Understanding and controlling the physical properties of active pharmaceutical ingredients is of critical importance, for many reasons. First, the physical attributes of an API formulated as a solid dosage form will impact its bioavailability, and consequently its efficacy. For compounds that can exist in multiple crystalline forms with small energy differences, form interconversion during standard manufacturing, processing and storage poses serious problems that can lead to significant delays in advancing the drug toward regulatory approval. Issues of late appearing polymorphs for marketed drugs have clearly devastating economical consequences, as many recent cases demonstrate. Finally, intellectual property coverage to protect the innovator from generic competition and the extension of the drug life cycle through the development of alternative viable physical forms are all important considerations making it imperative to tackle the definition and control of the best, developable form early on during the drug development process.
OKAPI Chemtech offers modular screening and development services that can be entirely tailored to your particular needs, including the following:
Salt screening and selection:
The study is undertaken on ionizable APIs to identify the most desirable salt form with improved properties such as solubility, crystallinity, thermal stability, hygroscopicity, etc. Particular attention is paid to use preferably solvents that are considered relatively safe (based on ICH classification) and pharmaceutically acceptable counterions
The extent of the screen is determined by your development objectives. We offer:
- a preliminary screen: for the identification of polymorphs using a limited supply of API, without extensive characterization (for example the assessment of the thermodynamic solubility and relative stability of the various polymorphs and other physical forms identified during the screen will require the availability of enough material for a modest scale-up)
- a basic or standard screen: which includes a full characterization of the observed polymorphs or pseudo-polymorphs (hydrates, solvates) and
- a comprehensive screen: using a larger selection of solvents and experimental techniques, usually for the purpose of exploring and covering the IP landscape
Our screening protocols use standard approaches such as slurrying, grinding or solvent drop grinding techniques. Some of these methodologies, such as grinding procedures, may be difficult to scale up in a reproducible manner. Upon your request, OKAPI will further evaluate potentially scalable procedures following the initial screen.