mSAS® strategies for enhancing the stability of pharmaceutical products

There are many factors which effect drug stability (e.g. temperature, light, pH, oxidation etc.) and both chemical and physical stability are vital to ensuring that therapeutics can be manufactured, stored, transported and administered to patients without a loss of efficacy or safety.

Some pharmaceutical processing technologies expose drug substances to damaging environments, such as high temperatures, mechanical stress and shear forces, which can lead to chemical and physical degradation, and leave them susceptible to further instability. Crystec’s mSAS® supercritical fluid (SCF) technology can be applied to a range of approaches to provide enhanced stability for small and large molecule therapeutics.

Highly crystalline material

mSAS® has the ability to produce highly crystalline material, and by tuning the precise crystallisation environment it is possible to screen for, and selectively generate, a preferred solid state form. This process allows strong selectivity of crystalline structure, typically resulting in material with very high solid-state purity. As a result, mSAS® material is generally more stable against solid-state transformation than material which has been produced through more conventional means, where localised areas of instability can seed conversion.

Low amorphous content

Amorphous content is a common feature in drug development and many pharmaceutical processing technologies are known to induce the formation of amorphous regions (e.g. through mechanical grinding or high temperature processing). Amorphous content can leave pharmaceutical products vulnerable to both physical and chemical degradation, often driven by uncontrolled crystallisation or increased affinity for moisture. Because mSAS® is a single step process combining crystal and particle engineering, highly crystalline powders can be generated with a targeted particle size, without the need for subsequent size reduction, resulting in inherently higher stability.

Eliminate residual solvent and impurities

Supercritical fluids have been used widely for extraction purposes for many decades. The unique and tuneable solubilisation properties of SCFs enable selective removal of certain components from complex mixtures. This provides a wide range of applications, from isolating active ingredients from plant extracts, to removing caffeine from coffee, and even in recycling components of electronic devices.

In mSAS® crystallisation, the SCF acts as a powerful anti-solvent, efficiently stripping solvent from an organic drug solution, while simultaneously extracting components with inherent solubility in the SCF. These properties can be exploited to precipitate pure drug particles with low levels of solvent and impurities, which could otherwise supress crystallisation and leave products susceptible to physical and chemical instability.

Further information about employing the solvent and impurity scavenging benefits mSAS® to optimising natural products can be found here.

Particles coated to protect against moisture

Where drug substances are hygroscopic, exhibiting a tendency to absorb moisture, eliminating exposure to water throughout the manufacture and supply chain can be a challenging but necessary step to avoid agglomeration and degradation. Despite innovation in packaging and the use of low humidity environments, formulation is often key to mitigating exposure and enabling commercialisation of such products.

Crystec routinely apply mSAS® technology to co-formulate Active Pharmaceutical Ingredients (APIs) with enhancing agents for a range of purposes (e.g. improving dissolution, absorption, dosing and stability). One such example includes the coformulation of a hygroscopic and strongly cohesive inhalation API with a regulatory approved excipient to protect against water absorption. Such an approach results in coated particles which remain stable, free flowing and aerosolisable throughout the lifetime of the product. This provides opportunities to reduce processing, packaging and supply costs, while ensuring delivery of a high quality and efficacious product to patients.

Ambient biotherapeutics

With an increasing number of biologically derived therapeutics (e.g. proteins, peptides) entering the market, a key barrier to development is ensuring adequate stability throughout manufacturing and supply chains. Distribution can often prove challenging due to low temperature storage conditions that are often required to prevent degradation. In many cases, water is removed from biotherapeutics in order to reduce cold chain requirements, but these processes often result in reduction in activity, reducing potency and potentially impacting safety.

Freeze drying (or lyophilisation) is frequently used to remove water and provide powders that can be reconstituted prior to administration. However, the shear forces and temperatures used in the system, as well as the long and complex cycle times, mean that fragile biomolecules are often damaged. mSAS® offers an attractive alternative, where low processing temperatures (close to body temperature), lack of shear forces and interfacial stresses, and short contact time, result in a relatively benign process whereby biomolecules can be precipitated with high levels of retained activity. mSAS® is a single step process that can incorporate additional agents where required, such as pH buffers and stabilising agents to further enhance stability post processing, and can also provide opportunities for alternative routes of delivery (e.g. dry powders for nasal or inhaled delivery).

Further information about mSAS® biomolecule processing can be found here.

If you would like to learn more about Crystec and how the mSAS® platform can be applied to enhance product stability, please get in touch directly at emily.bevis@crystecpharma.com

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