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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the
Seung-uk Yoo1, Steven L Krill, Zeren Wang
1Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877, USA. seung-uk.yoo@boehringer-ingelheim.com
Journal of Pharmaceutical Sciences
|May 23, 2009
Summary
Binary solid dispersions containing crystalline excipients in amorphous polymers were studied. Acid-base ionic interactions and high glass transition temperature (Tg) promote amorphous miscibility and physical stability.
Area of Science:
- Pharmaceutical Science
- Materials Science
- Physical Chemistry
Background:
- Solid dispersions are crucial for drug formulation, enhancing solubility and bioavailability.
- Understanding amorphous miscibility and physical stability is key to developing effective drug delivery systems.
- Physicochemical properties of components significantly influence solid dispersion characteristics.
Purpose of the Study:
- To investigate the relationship between physicochemical properties and amorphous miscibility/physical stability in binary solid dispersions.
- To identify key factors governing the formation and stability of amorphous solid dispersions.
- To provide a basis for designing multi-component solid dispersions.
Main Methods:
- Binary solid dispersions were prepared using the solvent evaporation method.
- Characterization involved polarized light microscopy, differential scanning calorimetry, and powder X-ray diffraction.
- Physicochemical parameters including solubility parameter, hydrogen bond energy, Log P, pK(a), and glass transition temperature (Tg) were analyzed.
Main Results:
- Systems with acid-base ionic interactions consistently formed an amorphous state.
- In the absence of ionic interactions, solubility parameter and partition coefficient were critical for amorphous formation.
- Amorphous state was maintained for 50 days under storage conditions (25°C/60% RH) for systems with ionic interactions and high Tg.
- High Tg acted as a kinetic factor, enhancing physical stability.
Conclusions:
- Acid-base ionic interactions are a primary driver for amorphous state formation in solid dispersions.
- Physicochemical properties, particularly solubility parameter and partition coefficient, play significant roles in amorphous formation.
- High Tg is crucial for maintaining physical stability of amorphous solid dispersions.
- This study offers insights into tailoring solid dispersion properties through component selection.
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