Solid Form Screening & Selection

We tailor our screens function of drug substance physchem properties, available time frame, and customer budget. Our main goal is to create value for our customers.
All our screening programs are supported by an analytical package that includes:

  • X-Ray Powder Diffraction (XRPD)
  • Differential Scanning Calorimetry (DSC standalone)
  • Thermo-Gravimetric Analysis coupled with DSC (TGA/DSC)
  • Fourier Transformed Infrared (FT-IR) and Raman Spectroscopy
  • High Performance Liquid Chromatography (HPLC)
  • Polarized Light Microscopy (PLM)
  • Nuclear Magnetic Resonance (NMR), and many others

All these techniques are employed to select the most optimum solid form of the drug substance to be considered for development.

Our screening programs can also be tailored to include solid state and solution stability tests (e.g., different accelerated and long-term storage conditions, photostability, pure water or basic and acidic conditions, oxidative conditions etc.). The purpose of stability assessment involves the identification of the suitable working conditions in which the compound is stable or partially/totally degraded. The results obtained during this stage are essential in choosing the
experimental conditions for the next stages of screening programs. The progress and nature of degradation and/or transformation of samples are assessed by visual inspection and HPLC. In case of solids resulted as precipitate from solution or behave as slurries, the form changes are evaluated by XRPD. If any transformation is noticed, other analyses can support interpretation (TGA/DSC or DSC standalone).

Polymorph Screening

SARA Pharm Solutions offers polymorph screening programs that aim to identify a stable crystalline form of the API. Tailored to customer needs, our designs include a considerable high number of crystallization experiments and target to deliver a robust crystallization process that can be easily transferred to larger scale.
The bio-pharmaceutical properties of each crystalline form are established using several advanced solid-state characterization techniques available in our labs. The benefits of using our approach are:

  • aqueous and organic solvent solubility assessment
  • polymorph screens are rationally design
  • all crystallization methods are tailored to the phys-chem properties of the drug under study
  • HT-XRPD is used to identify and locate (new) crystalline forms
  • number of experiments are tailored based on the available amount of drug substance
  •  performing process optimization of the crystallization scaling-up process
  • expert understanding of generated data is available

A new polymorph of your API with enhanced bio-pharmaceutical properties may be considered to strengthen the Intellectual Property (IP) portfolio of your company.

Salt Screening

We offer tailored salt screening and selection programs focused on meeting the customer expectations and needs. If no stable or more soluble new crystalline form is identified during the polymorph screening, the salt formation screening is the next step to obtain the improvement of API’s physico-chemical properties. Considering the salt formation process we screen a high number of counter ions selected based on:

  • experimental or predicted pKa values of the free form (API)
  • market precedence of counter ions (“Orange Book”)
  • known toxicology data of each counter ion and solvent system (ICH guideline)
  • aqueous and organic solvent solubility assessment
  • all acido-basic crystallization methods are tailored to the physico-chemical properties of the drug under study
  • HT-XRPD is used to identify and locate (new) crystalline salt forms
  • number of experiments are tailored based on the available amount of drug substance
  • physico-chemical stability (ICH guidelines) evaluation of new salt forms
  • as part of salt screening, if the customer is interested to know the API affinity in water (or aqueous systems) or in organic solvent(s), the logP/logD determination gives an idea about the drug distribution in hydrophilic and lipophilic solvent
  • performing process optimization of the salt formation scaling-up process
  • expert understanding of generated data is available

The aim is to locate a high number of stable crystalline acceptable salts that meet the pharmaceutical property requirements. Once evaluated, the most acceptable salt forms are scaled-up and then fully characterized. Such an investigation is carried out for all salt forms, allowing SARA Pharm Solutions’s scientists to rank the salt forms with respect to their crystallinity, stability, solubility, purity, reproducibility, etc.
A salt form with enhanced bio-pharmaceutical properties may be considered to strengthen the Intellectual Property (IP) portfolio of your company.

Co-crystal Screening

Co-crystallization is a crystal-engineering technique employed in case of non-ionizable organic molecules that are unable to form salts. Also, the co-crystallization is used for improving the stability of an API if a polymorph or a salt previous identified does not meet this requirement. The aim of such a process is to obtain a new solid form with acceptable bio-pharmaceutical properties. Our approach in co-crystallization is custom made and offers several advantages such as:

  • co-crystallize ability is theoretically (via modeling) and experimentally assessed
  • aqueous and organic solvent solubility assessment
  • based on the physico-chemical properties of the drug under study, the solid state or slurry/solution co-crystallization techniques such as dry- and solvent-drop grinding, slurry, slow evaporation, sonication, cooling co-crystallization etc.
  • performing process optimization of the co-crystallization scaling-up process
  • we investigate co-crystals physchem stability (ICH guidelines) evaluation of co-crystals
  • expert understanding of generated data is available

The identification of most suitable co-crystal form is supported by thermal stability analysis, single-crystal data analysis etc. A co-crystal form with enhanced physchem properties may be considered to strengthen your Intellectual Property (IP) portfolio.

Amorphous Solid Dispersions Screening

Amorphous phase plays a key role in the solid-state pharmaceuticals field. This is due its greater solubility in comparison to any crystalline form of the same API. Our scientists focus on the following aspects:

  • preparation of amorphous phases using solid and solution-based methods
  • characterization and quantification of the amorphous phases
  • stabilization of amorphous phase (e.g., via amorphous solid dispersions, ASDs)

Advantages of using our approach:

  • quick and easy production of amorphous phase
  • full characterization of amorphous phase and ASDs
  • rational design of ASD screen
  • ICH guidelines stability studies for Am phase
  • expert understanding of generated data is available

The experience of our scientists in the field of amorphous phase stabilization ensures the success of your research program with us.