Solid state studies of drug-cyclodextrin inclusion complexes in PEG 6000 prepared by a new method

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Drug-cyclodextrin (CD) inclusion complexes are crucial for enhancing drug solubility and stability.
• Polyethylene glycol (PEG) is a common carrier for solid dispersions.
• The melting method offers a potential route for preparing these complexes.

Purpose of the Study:

• To investigate the melting method for producing drug-cyclodextrin (CD) inclusion compounds in a polyethylene glycol (PEG) carrier.
• To characterize the formation and properties of these drug-CD-PEG complexes.
• To evaluate the impact of complexation on drug release.

Main Methods:

• Preparation of solid dispersions using alpha-, beta-, and gamma-cyclodextrins (CDs) with indomethacin or griseofulvin in PEG 6000.
• Characterization techniques: X-ray powder diffraction, modulated-temperature differential scanning calorimetry (mDSC).
• Dissolution testing using the USP XXI paddle method.

Main Results:

• Complexation of indomethacin with beta- and gamma-CDs in PEG 6000 was confirmed.
• A well-defined indomethacin-gamma-CD complex with tetragonal structure was identified.
• No complexation was observed for indomethacin with alpha-CD or griseofulvin with beta-CD.
• Formation of complexes decreased the relative crystallinity of the dispersions.
• Dissolution tests indicated a delaying effect of CDs on indomethacin release from PEG 6000.

Conclusions:

• The melting method is viable for creating specific drug-CD inclusion complexes within a PEG carrier.
• The interaction between PEG, drug, and CD, along with water loss, influences complex formation.
• Cyclodextrins modulate the release rate of indomethacin from PEG 6000, with varying effects based on the CD type.