Development and Assessment of a Mucoadhesive Formulation Incorporating Phenytoin for Wound Healing

Abstract This study aimed to develop flexible wafers for drug delivery to enhance wound healing. Sodium phenytoin, a known therapeutic agent, and chitosan, a biodegradable polymer with wound healing properties, were key components of the formulations. The study investigated the impact of various factors, such as the addition of propylene glycol (PG) to improve flexibility, and the combination of alginate, chitosan, and hydroxypropyl methylcellulose (HPMC) to achieve extended drug release and mucoadhesion. Results showed that increasing the amount of PG in the formulation improved flexibility but reduced mucoadhesion. Alginate and chitosan, when combined, formed polymer filaments, while HPMC and PG demonstrated high mucoadhesion. Drug release tests indicated that formulations with higher HPMC content exhibited slower release rates. Additionally, phenytoin was successfully incorporated into the alginate/chitosan polymer matrix, as confirmed by differential scanning calorimetry (DSC) and electron microscopy. In vivo evaluation using animal models demonstrated the effectiveness of the wafer containing phenytoin sodium in promoting faster wound healing compared to the drug-free wafer and phenytoin ointment. Pathology results revealed increased epidermal cell proliferation, the formation of a comprehensive layer of epidermis, and the appearance of hair follicles and dermis layer in the wafer-treated wounds. Furthermore, the wafer formulation containing 0.01% phenytoin exhibited complete healing by the twelfth day of treatment. The study highlights the potential of sodium phenytoin and the developed wafer formulation in improving wound healing outcomes. The sustained drug release and adhesive mucosa properties of the wafer contribute to its enhanced efficacy. Further research is warranted to gain a comprehensive understanding of the diverse effects of sodium phenytoin on wound healing and optimize the formulation for clinical applications.