Studies of phase transitions in the aripiprazole solid dosage form

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Phase transitions in active pharmaceutical ingredients (APIs) are critical for drug stability and efficacy.
• Aripiprazole, a BCS Class IV drug, exhibits polymorphism and pseudopolymorphism, complicating its solid-state characterization.
• Understanding and controlling these transitions in solid dosage forms is essential for ensuring consistent therapeutic outcomes.

Purpose of the Study:

• To develop sensitive analytical methods for detecting phase transitions in aripiprazole tablets.
• To investigate the impact of storage conditions and packaging on the solid-state form of aripiprazole.
• To evaluate the suitability of different packaging materials for aripiprazole tablets containing form III.

Main Methods:

• Development and application of powder X-ray diffraction (PXRD) for solid-state analysis.
• Utilizing Raman spectroscopy to identify and quantify polymorphic and pseudopolymorphic forms.
• Employing differential scanning calorimetry (DSC) to detect thermal events associated with phase transitions.

Main Results:

• Polymorphic transition from form III to form I was not observed in the studied tablets, though detected in reference product.
• Aripiprazole monohydrate formation was observed under accelerated storage conditions in certain packaging.
• Al/Al blisters prevented monohydrate formation under long-term storage, indicating superior moisture protection.

Conclusions:

• Sensitive analytical methods (PXRD, Raman, DSC) were successfully developed for aripiprazole phase transition detection.
• Al/Al blisters are recommended as a suitable packaging material for aripiprazole tablets containing form III, preserving its solid-state integrity.
• The study highlights the importance of packaging selection for stabilizing polymorphic drugs like aripiprazole.