Developing early formulations: practice and perspective.

Early formulations are prepared mostly for drug compounds at both discovery and preclinical stages and are used to animals via various routes such as oral and intravenous dosing. They serve the purpose of evaluating these compounds on a broad range of pharmaceutical interests, notably pharmacology (activity/efficacy), pharmacokinetics (PK), and toxicology. It is estimated that approx. 40% of all drug compounds discovered have certain delivery limitations due to poor solubility or poor bioavailability. This brings tremendous challenges to the scientists working in the field of early formulations. This study intends to cover a broad spectrum of early formulations including basic aspect and development aspect. On basic aspect, it summarized early formulation study purpose, objectives, dosing route, animal species, etc. It then evaluated a variety of dosage forms and solubility enhancement approaches including various solutions, suspensions, lipid-based formulations, solid dispersions, etc. On development aspect, this study broadly reviewed literatures and current practice in the field, the issues and challenges. It offered authors' own approaches and strategies including general development schemes for oral and for i.v., recommended excipient use range for oral and for i.v., experimental procedures for vitro serial dilution method, for kinetic solubility, etc. The study also discussed a number of case analyses and emphasized scientific rationales and experimental approaches in each of them. The study concluded with authors' summary and some comments on early formulation practice, thoughts and perspectives on its future trend. The study is a mixture of literature review and investigational research. It provides many useful information, practical procedures, and recommendations. It is expected that the study will fill the void of literature of such kind, and provide direct benefit to everyday practitioners in the field.