Solid State Research

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 and shelf life can be radically influenced.

Our crystallization platform accommodates high-throughput salt screening studies using only minimal amounts of drug substance. Salt screening is used for both early phase salt selection studies and broad patent protection.

The therapeutic effect of a drug substance is typically dependent on its chirality. Legislation as well as an increased understanding of the molecular interactions between small molecules and their biological targets have shown a rise in the number of single enantiomeric drugs being launched on the market.

Acquiring an enantiopure product from a racemic mixture is a challenge because enantiomers have identical physico-chemical properties.

Our conglomerate screening capabilities help to identify potential solid form candidates which enable efficient chiral resolution by crystallization. In combination with solution-phase racemization, the target chiral solid form can be isolated with an unprecedented high yield.

Our high-throughput salt-screening services furthermore enable the identification of diastereomeric salt forms of a drug substance which allow efficient chiral resolution through crystallization.

The ability of a drug substance to form a co-crystal depends on a range of variables, with the most important being the number of H-bonding donors or acceptors and its steric properties. By systematically exploring the combination of relevant variables, we increase the chance of discovering a co-crystal with the desired properties.

Our in-depth crystallization expertise, rational design of experiments and proprietary high-throughput technologies, mean we can successfully identify and characterize co-crystals.

Regulators require that companies fully characterize the polymorphs of their drug substances and checked for polymorph interconversions that can impact therapeutic performance.

Due to the unpredictable behavior of polymorphs and their different physicochemical properties, companies also have to demonstrate consistency in manufacturing between batches of the same product.

Our unique polymorph screening methodology enhances the understanding of the polymorphic behavior of drug candidates. The scope and size of studies range from small screens for the initial indication of polymorphism to large screens for intellectual property use.

Our polymorph screening services use proprietary high-throughput crystallization technology, with the capability to perform more than 1000 screening experiments using only a few grams of drug substance.

Using the amorphous form of a drug substance offers several advantages in terms of dissolution rate and solubility. However, reduced chemical stability, increased hygroscopicity and physical instability are the major drawbacks of using the amorphous phase in the final drug product. This creates the need to stabilise the amorphous phase of the drug substance in a polymer matrix, e.q. an amorphous solid dispersion.

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. We have developed high-throughput solid dispersion screening technology to find the optimal combination of these factors.

Our comprehensive screening programs are designed to obtain the whole range of solid forms of drug substances (polymorphs – including solvates and hydrates, salts, co-crystals and amorphous solid dispersions).

By combining experimental design expertise, high- and medium-throughput screening and chemometric analysis with state-of-the-art analytical techniques our screens provide the best chance of success.

Intellectual Property (IP) of the relevant solid forms is vital to defend innovator patents. Our thorough screening techniques ensure identification and characterization of the solid form landscape of a drug substance, as well as detection of potential patent infringement.

Additionally, with over a decade of experience in drafting patents for drug substance solid forms we help customers ensure their molecules are protected in the most effective manner.

In cases of substandard and counterfeit medicines, investigation of the solid form of the drug substance, or any of the ingredients of the formulation, is essential and may reveal differences in quality or even violation of IP.

We use our analytical equipment to characterize the solid-state of the drug substance or excipients of both the genuine and suspicious products in order to pinpoint the differences.