[Interaction between macromolecular adjuvants and drugs. 25. The effect of cellulose ether on the solubility characteristics of benzodiazepine derivatives].

The technological processing of the benzodiazepine derivatives chlordiazepoxide, medazepam, diazepam, nitrazepam and clonazepam with methyl cellulose (mc) and hydroxyethylcellulose--especially physical mixtures and evaporates--led to an improved dissolution of the problem drugs. The effect of the adjuvants is remarkable in the initial phase of the dissolution and very distinctive at the end of the experiment. Obviously there is no relation between saturation solubility and dissolution. Only with nitrazepam and clonazepam, but less clearly with medazepam, an increase of solubility by the mc-trituration was observed. Studies of the binding showed a concentration and temperature dependent interaction of the benzodiazepines diazepam, clonazepam, medazepam and nitrazepam, to mc. As X-ray diffraction and differential thermoanalysis gave no interpretation for the improved dissolution behaviour of drug/adjuvant preparations, it is assumed that a high distribution of the drug particles in the dissolution medium by the preceding treatment with cellulose ether is the main reason for the increase of the dissolution rate.