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Formulation Development

With over 30 years of experience formulating both large and small molecules for injection, you can rely on Curia. We can identify the quality attributes that impact the clinical performance and safety of formulations, analyze the manufacturability of dosage forms, and assess stability in primary packaging.

Pre-Formulation Research

Pre-formulation characterization studies generally include accelerated stability (stress) studies, stability-indicating analytical method development, and other physiochemical characterizations designed to pinpoint potential product candidate stability problems and enable formulation optimization. The goals of preliminary formulation research are varied, and give our scientists a baseline of data to progress forward and help make data-driven decisions:

  • Understand the significant physicochemical properties
  • Estimate a product’s stability when exposed to various common stresses
  • Develop stability-indicating assays for major degradation products
  • Decide upon a lyophilized or liquid formulation for initial clinical studies
  • Finalize a formulation development research protocol (matrix of buffer, pH, stabilizer, tonicity modifier; analytical methods; etc.)

Formulation Development

Developing a successful formulation is a critical step along the drug development journey, and Curia scientists have decades of experience to draw from, while also staying ahead of the curve with new technologies developed from internal research. Our skilled experts can develop liquid, lyophilized, and complex formulations.

Our formulation development studies are designed to meet or determine target product profile. We also offer proof of concept non-GMP laboratory batches supporting method validations, toxicology studies, regulatory filing, and shelf-life stability studies. 

Liquid Formulation

Sufficient stability information is required to achieve liquid formulations as many fragile pharmaceuticals have limited stability in liquid state. It is also important to understand that product stability in prefilled syringe may be different from the same formulation filled in vials.

Liquid formulations are the most common presentation for sterile injectables. As the most commercially viable option, Curia’s formulation teams have developed formulations for current commercial products, as well as for use in clinical trials.

Lyophilized Formulation

Lyophilized formulations are a common presentation choice, especially for molecules that benefit from the improved stability of the lyophilized state. To achieve robust lyophilized formulations, additional factors listed below need to be considered above and beyond storage stability.

  • Lyophilization cycle optimization
  • Elegant appearance of the lyophilized cake
  • Good stability during the freeze-drying process
  • Easy, rapid, and thorough reconstitution

Lyophilization Cycle Development

In order for us to develop the ideal lyophilization process, we must understand the following regarding your project:

  • Product integrity during lyophilization
  • Physical properties of formulations under frozen conditions, e.g., glass transition temperature or collapse temperature, re-crystallization or devitrification, and eutectic melting temperature of excipients in the unfrozen fraction
  • Desired final moisture content
  • Phase separation of key ingredients during freezing
  • Presence of key stabilizers, e.g., surfactant, water-replacing glass formers
  • Potential pH changes during freezing due to selective crystallization of buffer components
  • Vapor pressure of ice at desired product temperature

Complex Formulation

In addition to traditional liquid and lyophilized formulations, Curia also has a wealth of experience with more complex formulation approaches such as Co-formulation (two or more APIs), multi-dose formulations (include preservatives to prevent microbial growth), and alternative formulation approaches such as suspension, emulsion, liposomal, or nanoparticulate. For these latter alternative approaches, work packages are designed to support critical quality attribute requirements and to mitigate manufacturing challenges.

  • Particle size reduction / control
  • Encapsulation
  • Sterilization

Structural Analysis

We measure the secondary, tertiary, and quaternary structure of biologically active proteins. This includes:

  • Fourier Transformed Infrared Spectroscopy (FTIR)
  • Differential Scanning Calorimetry (DSC)
  • Fluorescence Spectroscopy

UPLC/HPLC Methods

We monitor various degradation of biological therapeutics, including:

  • Size-exclusion
  • Ion-exchange (cation-exchange, anion-exchange)
  • Reversed Phase
  • Hydrophobic Interaction
  • Various detectors: UV, Fluorescence, reflective index, evaporative light scattering, charged aerosol

Electrophoresis

This method separates impurities based on both charge and mass, such as:

  • Capillary Electrophoresis (CE)
  • Sodium dodecyl sulfate electrophoresis (SDS-PAGE)

Viscosity

Measurement for manufacturing process as well as injection through narrow bore needles.

  • Rheometer
  • Instron
  • M-VROC

Subvisible Particle Analysis

The potential immunogenicity of particles ranging from nanometer to micron sizes in biotherapeutics has been a growing area of discussion between regulators and industry. Both the USP and Ph.Eur. currently require biopharmaceutical products to quantify subvisible particles larger than 10 µm and 25 µm, respectively.

Due to the complex milieu of subvisible particles, sample preparation and the method of analysis can affect the accuracy of:

  • Particle Sizing
  • Particle Counting
  • Particle Classification

Consequently, multiple orthogonal techniques are strongly recommended for subvisible particle analysis. We offer multiple orthogonal techniques for subvisible particle characterization:

  • Flow Imaging Microscopy (MFI and Flowcam)
  • Dynamic Light scattering (Zetasizer, Wyatt)
  • HIAC Liquid Particle Counter
  • Light Obscuration

Other useful analytical methods include: 

  • Sub-ambient differential scanning calorimetry (characterization of frozen formulations)
  • Imaged capillary isoelectric focusing (iCIEF)
  • Karl Fisher
  • Osmometry
  • SoloVPE
  • GC
  • XRPD
  • DVS

Formulation Robustness Studies

Curia routinely performs a variety of formulation robustness studies to help support regulatory filings, develop manufacturing tolerances, and probe various stress factors common in pharmaceutical manufacturing, packaging, transportation, and storage. After a formulation matrix is identified, the stability of the drug product within the specification of each formulation parameter needs to be generated. In addition, the effect of various excursions from controlled stability study conditions on product stability have to be studied.

Examples of robustness studies include:

  • Formulation Robustness/DOE Ranging
  • Transportation Stress
  • Process Challenge or Excursions
  • Temperature Excursions

In-use Stability Studies

The stability of the drug product during intended application processes should be investigated, such as withdrawal from the primary container closure system, expulsion through delivery devices, mixing with diluents, adjuvants, etc.

Examples of In-use Stability Studies include:

  • Administration with disposable syringes
  • Administration with IV catheter with or without an in-line filter
  • Transfer devices
  • Diluent compatibility and dilution into IV infusion bags
  • Stability and integrity of multidose formulations over multiple container entries

Compatibility Studies

Since a drug product comes into contact with other materials, molecules, etc., the drug product’s stability and integrity needs to be demonstrated.

Examples of compatibility studies include:

  • Prefilled syringe compatibility
  • Extractables and leachables
  • Manufacturing process product contact material challenges
  • Primary fluid pathway
  • Pumping or mixing
  • Secondary container/closure systems
  • Excipient-drug compatibility
  • Drug-drug compatibility
  • Filter compatibility

Excelse Technology

Concentrating and efficiently delivering high-dose biologic medicine.

The Excelse Advantage

Our groundbreaking Excelse high-concentration formulation technology uses customized blends of amino acids to highly stabilize and concentrate delicate biotechnology medicines.

  • Permits concentration of intravenous liquid and lyophilized biologics into liquid subcutaneous injections
  • Significantly reduces viscosity
  • Allows for concentrations of up 300 mg/mL allowing 1 mL injections
  • Uses stabilizers that are non-active and FDA approved

Curia’s Discovery and Development Capabilities

Curia is able to collaborate and partner with you from preclinical to commercial.

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