Ricerca’s preformulation services can reduce time-to-market

At Ricerca, we believe that an adequate understanding of the properties of your drug substance can reduce problems in development, lower your development costs, and decrease development time. 

 

Preformulation is a branch of pharmaceutical sciences that investigates the physicochemical and biopharmaceutical properties of a drug substance. The goals of preformulation studies are to identify the best form of the drug substance, evaluate its physical properties, and learn about its stability. These studies are designed to identify and select the optimal solid state form of your API.

Salt Screen

Active pharmaceutical ingredients having ionization centers can form salts. Careful salt selection provides an opportunity to improve the characteristics of an API without changing its chemical identity. At Ricerca, salt screening begins with an in-silico treatment to assess the ability of the API to form salts. A salt library is designed that is tailored to the properties of the API with a focus on commercially viable and generally recognized as safe (GRAS) salt forms.  Robotic equipment is used to isolate samples of each salt form. The salt forms are evaluated for crystallinity, solubility, chemical stability, polymorphism, ease of crystallization, hygroscopicity, and bioavailability. Evaluation of these properties facilitates rational form selection, which can increase bioavailability, ease formulation and manufacturing, and improve the developability of an API. 

Polymorph Screen

Many pharmaceutical compounds are polymorphic (exist in more than one crystalline form).  Different polymorphs of an active pharmaceutical ingredient have different physical and chemical properties. These variations give rise to differences in solubility, stability, and bioavailability that can affect the safety and efficacy of new therapeutic agents. It is therefore important to evaluate each drug candidate for polymorphism.

Ricerca uses solvent and non-solvent based recrystallization methods to investigate polymorphism. Recrystallized samples produced by screening are analyzed by x-ray diffraction, thermal, optical, and spectroscopic methods. Newly discovered polymorphs are characterized and the energy relationships between the polymorphic forms are established. The characterization of each polymorphic form provides the necessary data for patent applications and permits the rational selection of the best polymorphic form for drug development.

Hydrates & Solvates

The chemical and physical properties of pharmaceutical solids depend on moisture (and solvent) content. Many compounds undergo changes in hydration state due to corresponding changes in ambient humidity. Because water vapor is present during virtually all facets of pharmaceutical manufacturing, a fundamental understanding of the relationship between water and the active ingredient is essential. A compound’s water sorption isotherm is generated by monitoring water content as the relative humidity is manipulated. The formation of hydrates (and solvates) is also investigated using solution-based techniques. At Ricerca, X-ray diffraction, thermal, and spectroscopic analyses are used to identify and characterize hydrates and solvates.

Co-crystal Screen

Co-crystals are crystalline solids containing two or more different molecules. A simple example is aspirin:saccharin. Like salts, co-crystals can be used to improve the physicochemical properties of the API that influence bioavailability, formulability, and manufacturability. Unlike salts, co-crystal formation is not limited to drug candidates having an ionization center, but is widely applicable to any type of active pharmaceutical ingredient. Co-crystal screening is performed by crystallizing a library of ‘guest’ molecules with the drug developmental candidate.  A co-crystal library is tailored to the molecular features of the API. The co-crystals isolated during screening are evaluated for crystallinity, thermal and spectroscopic properties, hygroscopicity, stability and solubility. 

Solubility

Ricerca collects solubility data using robotic liquid handling and microtiter plate readers. Both nephelometric and UV-based plate readers are available depending on the characteristics of the drug. The assays are compatible with organic solvents and aqueous pH profiles. Solubility screens can be stand-alone projects or done in conjunction with other solid state studies.

Crystallization Screen

Crystallization screening is aimed at producing a particular polymorph, salt, hydrate or solvate.  These studies can be used to improve yield or purity, control form and improve the degree of crystallinity. These studies are often implemented after a target form has been identified and selected using solid state screening. These studies can also be used to develop a process that is scalable, robust, and economically viable. 

Patent Support

Ricerca has discovered salts, polymorphs, hydrates, cocrystals, and crystallization processes that have led to patent applications. Projects aimed at producing patent quality data are available. The technical expertise of Ricerca’s scientific staff enables patent attorneys to develop robust claims as part of the patent application process. The study sponsors retain full ownership of all IP generated by Ricerca.