Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method

Area of Science:

• Materials Science
• Pharmaceutical Science
• Crystallography

Background:

• Progesterone, a natural steroid hormone, exists in two polymorphic forms (form 1 and form 2) at ambient conditions.
• Form 2 is metastable and more soluble than form 1, but it is unstable and transforms into form 1 during grinding, limiting its use as a powder raw material.

Purpose of the Study:

• To investigate the polymer-induced heteronucleation method as an alternative approach for preparing the metastable form 2 of progesterone.
• To screen various polymers for their ability to induce the crystallization of progesterone polymorphs.

Main Methods:

• Polymorphic screening of progesterone using polymer-induced heteronucleation.
• Crystallization experiments using polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI), and acrylonitrile-butadiene (NBR) copolymer from acetone solutions at varying concentrations (0.5, 10, 40 mg/mL).
• Characterization of crystallized samples using X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and attenuated total reflectance infrared Fourier transform spectroscopy (ATR-FTIR).

Main Results:

• Form 1 was predominantly nucleated from higher concentration solutions (40 mg/mL) and on specific polymers (PI, NBR) at 10 mg/mL.
• A mixture of form 1 and form 2 was obtained using HPMC, dextran, and gelatin at 10 mg/mL, and at 0.5 mg/mL with certain polymers.
• The study successfully identified conditions for crystallizing the metastable form 2, often in combination with form 1.

Conclusions:

• Polymer-induced heteronucleation is a viable strategy for controlling progesterone polymorphism.
• The use of polymeric devices shows promise for crystallizing the metastable and more soluble form 2 of progesterone.
• This approach could lead to improved pharmaceutical formulations and applications of progesterone.