Approach to the Determination of Hydrate Form Conversions of Drug Compounds and Solid Dosage Forms by Near‐Infrared Spectroscopy

Near-infrared (IR) spectroscopy is used for the rapid, nondestructive identification and quantitation of the hydrate form of drug compounds forming both single and multiple hydration states. Near-IR is shown to be useful in both bulk drug and in finished solid dosage forms. The capability of near-IR to nondestructively analyze samples allows the kinetics of hydrate form conversions to be measured directly in formulated products. In addition, the environmental conditions for stability of the individual hydration states are mapped out using near-IR spectroscopy. Detailed molecular mechanisms are given to account for the near-IR spectral changes that occur upon hydration. The technique is applied in both laboratory studies as well as in a process environment for at-line analysis of active pharmaceutical ingredient hydration state during pharmaceutical processing.