Formulation Development

Pre-formulation

Pre-formulation development ranges from proof of concept to characterization. The pre-formulation process is crucial in order to provide practical insights to establish a clear and efficient formulation development plan that will accelerate the development of the drug product.

Proof of Concept

A feasibility study is performed for the development of a solid oral dosage form of an active ingredient.

Development Stages

The active pharmaceutical ingredient (API) undergoes characterization and salt selection. This process includes:

> Selection of the crystal state

> Particle size

> Solvates

> Hygroscopicity

> Stability

> Solubility

> Distribution

> Compressibility

> Flowability

> Forced degradation

> Stress tests

> Tests specific to the API

Compatibility studies of the API are thoroughly investigated, including:

> Drug-drug compatibility

> Drug-excipient compatibility

Characterization of the API involves the use of analytical techniques, including:

> SEM – Scanning Electron Microscopy

> XRPD – X-Ray Powder Diffraction Data Analysis

> DSC – Differential Scanning Calorimetry

> TGA – Thermal Gravimetric Analysis

> NMR – Nuclear Magnetic Resonance Spectroscopy

> HPLC – High-Performance Liquid Chromatography

> LC-MS – Liquid Chromatography–Mass Spectrometry

Formulation

Formulation development of solid oral dosage forms – tablets, capsules, and granules requires the utilization of numerous formulation strategies and processes. The major types of drug products, created by finished formulations are:

> Phase appropriate drug products for early stage clinical studies (API-in-a-bottle, API-in-a-capsule, fit-for-purpose formulations)

> Immediate release

> Delayed and Sustained Released

> Gastric protection

> Sublingual

> Effervescent

> Combination of 2 to 3 APIs

> Reformulation of drug products for new therapeutic applications, new dosage forms or different drug loading

> Anti-drug of abuse of controlled substances

To develop these drug products, state-of-the-art equipment have to be made use for efficient and scalable formulation and manufacturing processes:

> Direct Compression

> Encapsulation (Powder, Tablets, Granules, Hot Melt, Suspension)

> Wet Granulation (Low Shear, High shear & Fluidized Bed)

> Dry Granulation (Roller Compaction)

> Melt Granulation

> Spray Dry (Aqueous and Solvents)

> Drying (Fluidized Bed and Tray)

> Extrusion/ Spheronization

> Hot Melt Extrusion

> Coating (Pan and Fluidized Bed)

The evaluation of the prototype formulations (in-vitro / in-vivo) is a critical part of the formulation development process, as every drug product developed must meet the clients’ requirements. Manufacturing processes have to be robust, simple, cost-effective, and respectful of regulatory requirements.

The determination of the critical manufacturing steps & parameters, establishment & justification of the finished product specifications and a process implementation justification of the tests & specifications to be respected during production are the key components of a successful formulation.