Overview

Overview

Physical form optimization

 

 

Early characterization of Discovery bulks often helps identifying critical milestones to be included into the drug candidate preclinical development plan. Drugabilis regularly performs those measurements on minute bulk amounts.

Thanks to our well-equipped characterization platform, Drugabilis can work on:

  •  Crystallinity assessment
  •  Thermal profile assessment
  •  Hygroscopicity measurement
  •  Hot-stage microscopic observations
  •  Hydrate and solvate identification
  • API physical form stability evaluation under stress conditions
  • Relative stability of polymorphs
  • Crystallization of amorphous API
  • Crystallization process support: find a suitable medium/conditions to produce the selected form, find a suitable medium to purify
  • Set up and validation of polymorphs quantification
  • Physical caracterizations to support freeze drying process (glass transition temperature determination...)


Specific characterization issues related to formulation studies, physical compatibility between drug and excipients, API physical form change upon scale-up or synthetic route modification, proprietary drug delivery technologies and others should be raised to us. They will give Drugabilis the opportunity to design, every time possible, fast and adapted answers.

Salt selection

Salt selection

Salt selection

 

Salt selection is highly critical in the overall development process of a given active pharmaceutical ingredient. Frequent reasons for initiating a salt selection study are:

  • Improvement of poor physical properties
  • Solubility, dissolution and related bioavailability enhancement
  • Chemical degradation management
  • Process chemistry reasons such as purification or crystallization

Drugabilis will help you identify when to initiate efforts in a salt selection process. Thanks to our micro-scale screening methodology and characterization capabilities, we will then help you answer two main questions:

  • What counter-ions form crystals when associated to my API?
  • Which of the possible salts is likely to be the most suitable?

Drugabilis salt selection program will include:

  • Suitable counter-ion selection based on the drug delivery route, the study objectives and the API profile
  • Micro-scale salt screening tests
  • Hit-scale up to produce analytical samples for further characterization
  • Full characterization of the analytical samples
  • Comparison of the resulting “salt-candidates” and the parent compound properties according to the specific objectives of the study

Polymorphism

Polymorphism

Polymorphism

 

Early understanding the polymorphism profile of an active pharmaceutical ingredient (API) is a critical issue, not only because of patent-related issues, but also because a company can lose very significant time and money initiating its development with a form that is not the most stable one.
Drugabilis, has developed a systematic small-scale polymorphism screening methodology to quickly address the question: “Are we currently developing the most appropriate form of our API?”
Drugabilis polymorphism step-by-step program would include:

  • A micro-crystallization screening with API samples to maximize the chances to generate polymorphs, hydrates or solvates.
  • A comprehensive characterization of the generated forms by a number of techniques including optical microscopy, hot-stage microscopy, chromatography, Raman microscopy, thermo gravimetric analysis coupled to infrared analysis, differential scanning calorimetry and X-ray diffraction.


After a few weeks and with less than 1g of compound, Drugabilis guaranties a full polymorphism overview of your API, knowing how many crystalline forms - hydrates, solvates or true polymorphs – exist.

  • Drugabilis will then determine which form you should select for development, based on ad hoc physicochemical characterizations.
  • Based on the above studies, Drugabilis will also develop methods for assessing polymorphism purity in drug substances or drug products.
  • Drugabilis will support process chemistry in defining suitable crystallisation conditions to produce the desired crystalline form

Co-crystal screening

Co-crystal screening

Co-crystal screening

 

Oral absorption of BCS class II drugs is solubility limited. If the compound of interest is not ionizable, it is not possible to improve its solubility by making a salt. Furthermore, techniques like particles size reduction would improve dissolution rate but will not change the maximal concentration achievable in a solution.


As a relatively new response to this absorption issue, co-crystal strategy is a way to significantly increase compound soluble fraction and therefore potentially oral absorption.

 

Drugabilis co-crystal screening includes

 

  •  Choice of a list of ligands (more than 50 ligands are available)
  • In house screening methodology designed to favor the formation of co-crystals from compound-ligands mixtures
  • Identification of the couples compound-ligands that co-crystallizes
  • Characterization of the co-crystals: physical and physico-chemical properties are investigated thanks to Drugabilis expertise in both solid state and preformulation issues
  • Prioritization of the identified co-crystals