Solid-State Characterization And Engineering Of Two Antihistamine Drugs - Loratadine And Desloratadine

Abstract

With the implementation of Quality by Design (QbD), pharmaceutical product development is gradually transforming from an art based on empirical practice to a science based on knowledge of material and process. In this thesis work, we employed two classic antihistamine drugs – loratadine (Lor) and desloratadine (Des) as model compounds. The more superior tabletability of Lor than that of Des is explained by the bonding area (BA) and bonding strength (BS) model. The molecular origins of both BA and BS are systematically investigated, which can be applied to effectively improve mechanical properties and tableting performance of drugs. The problems of poor water solubility and dissolution rate of Lor at physiological pHs is overcome through crystal engineering that leads to a new multicomponent crystalline form of Lor with an artificial sweetener, saccharin. The sweet taste, enhanced solubility and dissolution rate, as well as acceptable physical stability of the new salt facilitate the development of a chewable tablet formulation, demonstrating the usefulness of crystal engineering in pharmaceutical development of chewable tablets. New insights into the relationship between crystal structure and macroscopic bulk powder compaction behavior were gained from this research.