We deliver the solid state services, tools, and technologies needed to support your drug substance development programme and deliver an API with the desired attributes to enhance material efficiency and therapeutic success.
Solid state chemistry services at Sterling
Identifying the optimal solid form of your API is a critical step in its journey to market. Your drug substance’s solid form directly impacts its solubility, bioavailability and, through clinical evaluation, therapeutic efficacy. In addition, selecting the right solid form early on enables more efficient and cost-effective development and manufacturing processes, mitigating the risk of unanticipated challenges. At Sterling, our comprehensive solid state science services enable us to help you bring the ideal form of your API through manufacturing and ultimately to the market. ... Read more
Our team’s solid state expertise supports extensive solid form investigations and robust crystallisation development programmes. By fully understanding your project requirements and working closely with you, we can help discover and select the optimal target solid form and ensure its suitability for manufacture and commercialisation.
Not only are our solid state services available as part of an integrated chemical development programme, but we can also provide standalone solid form investigations and crystallisation development packages tailored for your specific requirements.Read less
Our Material Science Centre is equipped to support your solid state requirements.
Our solid state scientists have a range of experience to support our customers’ API solid state investigation and development requirements.
Comprehensive solid form solutions:
Our solid state chemistry team is capable of identifying the ideal version of your API at any stage through four interconnected areas of investigation: salt/cocrystal selection, polymorph investigation, pre-formulation evaluation and crystallisation development, aided by a range of analytical techniques.
Learn more about our solid state capabilities and analytical techniques:
Salt and cocrystal screening of your API enables us to manipulate your API’s solubility, dissolution profile, and physico-chemical properties. We utilise various investigations to discover salts or cocrystal versions of your API that deliver enhanced solubility and bioavailability. These investigations not only aid in early development and purity control; they can also be utilised to generate intellectual property for your API and alter the properties and drug product dosage of your API without changing the pharmacologically active moiety.
The API characteristics which can be modulated via salt/cocrystal versions and advance your API are:
- Solubility and dissolution profile, which can influence bioavailability
- Chemical purity
- Physico-chemical – crystallinity, thermal properties, hygroscopicity, particle size, polymorphism, density, colour, flow, filterability, drying and taste
Through polymorph screening, we discover your API’s potential to take on different solid forms. As with salt and cocrystal screening, screening for polymorphs can enable us to identify key properties of your API, that can have an impact upon efficacy, stability and impurity control.
Identifying the propensity of an API to polymorphism early on enables us to recommend the ideal API target, via form hierarchy, that can deliver the appropriate efficacy and stability. It also helps to proactively overcome challenges in the long run to avoid added costs and extended timelines. As with salt screening, we can tailor an expanded polymorphism investigation to generate intellectual property for your API.
Polymorphic forms of your API can vary characteristics such as:
- Solubility – which can influence bioavailability
- Physico-chemical – thermal properties, hygroscopicity, density, colour, flow, filterability, drying
If multiple potential solid forms are identified as possible candidates through salt, cocrystal and polymorph investigations, pre-formulation evaluation enables us to assess the API versions suitability under various conditions. Understanding how different solid form variations respond to external factors enables us to identify which candidate is best suited for your API to move forward. We consider parameters such as solubility and stability in aqueous and biorelevant buffers, form and chemical stability through stability investigations and the physical resilience of the solid to mechanical stresses. Salt/cocrystal and polymorphism investigations can afford multiple solid form version options for progression and is a balance of risk with the cost of advancing a version which might be unsuitable.
Pre-formulation evaluation can aid the selection via assessing and prioritising the various solid forms by employing the following investigations:
- Solubility and form/chemical stability in relevant aqueous media including biorelevant media and liquid formulation media, or other excipients
- Chemical and solid form stability to conditional storage under accelerated stability conditions
- Impact of mechanical forces such as compression and particle attrition
Initial evaluations enable us to select the best solid form to move forward to crystallisation development, progressing to production of your API solid. Crystallisation enables us to control purity levels and affords the target API version with appropriate particle habit and size distribution.
Crystallisation development is among the most important and most challenging aspects of API development, as it must address numerous physical characteristics of the API and ensure the desired solid form version can be achieved repeatedly. Crystallisation impacts numerous key physical properties that are integral to supporting smooth operations moving forward. An API’s material characteristics can have implications for filtration and drying, secondary processing, and drug product manufacture.
We work closely with our customers to understand and resolve their crystallisation challenges. Our crystallisation development services enable us to deliver your optimal solid form in a repeatable and scalable way. When tailoring your crystallisation development programme, we consider cost and time without compromising product quality, as well as health, safety and environment.
Crystal growth is a function of compound solution saturation and seeding; Crystallisation development is driven by understanding the solubility profile and metastable zone width of your API in solution and be predictable with ‘seeding’.Crystallisation can control and afford the desired particle attributes of your API:
- Chemical purity and impurity levels
- Solid form version such as polymorphic form, hydrate, solvate, salt or cocrystal
- Particle morphology, size distribution, dissolution characteristics
Process factors which can affect API crystal growth are temperature, particle size, impurities, mass transfer, heat transfer, agitation and boundary layer effects.
The particle morphology of your API is important for flowability, filterability, compaction and particle size, which are influenced by nucleation, crystal growth rates, solvents and supersaturation.
Physical modification of bulk API particle properties may be employed to improve drug product manufacture or enhance performance.
Particle size reduction is an approach to improve the solubility/bioavailability of BCS/DCS Class IV APIs that demonstrate both low solubility and low permeability. Bulk API particle manipulation (micronising and milling) can normalise particle size distribution (PSD) variations between API batches required for formulation manufacture. The mode of drug product administration can direct the required particle size of the API.
Consequently, API particle characteristics which can be altered by particle size reduction such as shape, size, size distribution, adhesiveness, density, flowability, wettability and compaction are important during drug product manufacture.
Particle size reduction can modify the solid form version of the API and other characteristics; consequently, the most suitable solid form version must be selected for further development and progression.
A range of analytical techniques support our solid state services, enabling us to identify your API’s preferred characteristics:
- X-Ray Powder Diffraction (XRPD)
- Differential Scanning Calorimetry (DSC)
- ThermoGravimetric Analysis (TGA)
- Dynamic Vapour Sorption (DVS)
- Infra-red Spectroscopy (FTIR)
- Ultraviolet Spectroscopy (UV)
- Solution NMR Spectroscopy (NMR)
- Ion Chromatography (IC)
- Optical Microscopy
- Hot Stage Microscopy (HSM)
- Particle Size Distribution (PSD)
- High Pressure Liquid Chromatography (HPLC)
- Gas Chromatography (GC)
- Water content by Karl Fischer titration
- Chemical structure solution by single crystal x-ray crystallography (outsourced)
- Chemical structure investigation by solid state NMR spectroscopy (outsourced)
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