Solid form screen: salt, polymorph, cocrystal & amorphous solid dispersions
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Solid form screening, including salt, polymorph, cocrystal and amorphous solid dispersions, is vitial for successful pharmaceutical development. With an increase in the size and complexity of the molecules that enter into drug development, companies face a larger number of compounds that are either poorly soluble, difficult to crystallize or problematic with respect to desired physical chemical properties hindering successful drug development. Crystallics has an extensive track record in executing solid state research studies and its research team has a broad expertise in identifying new crystal forms as well as in solving problems related to polymorphism and crystallization.

Salt screening

Physicochemical properties of drug substances, such as solubility, dissolution rate, and physicochemical stability can be altered significantly by salt formation. Consequently, important properties of the drug product such as bioavailability or shelve life can be radically influenced. Crystallics' technology platform for crystallization screening accommodates salt screening studies using only minimal amounts of drug substance while still performing a large number of experiments. High-throughput salt screening is used for both early phase salt selection studies and broad patent protection.

Cocrystal screening

Cocrystals provide additional opportunities to alter the physicochemical properties of the drug substance or to crystallize compounds that fail to do so by applying more conventional approaches. For non-ionizable APIs, cocrystallization is the alternative to salt formation for altering the physicochemical properties.

The ability of a drug substance to form a cocrystal depends on a range of variables, with the most important being the number of H-bonding donors or acceptors and its sterical properties. Crucial factors in obtaining cocrystals include the type and hydrogen bonding possibilities of co-former, the drug substance, co-former ratio, the solvents, the temperature, the pressure and the crystallization technique. By systematically exploring the combination of relevant variables Crystallics increases the chance of discovering a cocrystal with the desired properties. Crystallics has built a successful track record in identifying and characterizing cocrystals by applying a unique combination of in-depth crystallization expertise, rational design of experiments and proprietary high-throughput technologies for experimentation and analysis.

Polymorph screening

The pharmaceutical industry is often confronted with the phenomenon of multiple polymorphs of the same crystalline chemical entity. Polymorphism is often characterized as the ability of a drug substance to exist as two or more crystalline phases that have different arrangements and/or conformations of the molecules in the crystal lattices giving the crystals different physicochemical properties. The ability to be able to manufacture the selected polymorphic form reliably is a key factor in determining the success of the drug product.

Regulatory agencies worldwide require that, as part of any significant filing, a company has to demonstrate that it has made a reasonable effort to identify the polymorphs of their drug substance and has checked for polymorph interconversions. Due to the unpredictable behaviour of polymorphs and their respective differences in physicochemical properties, companies also have to demonstrate consistency in manufacturing between batches of the same product. Proper understanding of the polymorph landscape and nature of the polymorphs will contribute to manufacturing consistency.

Crystallics’ unique polymorph screening methodology enhances understanding of the polymorphic behavior of drug candidates. The scope and size of those studies vary depending on the development stage of the drug candidate and can vary from a small size screen for initial indication of polymorphism to a large size screen for intellectual property use. Crystallics provides high-throughput polymorph screening services, when necessary, using its proprietary high-throughput crystallization technology, and is capable of performing well over 1000 screening experiments with only a few grams of the drug substance. Each screening project is specifically designed to meet all of the customer's objectives.

Amorphous solid dispersion screening

Using the amorphous form of a drug substance offers several advantages with respect to dissolution rate and solubility of the substance. However, reduced chemical stability, increased hygroscopicity and, most important, physical instability are the major drawbacks of using the amorphous phase in the final drug product. These drawbacks can be overcome by stabilizing the amorphous phase of the API in a polymer matrix, e.q. an amorphous solid dispersion. Amorphous phases dissolve more rapidly than crystalline forms, and can significantly increase bioavailability of poorly water soluble drugs substances. However, the use of amorphous materials requires confidence that crystallization will not occur during the product lifespan. For a material that has never been obtained in a crystalline form, focus should be put on attempting to crystallize it. Crystallics has extensive experience of obtaining crystalline phases from amorphous materials.

Dispersions of a drug substance onto a polymeric matrix has received increased attention in recent years. A successful dispersion results in an amorphous solid material and will show improved dissolution rates and higher apparent solubility characteristics, as well as, sufficient resistance to chemical degradation and should be physically stable e.q. sufficient high glass transition temperature avoiding crystallization of the API. A variety of factors contribute to the formation of a suitable Amorphous Solid Dispersion (ASD), including the nature of the polymer, the drug polymer ratio, the impact of surfactants and the solvent used in the process. Crystallics has developed high-throughput solid dispersion screening technology in order to find the optimal combination of these factors.

Comprehensive screening

Increased costs for drug development, weak product pipelines and particularly, increased competition, are forcing the pharmaceutical industry to explore the true potential of existing molecules in order to maintain or extend patent protection. The quest to stretch a molecule's patent protected life has become at least as important as the discovery and development of new drug candidates. Lifecycle management is a strategic exercise for the pharmaceutical industry for which solid state research provides new insights and techniques.

Crystallics' comprehensive screening programs are designed to obtain the whole range of solid forms of a drug substance (polymorphs - including solvates and hydrates, salts, cocrystals and amorphous solid dispersions). Through a sequence of experimental design, high- and medium-throughput screening and chemometric analysis, and by combining state-of-the-art analytical techniques with experimental work at different scales, the screens are designed with the highest level of experimental diversity thereby providing the best chance of success.

High potent substances

Crystallics is one of the few companies worldwide that is able to work with high potent substances. The set up of our laboratory is in line with international and national regulatory authorities and we hold the necessary certificates to work on high potent substances. Crystallics can perform all solid state experiments required to bring your project with high potent drugs to the next stage.

Controlled substances

Crystallics is also one of the few companies worldwide that hold the necessary certification to work with controlled substances. The permits allow us to import controlled substances and work with them in our laboratories, performing all solid state experiments required to bring your project to the next stage.