Formulation development and in vivo evaluation of a novel bioadhesive lozenge containing a synergistic combination of antifungal agents

• Published in: International journal of pharmaceutics 1998-10, Vol.173 (1), p.13-24
• Main Authors: Codd, Janet E, Deasy, P.B
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Bioadhesive lozenges; Biological and medical sciences; Chlorhexidine acetate; General pharmacology; Medical sciences; Miconazole nitrate; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Salivary levels; Synergy
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00228-2

Two novel bioadhesive antifungal lozenges were developed. Both were two-layered with an upper modified-release drug-containing layer and a lower bioadhesive layer composed of drum-dried waxy maize starch and Carbopol 980 to facilitate application to the oral mucosa. The first type of lozenge contained miconazole nitrate as a spray-dried form containing acacia and Cremophor RH40 to increase the dissolution of the poorly soluble azole, plus flavourings. The second type also contained chlorhexidine acetate in the drug layer, as both drugs had been reported to act synergistically. In vivo release of drug(s) into saliva was assessed in a group of healthy volunteers, with the lozenges located in an upper posterior site in the oral cavity. Therapeutic levels were achieved for extended periods of time with both formulations. Intra-subject variation was greater than inter-subject variation. By examining salivary drug concentrations obtained when the second formulation was applied to an upper anterior location, the release of drugs was shown not to be significantly affected by the location within the oral cavity. In comparison to a proprietary oral gel formulation, the new bioadhesive lozenges produced much more uniform and effective salivary levels of miconazole nitrate over a prolonged period.