The Physicochemical Principles Governing Nicotine Delivery from Oral Nicotine Pouches

Nicotine pouches represent a rapidly expanding category of tobacco-free oral nicotine products. While these products are often compared primarily on the basis of nicotine content, evidence from in vitro dissolution/permeation studies and controlled clinical pharmacokinetic studies shows that nicotine delivery is governed by a complex interplay between physicochemical and formulation-related parameters. Moisture content, water activity, pH, nicotine speciation, matrix composition, particle morphology, and pouch architecture collectively influence nicotine dissolution, transport, and absorption through the oral mucosa. This review examines nicotine pouches from a pharmaceutical and drug-delivery perspective, treating them as engineered oral delivery systems rather than conventional consumer products. The mechanisms governing nicotine release are discussed in relation to acid-base chemistry, diffusion phenomena, hydration dynamics, and matrix design. Emphasis is also placed on the distinction between moist and dry pouch formulations and how these product families differ in hydration state, transport behavior, sensory properties, and release kinetics. The review further evaluates matrices, humectants, pH modifiers, nicotine sources, and emerging alternative carrier materials. Together, in vitro characterization and clinical PK data indicate that nicotine delivery depends on the coupled effects of water availability, matrix structure, nicotine release and local pH conditions. Understanding nicotine pouches as controlled oral delivery systems provides a framework for improved product characterization, more meaningful performance comparisons, and development of technologies with tailored pharmacokinetic profiles.