Technological and biopharmaceutical optimization of nystatin release from a multiparticulate based bioadhesive drug delivery system

• Published in: European journal of pharmaceutical sciences 2013-05, Vol.49 (2), p.258-264
• Main Authors: Pál, Szilárd, Nagy, Sándor, Bozó, Tamás, Kocsis, Béla, Dévay, Attila
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Adhesiveness; Animals; Antifungal Agents - chemistry; Bioadhesivity; Cellulose - analogs & derivatives; Cellulose - chemistry; Dissolution; Drug Delivery Systems; Excipients - chemistry; Guinea Pigs; Ileum; Intestinal Mucosa - chemistry; Micropellet; Nystatin; Nystatin - chemistry; Solubility
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.03.006

Formulation considerations of a new drug delivery system include controlling the site of release of the active ingredient, maintaining drug level for a suitable time and decreasing dosage frequency. In research and development practice, these therapeutic benefits can be attained by selecting suitable active ingredients and optimizing procedure parameters, determining the composition of the medicine, and dissolution properties. The aim of our study was to design a pharmaceutical preparation with increased local therapeutic effect in the therapy of gastrointestinal candidiasis. The polyene antibiotic nystatin may be an optimal choice for active agent, incorporated in a bioadhesive multiparticulate system. Choosing the proper excipients in the proper dosage form and ensuring prolonged residence time may further improve the optimal treatment. Using an experimental design, the micropellets were prepared with 5% nystatin content, taking the factors average pellet size (∼200 to ∼800μm) and the amount of applied carbomer and hydroxyethylcellulose (0–5%) into consideration. Dissolution of the active ingredient was detected by UV spectrophotometric and microbiological assay. The bioadhesive character of the multiparticulate dosage form was examined by ex vivo wash-off test. The only factor which significantly influenced the examined parameters was average pellet size. The proportion of applied bioadhesive excipients had significance mostly in interactions with average pellet size. Eventually, optimized drug release (5–10min mean dissolution time, 50–55% bioadhesion retention) could be achieved with 550μm pellet size, containing carbomer and hydroxyethylcellulose in 85:15 ratio.