KinetiSol Enabled Reformulation of Marketed IR Product

Summary
  • KinetiSol enabled development of a unique controlled release amorphous dispersion formulation via use of high MW HPMC
  • KinetiSol enabled development of an amorphous dispersion formulation where melt extrusion and spray drying were not amenable
  • The KinetiSol formulation exceeded the target human PK by:
    • Reducing Cmax by 50%
    • Maintaining equivalent AUC to the IR product
    • Prolonging drug plasma concentrations above the therapeutic threshold
IR Product Reformulation

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  • IR formulation rapidly releases drug in the stomach
  • Rapid drug absorption in upper GI tract
  • High concentrations at Cmax lead to onset of side effects
  • Rapid elimination leads to brief duration of action and frequent dosing

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  • Good solubility in gastric fluid
  • Stomach-to-Small Intestine: near 300-fold decrease in solubility
  • Need controlled drug release in the stomach while enhancing solubility in the intestinal tract
Formulations Development

In-Vitro Dissolution Testing

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Pharmacokinetic Comparison in Dogs

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  • Achieved the targeted drug release profile with the KinetiSol compositions via use of high MW HPMC
  • Met PK goals for reducing peak blood levels and prolonging systemic exposures in dogs
  • Identified four KinetiSol product candidates for human PK screening
Human PK Comparisons

KinetiSol MR vs. Commercial IR

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  • Cmax of MR < 50% of IR, AUCMR = AUCIR
  • PK profile of the KinetiSol MR formulation indicates a product that will provide improved safety, efficacy, and convenience

CASE STUDIES

Read about exciting new breakthroughs

KinetiSol® has been the subject of numerous research articles published in top peer-reviewed journals in recent years. These papers demonstrate unique capabilities of the KinetiSol®process and its benefits for amorphous solid dispersion processing. Key advantages of the KinetiSol® process are illustrated in these case studies.

 

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