Preparation and phase II clinical examination of topical dosage form for treatment of carcinoma colli containing bleomycin with hydroxypropyl cellulose.

Abstract

A new topical disk-like dosage form for carcinoma colli was prepared by direct compression of the mixture of bleomycin hydrochloride (BLM) and combination of hydroxypropyl cellulose (HPC) and other water soluble polymers. After in vitro examinations regarding water adsorption, release and dissolution of drug and other properties, the preparations were examined clinically in volunteer patients. A combination of HPC and Carbopol 934 (CP) [pharmaceutical resin adjuncts] seemed preferable as the vehicles, and the amount of BLM released from the preparation increased remarkably with an increase in concentration of HPC. The water absorbing property increased with an increase of CP. The preparation containing 30 mg of BLM, for which the preparative formula was designed according to the in vitro experiment, was administered to stage O to Ib carcinoma colli patients. There was a continuous release of BLM for longer than 24 h. In 3 of 9 patients, no cancerous foci were found after local therapy using 90-195 mg of BLM; remnant foci found in the other 6 patients were very few. The normal mucosa was not affected by BLM. More cures might be expected if the therapy could be continued for longer periods.