Related Experiment Video
Updated: May 24, 2025
A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Development of a Melting Point Depression Method to Measure the Solubility of a Small-Molecule Drug in
1College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, The University of Texas at Austin, Austin, TX, 78712, USA.
Purpose:
The solubility of a crystalline drug in a polymer is commonly determined by measuring melting point depression with differential scanning calorimetry (DSC). The accuracy of this measurement depends on rapid dissolution of the drug into the molten polymer during the DSC heating scan. A preferred method of accelerating this dissolution process is to preblend the drug and polymer by cryo-milling. However, cryo-milling may be unsuitable for water-sensitive drugs or polymers such as poly(lactic-co-glycolic acid) (PLGA). The purpose of this study was to develop a PLGA-specific melting point depression method that did not require a cryo-milling operation.
Methods:
A three-step DSC method was used to measure the solubility of a small-molecule drug, voriconazole, in amorphous PLGA (Resomer ® RG 502H). First, drug/PLGA powder mixtures of multiple drug loadings were melted and rapidly cooled to form glassy solid solutions. Second, these solid solutions were heated above their Tg until the drug crystallized. Third, these crystallized samples were slowly heated to measure melting point depression (i.e., solubility temperatures).
Results:
The crystallization procedure generated the desired drug polymorph and likely generated small, well-mixed crystalline drug particles, as the drug dissolved rapidly into the molten polymer during melting point depression scans. Drug/PLGA solubility temperatures were determined with confidence between 40 - 100% drug loading. The solubility curve was extrapolated to lower drug loadings using the Flory-Huggins model.
Conclusion:
This technique can assist product development of high-drug-loaded PLGA products, particularly those manufactured by melt extrusion.
More Related Videos
05:08Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
11:32Characteristics of Precipitation-formed Polyethylene Glycol Microgels Are Controlled by Molecular Weight of Reactants
Published on: December 23, 2013
Related Concept Videos
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
01:15Theories of Dissolution: Diffusion Layer Model
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
03:12Freezing Point Depression and Boiling Point Elevation
The boiling point of a liquid is the temperature at which its vapor pressure is equal to ambient atmospheric pressure. Since the vapor pressure of a solution is lowered due to the presence of nonvolatile solutes, it stands to reason that the solution’s boiling point will subsequently be increased. Vapor pressure increases with temperature, and so a solution will require a higher temperature than will pure solvent to achieve any given vapor pressure, including one...