Abstract
The effects of grinding and drying (removal of water of crystallization) processes on the solidstate stability of ampicillin trihydrate were studied. The ground samples became more unstable as the grinding time increased. This phenomenon is considered to be due to a greater freedom of movement of water molecules, which are sufficiently free to participate in a solid-state hydrolytic reaction in the impaired lattice induced by grinding. A stabilization effect was observed when the ground sample was stored at high humidity, although ampicillin was susceptible to hydrolysis. This effect was interpreted in terms of a decrease of the ability of water molecules to move within the crystal. The dehydration of ampicillin trihydrate resulted in a higher disorder of the crystal structure. Partially dehydrated samples were unstable. However, and almost completely dehydrated sample was relatively stable because of the virtual absence of water able to participate in the hydrolytic reaction