Development of Film Dosage Form Containing Allopurinol for Prevention and Treatment of Oral Mucositis

Film dosage forms (FDs) containing allopurinol (AP) were prepared using a casting method with water-soluble polysaccharides, such as sodium alginate (ALG), and the release profile of AP from FDs was investigated in limited dissolution medium. Some ALGs were able to form FDs incorporating AP, and the thickness was about 50？μm. All FDs were easy to handle, though the rheological properties varied with ALG species. AP was homogenously present throughout the FDs and was released with disintegration in 10？mL of physiological saline. These results confirmed that FDs are useful for preventing or treating localized problems in the oral cavity, such as mucositis. FDs are also useful for administering drugs to cancer patients receiving chemotherapy and/or radiotherapy. 1. Introduction The xanthine oxidase inhibitor allopurinol (AP) is a drug used for the treatment of gout. AP has also been used to prevent and treat oral mucositis (mouth ulcers) in cancer patients receiving chemotherapy and/or radiotherapy [1–3]. In the treatment of mucositis, direct application of AP to the oral mucosa is necessary to avoid the systemic action seen after gastrointestinal absorption as the antioxidant activity of AP will result in lowering the activity of anticancer drug such as methotrexate. For example, AP suspensions (1？mg/mL) are freshly prepared in the hospital, and the patient gargles with the preparation [4]. This method for preventing mucositis is simple and effective; however, these preparations are not stable for long-term preservation, and it is difficult to control the amount of AP during gargling, although the dose is not sufficiently high to induce systemic effects in the event of erroneous swallowing. Recently, oral disintegration (OD) dosage forms such as OD tablets have become widely utilized, as they are useful in patients who have difficulty swallowing regular tablets [5, 6]. Film dosage forms (FDs) are also anticipated to be useful in oral care [7–9]. The active compound present in FDs is spread in the oral cavity as the form disintegrates on contact with saliva, and the disintegration profile of FDs can be varied by modifying the film base [10]. However, the drug loading capacity of FDs is typically very low, and the drug incorporated into FDs should be selected carefully. FDs are generally prepared using a water-soluble polymer base for immediate dissolution in saliva. As various polysaccharides have been used as additives for drug preparation or food ingredients because of the safety on peroral administration, they are candidate materials for FD preparation.