Preformulation Studies for Tablet Formulation Development

Orally administered tablets are expected to be robust enough to withstand the rigors of manufacturing, packaging, and shipping, but readily disintegrate in the GI tract, and present the drug substance for rapid and complete dissolution and absorption from the GI tract. Additionally, the tablets should have an acceptable shelf-life. The tablet manufacturability and performance are dependent, among other things, on the physicochemical properties of the drug substance. A comprehensive characterization of the drug substance is necessary rational formulation development. The characterization of the physicochemical and mechanical properties of the active pharmaceutical ingredient (API) is referred to as pre- formulation. Preformulation also includes the evaluation of the compatibility of the API with potential excipients. During the drug development process, a general evaluation of physicochemical properties of a chemical compound is performed, with a goal of ascer- taining its druggability. Additional studies, related to tablet dosage form development, are focused on specific properties relevant to this dosage form. The desired properties, from a commercial manufacture and product usage, include: (i) ease of manufacture, (ii) hardness with very low friability, (iii) long shelf-life, (iv) rapid disintegration, and (v) rapid dissolution. The physicochemical properties of the drug substance will be the predominant determinant of the shelf-life as well as the dissolution behavior of the dosage form. In dosage forms where the API is not the major formulation component, the ease of man- ufacture, hardness, and friability can usually be controlled through excipients.