A novel method for preparing stabilized amorphous solid dispersion drug formulations using acoustic fusion
Zack Guo1, Christopher Boyce1, Timothy Rhodes2
1Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, NJ, USA.
International Journal of Pharmaceutics
|November 2, 2020
Summary
Acoustic fusion is a novel method for creating amorphous solid dispersions (ASD) of poorly soluble drugs, significantly improving their solubility and in vivo performance.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- Amorphous solid dispersions (ASD) are crucial for enhancing the solubility and bioavailability of poorly soluble drugs.
- Traditional methods like spray drying and hot melt extrusion have limitations in scale-up and material compatibility.
- Developing novel, scalable methods for ASD formation is essential for drug formulation.
Purpose of the Study:
- To introduce and evaluate a new method, acoustic fusion, for generating amorphous solid dispersions (ASD) on a milligram scale.
- To demonstrate the versatility of acoustic fusion across various drug candidates (BCS Class 2 and 4) and polymer excipients.
- To assess the in vitro and in vivo performance of ASDs prepared by acoustic fusion.
Main Methods:
- Utilized acoustic fusion to prepare ASDs with diverse drug-polymer combinations, including torcetrapib, itraconazole, and lopinavir with polymers like HPMCAS, copovidone, and Soluplus®.
- Evaluated solubility enhancement of ASDs compared to crystalline drugs in aqueous buffers.
- Conducted in vivo pharmacokinetic studies in rats to assess the bioperformance of acoustic fusion-prepared ASDs.
Main Results:
- Acoustic fusion successfully formed ASDs for multiple drug-polymer combinations, indicating its general applicability.
- ASDs prepared via acoustic fusion exhibited significantly enhanced solubility and supersaturation compared to crystalline drugs.
- Rat pharmacokinetic studies showed an approximately 8-fold increase in drug exposure (AUC(0-24)) for acoustic fusion products versus crystalline suspensions.
Conclusions:
- Acoustic fusion is a viable and generalizable method for producing amorphous solid dispersions (ASD) at the milligram scale.
- The method effectively enhances drug solubility and in vivo bioperformance, comparable to established techniques like spray drying and hot melt extrusion.
- Acoustic fusion represents a promising novel approach for developing advanced drug formulations with improved therapeutic efficacy.
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