Zeolites in biomedical application:: Zn-exchanged clinoptilolite-rich rock as active carrier for antibiotics in anti-acne topical therapy

A clinoptilolite-rich rock was evaluated as inorganic Zn2+ releasing carrier for antibiotic erythromycin. The perspective is its use in the topical treatment of acne, a diffused skin pathology, given the efficacy of zinc-erythromycin combination against resistant Propionibacterium strains. The tested rock is an ash-rich epiclastite collected in Northern-Central part of Sardinia island (Italy). ICP chemical analyses of the bulk rock evidenced a composition compatible with topical applications. A 66 wt.% of clinoptilolite content was determined by means of XRD analysis (reference intensity ratio [RIR] technique). EDS chemical analyses of zeolite crystals were performed on polished thin section. The CEC of the rock is 1.45+/-0.08 meq/g. Using a specific exchange method, the material was previously Na-conditioned then Zn-conditioned. A substantially complete Zn-form was obtained, as demonstrated by AAS analyses. A back-exchange reaction toward Na-form was performed in the same conditions (65degreesC in 1 M NaCl solution): zinc release was fast and almost complete (94%). Zn-conditioned powder was then micronized to achieve a volume/surface ratio suitable for a topical therapy. After micronization, the specific surface area, determined by BET gas adsorption, was 30.2 m(2)/g, and 92% of the powdered rock was lower than 30 mum in size (measured by a Coulter Counter apparatus); the so-called "volume-surface diameter" was 6.48 mum, compatible with the intended topical application. Zn2+ release was measured on micronized rock at 37 degreesC both in physiologic solution as in 0.05 M KH2PO4/Na2HPO4 buffer. Also in these conditions, a prompt and significant zinc release was recorded: after 30 min, 68% and 60%, respectively. Erythromycin was charged onto the micronized material using a solvent evaporation method. HPLC determinations showed that 85% of the drug contacted with the carrier was loaded. The simultaneous release of zinc and erythromycin were evaluated in phosphate buffer. Eighty-two percent of the loaded antibiotic was released after 30 min. Zinc exchange is substantially unaffected by the contemporary drug release. The request to file an international patent for this pharmaceutical application has been accepted by the European International Preliminary Examination Office. (C) 2004 Elsevier B.V. All rights reserved.