In situ amorphisation of indomethacin with Eudragit® E during dissolution

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Poorly water-soluble drugs often exhibit low bioavailability.
• Crystalline forms of drugs can limit dissolution rates.
• Amorphous forms generally show improved solubility but can be physically unstable.

Purpose of the Study:

• To investigate the in situ crystalline-to-amorphous transformation of gamma-indomethacin (IMC) using Eudragit® E.
• To evaluate the impact of this transformation on drug dissolution and physical stability.
• To explore a novel drug delivery approach for poorly soluble compounds.

Main Methods:

• Preparation of physical mixtures of IMC and Eudragit® E in various ratios.
• Dissolution testing at pH 6.8 to induce and observe transformation.
• X-ray powder diffractometry (XRPD) for amorphization confirmation.
• Differential scanning calorimetry (DSC) to determine glass transition temperatures.
• Infrared (IR) spectroscopy with principal component analysis (PCA) for spectral analysis.
• Dissolution testing at pH 4.1 to assess dissolution rates of transformed samples.

Main Results:

• Color change from white to yellow indicated IMC amorphization.
• XRPD confirmed the transformation to an amorphous state.
• Single glass transition temperatures observed, indicating solid solutions.
• PCA of IR spectra showed clustering of in situ transformed samples with quench-cooled glasses.
• In situ transformed samples exhibited higher dissolution rates at pH 4.1 compared to quench-cooled glasses for 3:1 and 1:1 ratios.

Conclusions:

• Crystalline drugs can be transformed into amorphous forms in situ within a polymer matrix.
• This in situ transformation enhances drug dissolution rates.
• The method provides a potentially stable amorphous drug delivery system, overcoming storage instability issues.