Early Phase Formulation Development Services

Pharmaceutical development evaluation already at the early drug development stage is essential for selecting the right NCE and formulation to reduce the attrition rate in the late-stage development. These activities streamline efficacy/toxicology evaluations, allowing pharmacologically effective and developable molecules to reach the clinic and eventually patients.

The integration and close collaboration of preclinical and clinical development teams accelerate the FIH product development process by utilizing already available pre-formulation and bioavailability information and experience gained during preclinical formulation development. It also helps identify obstacles and apply the right formulation strategies early in the drug development process to avoid costly late-stage failures, significantly saving time and costs.

Pre-formulation identifies characteristics of NCEs, which are decisive parameters for the in vitro or in vivo performance of a drug. Pre-formulation assists scientists in screening/prioritizing lead candidates based on their physicochemical and biopharmaceutical properties.

Pre-formulation is the foundation of formulation development. Physicochemical, biopharmaceutical, physico-technical, solid-state, and stability parameters are essential to guide the selection of formulation technologies.

The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the biological system site.

The movement of the drug in the biological system is influenced by many factors such as routes of administration, physicochemical drug properties, physiological factors (e.g. gastrointestinal pH, gastric emptying, small intestinal transit time, bile salt, absorption mechanism, food, metabolism), manufacturing technique, dosage form, and excipients. Understanding the interrelationship of these factors leads to biopharmaceutical and science-based drug product developments.

Incomplete oral absorption could be due to poor solubility, poor intestinal permeability, or presystemic metabolism. Incomplete oral bioavailability can often be surmounted through formulation efforts.

We can enhance the oral bioavailability through formulation efforts using solubilizers, pH adjustment, cosolvents, complexing agents, permeation enhancers, and enabling technologies (solid dispersion, particle size reduction and lipid-based drug delivery systems).

By identifying potential limiting steps for oral absorption of a compound (including dissolution, solubility, permeability, and limited metabolism process), understanding the physicochemical properties of a compound, recognizing physiological processes affecting drug absorption, along with awareness of a drug's BCS and DCS characteristics, pharmaceutical scientist can better predict formulation approaches that can maximize the drug’s bioavailability.

Formulations play a crucial role in assessing the biological properties of a molecule during drug discovery. Maximizing exposure is the primary objective of early animal experimentation to avoid discarding developable compounds with the desired pharmacologic properties.

Diversity in the physiology between various animal species, routes of administration, limited compound amount, and limitations posed by specific pharmacological models make formulation development much more challenging. Consistency in the exposure is also a key aspect as significant variations are observed in early NCE batches.

Additionally, preclinical tox (GLP) studies at early development, require NCE formulations that are simple, robust, provide ease of preparation, convenient to deliver to animals with minimal ancillary effects of vehicle and provide provision of high and dose-related systemic exposures in animals relative to anticipated human exposures to facilitate determination of tox profiles.

The selection and development of effective formulation and drug delivery strategies are essential to achieve this