion (HME) is one of two major techniques used to manufacture these amorphous solid dispersions (ASDs). Material, equipment, and process design variables contribute to the product performance of the ASD, and the goal of this study is to evaluate the impact of drug particle size on ASD formation. Physical mixtures of bicalutamide and PVPVA were prepared and analyzed using differential scanning calorimetry, and the calorimetric data was used to construct a temperature-composition phase diagram. The acceptable processing design space for extrusion was derived from this phase diagram and guided the preparation of bicalutamide-PVPVA ASDs at various temperatures and residence times. The extent of residual crystallinity was determined by polarized light microscopy and powder X-ray diffraction. As expected, residual crystallinity decreases with increasing temperature and residence times across all particle sizes. ASDs prepared with larger starting particle sizes consistently possess more residual crystallinity than ASDs prepared with smaller starting particle sizes. The extent of crystallinity in extruded ASDs reflect the kinetic nature of crystal dissolution in a polymer melt. Additional work will include preparation of ASDs from an intermediate particle size, additional sample characterization, and comparison of results to existing dissolution models.
Recommended Citation
Altman, Kevin, "The Effect of Drug Particle Size, Temperature, and Residence Time on Hot Melt Extrusion Processing of Amorphous Solid Dispersions" (2019). Purdue Undergraduate Research Conference. 4.
https://docs.lib.purdue.edu/purc/2019/Posters/4
The Effect of Drug Particle Size, Temperature, and Residence Time on Hot Melt Extrusion Processing of Amorphous Solid Dispersions
The dissolution of poorly soluble drug molecules into a polymer matrix is a popular oral drug delivery strategy known amorphization. In this type of molecular dispersion, the amorphous form of the drug achieves a thermodynamic solubility advantage over the crystalline form, resulting in higher bioavailability. Hot melt extrusion (HME) is one of two major techniques used to manufacture these amorphous solid dispersions (ASDs). Material, equipment, and process design variables contribute to the product performance of the ASD, and the goal of this study is to evaluate the impact of drug particle size on ASD formation. Physical mixtures of bicalutamide and PVPVA were prepared and analyzed using differential scanning calorimetry, and the calorimetric data was used to construct a temperature-composition phase diagram. The acceptable processing design space for extrusion was derived from this phase diagram and guided the preparation of bicalutamide-PVPVA ASDs at various temperatures and residence times. The extent of residual crystallinity was determined by polarized light microscopy and powder X-ray diffraction. As expected, residual crystallinity decreases with increasing temperature and residence times across all particle sizes. ASDs prepared with larger starting particle sizes consistently possess more residual crystallinity than ASDs prepared with smaller starting particle sizes. The extent of crystallinity in extruded ASDs reflect the kinetic nature of crystal dissolution in a polymer melt. Additional work will include preparation of ASDs from an intermediate particle size, additional sample characterization, and comparison of results to existing dissolution models.