Publication of Crystal Structure of Ritonavir Form IV and Thermodynamic Relationships between Ritonavir Polymorphs

Improved Pharma announces the publication of its research detailing the crystal structure of Ritonavir Form IV in Crystal Growth & Design. Using micro-electron diffraction (MicroED), the team successfully characterized the anhydrous polymorph and established its thermodynamic relationship to previously known Ritonavir forms, advancing the understanding of pharmaceutical polymorphism.

WEST LAFAYETTE, Ind., Jan. 27, 2026 /PRNewswire/ -- Improved Pharma is pleased to share that our research on the crystal structure of Ritonavir Form IV has been published in the highly reputable and peer-reviewed journal, Crystal Growth & Design. The article can be accessed here.

Ritonavir has long served as a defining example of the importance of polymorphism in pharmaceutical development. The 1998 recall of ritonavir upon the unexpected appearance of the more stable Form II polymorph remains a notorious case of disappearing polymorphs as the presence of Form II inhibited the ability to grow the original Form I. While Form III was observed in 2014, it was not characterized as a unique polymorph until 2022 when, coincidentally, a team at AbbVie and a team of scientists from Improved Pharma and Varda Space Industries independently discovered Form III via melt/cool crystallization. In this paper, we report the crystal structure of the anhydrous Form IV polymorph, determined using electron diffraction, and establish its thermodynamic relationship to Forms I, II, and III.

This work highlights the power of modern structural analysis. Because the Form IV crystallites were too small for traditional single-crystal X-ray diffraction, we utilized MicroED (micro-electron diffraction) to successfully solve the structure.

A special thank you to Pierre Le Maguerès and the team at Rigaku. Their partnership and the capabilities of the Rigaku XtaLAB Synergy-ED instrument were absolutely essential in overcoming the challenges posed by these nanocrystals.

It was also a pleasure to collaborate with our co-authors at Varda Space Industries on this project.

At Improved Pharma, we are proud to contribute to the fundamental understanding of complex solid-state relationships and to utilize advanced techniques like MicroED to solve persistent structural problems for our clients.

#SolidStateChemistry #Polymorphism #MicroED #DrugDevelopment #Crystallography #ImprovedPharma #Rigaku #VardaSpace

About Crystal Growth & Design
Crystal Growth & Design shares new scientific & engineering knowledge of crystal growth, crystal engineering, and application of crystalline materials.

About Improved Pharma
Improved Pharma is a research, consulting, and information company dedicated to improving pharmaceutical methods, formulations, and processes. Services include solid-state form studies, formulation design, synchrotron techniques, analytical testing, and expert consulting for the development and defense of intellectual property matters. The company was founded in 2006 by Stephen and Sarah Byrn, who also founded SSCI.

For more information about Improved Pharma's services, please visit https://improvedpharma.com/.

SOURCE Improved Pharma