COREALIS Pharma’s pre-formulation development service takes clients 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.
The active pharmaceutical ingredient (API) undergoes characterization and salt selection. This process includes:
- Selection of the crystal state,
- Particle size,
- Forced degradation,
- Stress tests,
- Tests specific to the API.
Compatibility studies of the API are thoroughly investigated. These include:
- Drug-drug compatibility,
- Drug-excipient compatibility.
Characterization of the API involves the use of analytical techniques including, but not limited to,
COREALIS Pharma offers complete services for the formulation development of solid oral dosage forms – tablets, capsules, and granules. COREALIS Pharma’s experts have developed and manufactured a large variety of drug products where numerous formulation strategies and processes have been utilized. Their expertise is made available to clients for the development of the following types of drug products:
- 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;
- Combination of 2 to 3 APIs (505(b)(2));
- Reformulation of drug products for new therapeutic applications, new dosage forms or different drug loading (505(b)(2));
- Anti-drug of abuse of controlled substances.
To develop these drug products, the experts have at their disposal state of the art equipment 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 (FB)),
- Dry granulation (Roller Compaction),
- Melt granulation,
- Spray dry (Aqueous and Solvents),
- Drying (FB and Tray),
- Extrusion/ Spheronization,
- Hot Melt Extrusion,
- Coating (Pan and FB).
COREALIS Pharma recognises that the evaluation of the prototype formulations (in vitro and/or in vivo) is a critical part of the formulation development process and their scientists invest a lot of effort and resources in order to ensure that each and every drug products developed meets the clients’ requirements. COREALIS Pharma thrives to develop manufacturing processes that are robust, simple, cost-effective, and respectful of regulatory requirements.
The COREALIS Pharma team provides thorough service which extends to 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. COREALIS Pharma’s formulation development may be valid for patent approval.
COREALIS Pharma provides analytical methods development, qualification and GMP analytical services to exclusively support its internal formulation development and clinical supplies manufacturing projects. COREALIS Pharma prides itself on producing rapid, accurate, and precise results on the chemical and physical properties of raw materials and finished products. The phase appropriate analytical methods qualification/ validation and GMP analysis for release testing and stability studies are performed in order to respect the guidelines of regulatory agencies in the country where the clinical studies are held.
Pre-formulation and formulation development
This analysis of active pharmaceutical ingredients (API),
analytical methods development, and analysis of excipients, drug products intermediates and finished products includes, but is not limited to:
- impurities (related substances),
- content and blend uniformity,
- dissolution (UV, HPLC),
- degradation products (including forced degradation),
- solubility studies,
- stability studies,
- compatibility studies (API-API, API-Excipients),
- cleaning verification.
The stability studies are executed according to ICH guidelines.
Some of the specific analytic services offered include:
- identification and quantification of impurities and degradation products,
- photo stability studies,
- microbiological testing,
- analysis of the polymorphic form(s) of the active ingredients,
- determination and particle size and distribution,
- permeability studies (PAMPA or Caco-2),
- solubility determination, and
- water content determination.
The measurements of the physical and chemical properties of an API allows formulators to:
- select suitable API and API moieties that are suitable for oral solid dosage formulation;
- define formulation development strategies;
- identify API variability between different batches.