Beyond Nicotine: Buccal Films for Multi-Drug Delivery in Smoking Cessation

Smoking cessation remains a significant global health challenge, with current pharmacotherapies often yielding suboptimal long-term abstinence rates due to complex withdrawal symptoms and varied individual responses. This review explores the innovative potential of mucoadhesive buccal films for multi-drug delivery as a sophisticated approach to enhance smoking cessation outcomes. While nicotine replacement therapies (NRTs) address physical dependence, their limitations, coupled with the side effect profiles and inconsistent efficacy of non-nicotine pharmacotherapies like bupropion and varenicline, highlight an unmet need for more integrated and patient-centric solutions. Buccal films, by leveraging the oral mucosa's unique characteristics—high vascularization, bypass of first-pass metabolism, and direct systemic absorption—offer a versatile platform for delivering multiple active pharmaceutical ingredients (APIs). This article provides a comprehensive overview of the rationale for combination therapy, the challenges in coformulating disparate drugs into mucoadhesive buccal films, advancements in polymer science and formulation techniques, and the critical in vitro/ex vivo characterization methods. It critically discusses the synergistic potential of co-delivering nicotine with agents like bupropion or varenicline to address both physical cravings and neuropsychological aspects of addiction. Furthermore, the review identifies current hurdles in optimizing multi-drug buccal film formulations, ensuring their stability, and facilitating their clinical translation, outlining future research directions to realize their full therapeutic promise in combating tobacco dependence.