In vitro characterisation of calcium phosphate biomaterials loaded with lidocaine hydrochloride and morphine hydrochloride.

Calcium phosphate substitutes drug delivery systems are well known substances used in minor bone void-filling to release their therapeutic agent in situ. Few studies associating anaesthetics and analgesics have been performed to date. The aim of this work was to study the association of the analgesic, morphine, and the local anaesthetic, lidocaine, with a calcium deficient apatite matrix. Three types of biomaterials i.e. powders, granules and blocks, were prepared by isostatic compression, wet granulation and a combination of the two, evaluated and compared. The chemical structure of the associated therapeutic agent was studied and the characteristics of the drug delivery systems were appraised in terms of drug release. The integrity of the lidocaine hydrochloride structure, as determined by RMN (1)H, was confirmed regardless of the formulation technique used (isostatic compression or wet granulation). However, analyses of morphine hydrochloride by RMN (1)H revealed slight structural modifications. The association and formulation techniques that were used made it possible to obtain an in vitro release time varying from 1 to 4 days for lidocaine hydrochloride and from 1 to 3 days for morphine hydrochloride.