API Optimisation

Our API-Optimisation support picks up from the moment the Chem Dev synthesis team deliver the API powder to the Pharm Dev team. At that point, the need is to understand the material being worked with, and most importantly, what is the optimal form possible.

Full Service Characterisation Service, which includes:

NMR, XRPD, DSC, TGA, DVS, FTIR, Hot Stage and Polarised Microscopy, Aqueous Solubility, also pH and a simple HPLC analysis to begin to understand purity. This initial characterisation data provides a benchmark to begin to understand the material “as is”, and determine areas where properties, if any, need optimising. It also allows you to track the impact of changes to the API. All of this work is carried out by our analytical scientists within GMP-controlled laboratories.

Where a molecule has an ionisable centre the development team may want to perform a Salt Screen at this stage.

Salt screening is a critical part of drug development programs where molecules have ionisable centres, both as part of an IP review and also to understand the benefits (or otherwise) associated with using different salt forms.

hot-stage-microscope

We have developed a robust screening technique that is capable of screening acid and base counterions in a focused manner which optimises the experiments performed on the API so as to select the most appropriate salt. Our screen looks to produce the salt forms and to quickly characterise their performance (solubility, melting point, crystallinity and structure). The goal from here is to provide a short list of forms for scale-up and full characterisation. Salt screening work is carried out using in-house expertise and within GMP controlled laboratories and techniques for optimum quality of data.

We can also provide a Polymorph Screen either as a standalone project or in conjunction with a salt screen to minimise time and cost of screens.

Understanding the structural landscape of an API is of critical importance as polymorphs may have significantly different physical properties (e.g. melting point, solubility, stability dissolution etc., particle shape). These physical differences can impact manufacture, efficacy, stability and bioavailability of the final product. Furthermore, understanding the polymorphic landscape is of commercial importance in protecting Intellectual Property as well as being a requirement for some regulatory bodies.

The primary screening goal is typically to identify the polymorph with the most suitable physical/ chemical properties based on your needs which can be prepared under expected processing conditions. Our screens are carefully structured to meet your team’s goal. In addition, this work also provides an opportunity to assess the solvent solubility of the compound in a range of carefully selected solvents used in the screen.

In addition to the standard screening work which can be carried out, we also offer a crystallisation service which aims to generate crystals of sufficient quality for single crystal analysis for compound identification and (if appropriate) publication or of a sufficient quality to allow further evaluation.

The polymorph screening work is carried out by our teams on site using a range of methods to ensure the optimal Form is identified. This work is supported by our wide range of in-house analytical equipment, including XRPD, FTIR, DSC, TGA, Polarised Light Microscopy, DVS, Raman, HPLC and Karl Fischer, as well as many other techniques.

Crystallisation Optimisation

Chem Dev teams are always under pressure. Often the method used for the initial crystallisation is non-optimised which can lead to costly processes when the compounds are scaled-up for manufacture. We can look at an entire process to determine the optimum conditions for any crystallisation step during a synthetic route to give results within specifications and of the highest yield and purity possible.

Again our highly trained on-site team with access to essential analytical methods are able to carry out this work efficiently and to strengthen your position to drive the project forward.

The focus here moves from API to a dose form that can be trialled in pre-clinical studies.
Salt screening is an important part of any drug development programme, both as part of an IP review and also to understand the benefits (or otherwise) associated with using different salt forms.
Polymorphism in pharmaceuticals may be defined as the ability of a drug substance to exist in two or more crystalline forms.
Often, early stage approaches to solubilising a drug substance (for example using DMSO) are not appropriate for a dose formulation that needs to be suitable for pre-clinical and clinical studies.