Crysforma - Scientific and Technological Support for Pharmaceutical Solid State Development

Crysforma is a technology transfer unit, belonging to the Institute of Chemical Research of Catalonia (ICIQ). We provide services for the discovery, analysis and scale-up of polymorphs, salts and co-crystals of active pharmaceuticals ingredients or intermediates. Crysforma has developed its own screening methodology based on the combination of several crystallization procedures.

Although we use high-throughput crystallization systems, all crystallizations are controlled by highly skilled scientists to maximize the scientific information drawn from each experiment.

Polymorphism – crystal form selection

Polymorphism, the ability of a chemical compound to crystallize in more than one crystalline phase, is a key issue in the pharmaceutical industry. Different polymorphs can have different physical and chemical properties, and thus can have an influence on the bioavailability of the pharmaceutical compound.

Moreover, the relative stabilities of the different polymorphs must be known in order to avoid unwanted polymorph transformations during production of the active pharmaceutical ingredient or the final pharmaceutical compound.

Type of studies:

• Initial or fast polymorphism screening for early stage candidates
• Comprehensive polymorphism study of a drug substance
• Characterization of the relative stability of the different polymorphic forms
• Determination of the most stable form under defined conditions
• Development of reliable procedures to prepare selected polymorphs
• Scale-up of the desired polymorph
• Development of analytical methods for polymorph quantification

Salt selection

Preparation of a salt is the classical strategy to optimize the solid state properties of an active pharmaceutical ingredient. Salt derivatives can improve crystallinity, solubility, hygroscopicity character and stability of a pharmaceutical compound, and are often chosen instead of the free acid or base.

Type of studies:

• Salt screening of pharmaceutical ingredients with selected counter ions
• Characterization of crystalline salts
• Development of reliable procedures to prepare selected salts
• Scale up of the selected salt
• Polymorphism study of the selected salt

Co-crystal development

The development of a co-crystal has become a novel strategy to improve the solid state properties of an API. A pharmaceutical co-crystal is a crystalline solid that incorporates two neutral molecules, one being an API and the other a co-crystal former.

Co-crystals are an alternative to salts when these do not have the appropriate solid state properties or cannot be formed due to the absence of ionization sites in the API.

Type of studies:

• Selection of co-crystal formers for a specific API
• Co-crystal screening of pharmaceutical active ingredients with selected co-crystal formers
• Characterization of pharmaceutical co-crystals
• Development of reliable procedures to prepare pharmaceutical co-crystals
• Scale up of pharmaceutical co-crystals 

Resolution of diastereomeric salts

The unit has adapted the salt screening methodology developed in the last years, to the resolution of chiral molecules with ionization sites through diastereomeric salt formation.

Type of studies:

• Crystallization screening to discover the optimal chiral resolution agent and crystallization solvent
• Scale-up of the resolution process

Crystallization of compounds

During the development of polymorphism, salt and co-crystal studies, the unit has acquired extensive experience in crystallization, which is used to successfully address the following issues:

• Crystallization of compounds that are difficult to crystallize or that are formerly only known as amorphous solids
• Development and scale-up of robust crystallization procedures
• Crystallizations oriented to the generation of single crystals for X-ray diffraction structure determination