Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Drug Delivery Systems

Background:

• Recrystallization issues hinder the storage stability of amorphous drug formulations.
• In situ amorphization offers a potential solution by preparing amorphous drugs in their final dosage form.
• Microwave irradiation is explored as an energy source for in situ amorphous solid dispersion preparation.

Purpose of the Study:

• To investigate the feasibility of using microwave irradiation for in situ preparation of amorphous solid dispersions (glass solutions).
• To evaluate the influence of moisture content and microwave energy input on the amorphization of Indomethacin (IND) within polyvinylpyrrolidone K12 (PVP) tablets.

Main Methods:

• Tableting of Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) at a 1:2 (w/w) ratio.
• Storage of tablets at varying relative humidity (32%, 43%, 54% RH).
• Microwave irradiation using nine power-time combinations (up to 90 kJ) to induce in situ amorphization.

Main Results:

• X-ray powder diffraction (XRPD) confirmed up to 80% (w/w) amorphization of IND within the tablets.
• Modulated differential scanning calorimetry (mDSC) showed reduced crystalline IND and amorphous PVP with increased microwaving, alongside increased IND-PVP glass solution formation.
• Intrinsic dissolution testing indicated dissolution rates comparable to quench-cooled amorphous solutions, despite residual crystalline IND.

Conclusions:

• Microwave irradiation is a viable method for in situ preparation of amorphous solid dispersions in tablet form.
• The study demonstrates successful amorphization of IND in PVP, yielding a stable glass solution.
• This in situ approach shows promise for enhancing drug dissolution and circumventing storage-related recrystallization problems.