By understanding the intrinsic properties of the drug substance, we are able to develop prototype formulations that improve the biological performance of a drug candidate and maximise the chances of success in preclinical studies.

Through our in-house solid form analytical and preformulation team, we are able to support analytical requirements for IND applications and support early phase clinical studies. As a non-GMP facility we are able to work with maximum efficiency and flexibility to meet customer milestones.

Scouting studies for enabling formulation encompasses a wide range of screening methodologies and analytical techniques, depending on the intended administration route.

Services to support formulation

  • Solution based Forced Degradation studies including stability as a function of pH, temperature, oxidative stress and photostability using in-house HPLC/ UPLC generic or customer methods as appropriate. Knowing the potential degradation triggers for a compound helps us to design suitable formulations that prevent failure by protecting against known possible sources of degradation.
  • Stability studies on the drug substance to investigate the influence of temperature and humidity during storage – understanding the stability boundaries of your API is critical for understanding control measures needed during preparation, isolation and storage to ensure materials can be shipped, stored and packaged appropriately.
  • Early stability studies on solution based formulation prototypes to evaluate any possible changes in chemical purity and assess propensity for precipitation or solid form changes over time. Evaluating stability and tracking key impurities over time gives an idea of shelf-life and short term stability for early stage studies such as in-vitro tox. Even simple early stage formulations need to have some stability data which will feed into how prototypes may need to be handled and stored in clinical houses for use during these early stage in-vitro studies.
  • Excipient compatibility and surfactant screening work for poorly soluble APIs, including lipid based screening. If aqueous solubility is problematic the addition of excipients and surfactants both in solid and liquid dosage forms can help to improve properties such as stability, handleability and solubility. It is however also important to understand both the short and long term influence of these different components on the integrity of drug substance by monitoring for any adverse interactions such as changes in form or loss in chemical purity.
  • Comparison of performance for lead formulation prototypes. Once lead prototypes have been selected it’s important to evaluate their performance against one another to make recommendations to our clients on which prototypes demonstrate the greatest benefits in terms of stability and uplifts in solubility.

Through our in-house physicochemical and analytical services, and working collaboratively alongside the solid form team, we are able to drive informative and data led formulation development for the early stages of pharmaceutical development.

 

Case studies

Stability and compatibility study for the development of an anti-retroviral and contraceptive

In 2018, Veranova carried out stability and compatibility studies for the development of an anti-retroviral and contraceptive vaginal ring.

Problem:

Due to the target region and the limited availability of medical supplies and refrigerated storage conditions in this particular area, the stability of both APIs was critical at elevated temperatures. Longevity and stability of release rate from the polymer blends was also key to ensure that dosing/use could be prolonged over a 3 month period.

Previous data had been collected on both dapivirine and darunavir, but not in combination with one another, so interaction of both APIs with the polymer matrices was also of interest.

Scope of work carried out at Veranova:

  • HPLC method compatibility for analysis of both APIs simultaneously
    • Assay and % recovery
    • Purity profiling
    • Dissolution to confirm stable release rate over time
  • Storage of the supplied polymer discs at 3 different conditions
  • XRPD and DSC method development for analysis of the discs at each time point

Outcome:

The study showed that both APIs remained stable over the 3 month period investigated, but some loss in purity of the darunavir API was observed during sample preparation, when heat was applied to melt the polymer blends. A recommendation was made for a particular blend of polymer (silica based) that showed little or no variation even at extreme temperatures (70 °C).

Development of an ophthalmic formulation

In 2018, Veranova carried out solubility studies on a topical eye drop for the teratment of wAMD (wet age-related macular degeneration).

Problem

The API intended for topical use as an eye drop exhibited poor aqueous solubility. There was no stability information available prior to project start.

Scope of work carried out at Veranova:

  • Candidate selection via batch characterization and forced degradation studies (photo-stability, stability as a function of pH and temperature, oxidative stress)
  • Excipient and surfactant screening/compatibility testing
  • 2 x prototype formulation development
  • 2 x informal 6 week stability for selection of lead prototype
  • 6 month stability study to support IND application

Outcome:

A lead candidate was selected. The prototype formulation was developed in-house with the stability study extended to 18 months. The data was shared with the client and the asset was bought by investor.

Improving aqueous stability of an ophthalmic treatment for dry eye

Problem

In 2016, an API with poor aqueous solubility was intended for topical use as an eye drop for the treatment of dry eye. There was limited stability information during the pre-IND application stages.

Scope of work carried out at Veranova:

  • Full characterization
  • Forced degradation studies (photo-stability, stability as a function of pH and temperature)
  • Excipient and surfactant screening/compatibility testing
  • Formulation development
  • Scale up to 1L for proof of concept prior to manufacture (using the Optimax)
  • 6 month stability study extended to 12 M to provide data to support IND application

Outcome:

We successfully formulated a stable prototype, overcoming concentration issues by using surfactants and pH adjustment. Bacterial growth was observed in the original storage samples so a repeat preparation was made using filtration as a sterilisation method in addition to autoclaving glassware. Stability testing was conducted in off-the-shelf eye dropper bottles.

Formulation is currently in Phase 2 clinical trials and client has returned for more work on a higher concentration formulation due to success far.

Solid Form Sciences

Amorphous Solid Dispersion

Chiral Resolution and Confirmation

Crystallization development

Enabling Formulation

Particle Size Modification

Physicochemical & Solid Form Profiling

Salt, Cocrystal & Polymorph Screening

Structure Confirmation

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