Design and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod

• Published in: International journal of pharmaceutics 2006-01, Vol.307 (2), p.318-325
• Main Authors: Donnelly, Ryan F., McCarron, Paul A., Zawislak, Agnieszka A., David Woolfson, A.
• Format: Article
• Language: English
• Subjects: Adhesiveness; Administration, Topical; Aminoquinolines - chemistry; Aminoquinolines - metabolism; Animals; Animals, Newborn; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Bioadhesive; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Delayed-Action Preparations; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug delivery; Drug Design; General pharmacology; Imiquimod; In Vitro Techniques; Medical sciences; Neoplastic; Ointments; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin - chemistry; Skin - metabolism; Swine; Tensile Strength; Tissue Adhesives
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.10.023

Clinical use of the imidazoquinoline immunomodulator imiquimod for the topical treatment of dysplastic and neoplastic lesions has increased markedly in recent years. However, despite guidance from the manufacturer of the proprietary imiquimod cream, there seems to be little consensus between clinicians as to the topically applied dose. Given that patients often apply the cream themselves at home, further dosing variability is expected and, consequently, accurate comparison of the results of different published studies is difficult. This paper describes, for the first time, the formulation and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod as well as a new HPLC method for sensitive fluorescence determination of imiquimod released from such systems. Patches containing imiquimod loadings of 4.75, 9.50 and 12.50 mg cm −2 all released significantly more drug across a model membrane than the proprietary cream over a period of 6 h. Inclusion of imiquimod in patches did not adversely affect their physicochemical properties. Of major importance, patches contained defined drug loadings per unit area; therefore, their use could reduce inter-clinician variability. This would make critical comparison of clinical studies and determination of an appropriate imiquimod dose for successful treatment much simpler. Since bioadhesive formulations are capable of adhering to body tissues in moist environments, the use of a bioadhesive patch system may allow extension of the clinical uses of imiquimod to the treatment of neoplastic conditions of the oral cavity and cervix, as well as the vulva.