Evolution of Drug Delivery Systems for Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (RAS) is a disease marked by painful oral lesions on the buccal and labial mucosa or tongue. Drug delivery systems (DDS) for RAS include topical forms that manage wound healing, cover the ulcer, and relieve the associated pain. DDS targeting the oral mucosa face a major challenge, especially the short residence times in the mouth due to the effect of "saliva wash-out", which continually removes the drug. The objective of this review is to study the development of preparation forms and delivery systems of various types and preparations that have been used for RAS management from 1965 until February 2020. There are 20 types of DDS for RAS which were discussed in 62 articles. The preparations were classified into 4 preparation forms: liquid, semi-solid, solid, and miscellaneous. In addition, the ultimate DDS for RAS preparations is the semi-solid forms (41.94%), which include 5 types of DDS are gel, paste, patch, cream, and ointment. This preparation was developed into new preparation form (11.29%), such as adhesive alginates, dentifrice, OraDisc, membranes, bioresorbable plates, pellicles, and gelosomes. Generally, the mucosal drug delivery system is the method of choice in RAS treatment because the ulcer is commonly located in the oral mucosa. In conclusion, these preparations are designed to improve drug delivery and drug activity for the treatment of RAS ulcers. Moreover, almost all of these DDS are topical preparations that use various types of mucoadhesive polymers to increase both residence time in the oral mucosa and pain relief in RAS treatment.