Purpose: The use of two solvent-casted film methods to select optimal polymer compositions for amorphous solid dispersions prepared to support preclinical pharmacokinetic and toxicology studies is described.
Methods: Evaporation of solvent from cover slips by using nitrogen flow, and solvent removal from vials by using rotary evaporation were employed. The films prepared on cover slips were evaluated under the microscope to determine crystallinity. The methods were validated by scaling up corresponding SDDs, evaluating SDD's dissolution, and comparing those results to the dissolution of drug-polymer films. Subsequently, SDD suspensions were prepared and dosed orally to rats to determine pharmacokinetic parameters. This was done by using three compounds from our pipeline and evaluating multiple polymers.
Results: The dissolution of generated films showed good agreement with the dissolution of spray dried dispersions when the films were fully amorphous (Compound A and B). In contrast, there was disagreement between film and SDD dissolution when the films had crystallized (Compound C). The in vivo exposure results indicated that the polymer choice based on the film screening methods would have been accurate for drug-polymer films that were amorphous (Compound A and B). Two additional case studies (Compound D and E) are presented, showing good agreement between in vivo and in vitro results.
Conclusion: This study established the ability of two film casting screening methods to predict the in vitro and in vivo performance of corresponding SDDs, provided that the films are fully amorphous.
Keywords: amorphous solid dispersion; in-vivo; polymer; preclinical; screening.