Application of viscometry and solubility parameters in miconazole patches development

• Published in: International journal of pharmaceutics Vol. 190; no. 1; pp. 91 - 101
• Main Authors: Minghetti, P., Cilurzo, F., Casiraghi, A., Montanari, L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.11.1999; Elsevier
• Subjects: Adhesiveness; Adhesives; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; Biological and medical sciences; Capillary viscometry; Chemistry, Pharmaceutical; Copolymer compatibility; Drug Compounding - instrumentation; Drug Compounding - methods; Drug Delivery Systems; Drug Stability; Evaluation Studies as Topic; General pharmacology; Kinetics; Medical sciences; Methacrylates - chemistry; Miconazole - chemistry; Miconazole - pharmacokinetics; Models, Theoretical; Patches formulation; Patches preformulation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Placebos; Solubility; Solubility parameter; Viscosity; Solubility parameter; Copolymer compatibility; Patches formulation; Capillary viscometry; Patches preformulation; Viscosity; Imidazole derivatives; Stability; Pharmaceutical technology; Control release polymer; Solubility; Molecular interaction; Drug carrier; Capillary viscosimeter; Percutaneous route; Antifungal agent; Dosage form; Methacrylate copolymer; Compatibility; Miconazole; Mathematical model; Patch; Bioadhesive system; Release; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00282-3

Nine binary mixtures of seven different methacrylic copolymer systems (Plastoid ® E 35 L (PLE) and Plastoid ® L 50 (PLL); Eudragit ® (Eu) NE, RL, RS, L, S) were tested as components of monolayer patches containing miconazole. Only three mixtures (PLE:EuNE, PLE:EuRL and PLE:EuRS) were suitable for the preparation of placebo matrices. Miconazole patches with good technological characteristics were obtained by using mixtures of PLE:EuNE and PLE:EuRL. The in vitro miconazole release rate from the two patches and from the patch prepared using only PLE were significantly different. The amounts of drug released in 24 h were quite satisfactory. A mathematical model based on capillary viscometry data was used for the evaluation of interactions between copolymers. This was useful to predict and understand the mechanisms related to the instability of the prepared mixture. The solubility parameters of the drug and of the matrix were also calculated. Miconazole release was faster when the difference between the solubility parameters of the matrix and of the drug was higher. A relationship between miconazole release rate and the difference of drug and matrix solubility parameters was found. Therefore, the solubility parameter could be applied in formulation studies of patches.