Solid forms of pharmaceutical molecules

A drug discovery is characterized by two stages. The first in terms of time is called „lead structure“, followed by a so called „drug candidate“ stage. The lead structure stage involves selecting the optimum molecule of the pharmaceutical, while drug candidate stage means selecting the optimum solid form. Usually, 5 – 10 candidates pass to the drug candidate stage and the result is the selection of the final solid API (Active Pharmaceutical Ingredience) for the ensuing formulation of the solid dosage form. The lead structure stage concerns only the discovery of the original drug, the drug candidate stage may concern also generics (a drug which is bioequivalent with original and is produced and distributed after the patent protection of the original). The choice of the optimal API for a specific solid drug formulation means the optimization of its properties. The most important properties of API include its solubility, dissolution rate and permeability, which are closely related to the oral bioavailability of the drug. Apart from these, there are other properties influencing functional and technological parameters of the API and its patent non-collision status (Table I). For the selection of the optimal API, several dozens of solid forms may be available from one molecule. An example is atorvastatin calcium, a drug used for the treatment of high cholesterol, for which more than 60 solid forms are patented [1]. Piroxicam, a non-steroidal anti-inflammatory drug, was synthesized in more than 50 forms [2] and more than 100 forms are described for sulphathiazol [3], a local antimicrobial agent. A review of possible chemical and physical types of pharmaceutical solid forms is given in Table II. In the case of multicomponent compounds the reduction in number of solid forms is given by the condition of pharmaceutical acceptability of the fellow component (e.g. counterion in the case of salts), see GRAS (Generally Recognized as Safe [4]).