In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

Abstract

Abstract. Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated.

Enhancement of docetaxel solubility using binary and ternary solid dispersion systems

“…Common methods for preparation of SDs include solvent evaporation, freeze-drying (FD), hot melt extrusion, fusion and spray drying. Spray drying and hot melt extrusion are industrially scalable 11 but are of little value for small-scale discovery settings 12 . Methods involving heating are limited due to drug stability.…”

“…Methods involving heating are limited due to drug stability. FD is one of the widely used techniques for milligram quantities and has good efficiency in terms of yield 12 .…”

A Fast and Reliable Empirical Approach for Estimating Solubility of Crystalline Drugs in Polymers for Hot Melt Extrusion Formulations

“…[1][2][3][4][5][6] Typical ASD formulation strategy involves dispersing and stabilizing the amorphous form of the drug in a polymer matrix. Several methods such as melt quenching, 7,8 hot-melt extrusion, [9][10][11][12] spray drying, 13 ball milling, 13,14 and freezedrying 15 have been successfully employed for manufacturing ASD formulations.…”

Relative Bioavailability Risk Assessment: A Systematic Approach to Assessing In Vivo Risk Associated With CM&C-Related Changes

“…Some of these changes that could impact in vivo performance include solid form (e.g., polymorph), chemical entity (e.g., salt, co-crystal), and API particle size. [1][2][3] Changes in any of these properties contributes to the overall CM&C and Inherent Biopharmaceutics risk score in the RBA-RA. The changes are cumulative; therefore, the greater the number of changes, the higher the CM&C risk score.…”

“…Therefore, consideration must always be given to how the changes could impact the relative in vivo performance. [1][2][3][4][5] The "gold standard" to understanding the potential impact of these changes on the absorption of a drug is a human in vivo comparability study. Comparability studies can be classified in 2 groups: bioequivalence (BE) studies and relative bioavailability (RBA) studies.…”