Preparation and formulation of progesterone para-aminobenzoic acid co-crystals with improved dissolution and stability

Hibbard, T., Shankland, K. ORCID: https://orcid.org/0000-0001-6566-0155 and Al-Obaidi, H. ORCID: https://orcid.org/0000-0001-9735-0303 (2024) Preparation and formulation of progesterone para-aminobenzoic acid co-crystals with improved dissolution and stability. European Journal of Pharmaceutics and Biopharmaceutics, 196. 114202. ISSN 0939-6411 doi: 10.1016/j.ejpb.2024.114202

Abstract/Summary

The crystal structure of a new Progesterone (PROG) co-crystal with para-aminobenzoic acid (PABA) showing enhanced solution properties is reported. PROG-PABA co-crystal was first identified though an in silico coformer screening process using the CSD Co-crystal deign function, then confirmed through a solution evaporation crystallisation experiment. The resulting co-crystal was characterized using single crystal X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy. Liquid assisted grinding was selected as a suitable scale up method compared to spray drying and antisolvent methods due to minimal starting material phases in the final product. Following scale up, aqueous solubility, stability and dissolution measurements were carried out. PROG-PABA showed increased distinct aqueous solubility and dissolution compared to PROG starting material and was shown to be stable at 75 % relative humidity for 3 months. Tablets containing co-crystal were produced then compared to the Utrogestan® soft gel capsule formulation through a dissolution experiment. PROG-PABA tablets showed a substantial increase in dissolution over the course of the experiment with over 30× the amount of PROG dissolved at the 3-hour time point. This co-crystal shows positive implications for developing an improved oral PROG formulation.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/115220
Identification Number/DOI	10.1016/j.ejpb.2024.114202
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Optical Spectroscopy (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Thermal Analysis (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Xray (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Electron Microscopy Laboratory (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	Elsevier
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