Evaluation of Clay-Functionalized Wafers and Films for Nicotine Replacement Therapy via Buccal Mucosa

Abstract

The functional physicochemical properties of nicotine (NIC)-loaded composite freeze-dried wafers and solvent-evaporated films comprising hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA), stabilized with magnesium aluminium silicate (MAS), have been reported. The formulations were characterized for swelling capacity, mucoadhesion, in vitro drug dissolution properties in simulated saliva (SS) and PBS at pH 6.8, and ex vivo and in vitro permeation using pig buccal mucosa membrane and EpiOralTM buccal tissue culture, respectively; finally, the cell viability of the EpiOralTM tissues after contact with the NIC-loaded formulations was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the functional characteristics compared with those of commercially available NIC strips. Swelling and NIC release from the HPMC–SA wafers were more prolonged (30 min) compared to the commercially available NIC strips which disintegrated rapidly and released the drug within 5 min. Generally, swelling, mucoadhesion, and drug release was faster in PBS than in SS, and the presence of MAS was essential for maintaining a high dose recovery compared to non-MAS formulations and commercial NIC strips, which showed lower percentage of NIC content, possibly due to evaporation during analysis. Permeation studies showed that the NIC released was able to cross both porcine buccal membrane and the EpiOralTM buccal tissue, with the latter showing higher permeation flux for all the formulations tested. All the NIC-loaded, MAS-stabilized formulations showed high tissue viability, with values above 80%, showing their great potential for use as buccal delivery platforms for NIC replacement therapy to aid smoking cessation.

Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation

“…Swelling due to water uptake allows initially stretched, twisted or entangled bioadhesive polymers to relax, resulting in rapid disentanglement of individual polymer chains and generating a macromolecular network of a specific size that increases the porosity of the film and initiates drug release [ 41 ]. However, too-extensive swelling may lead to discomfort for patients.…”

“…Indeed, a relationship exists between the swelling index and mucoadhesive strength, wherein the mucoadhesion increases with the degree of hydration until the point where hydration leads to an abrupt drop in adhesive strength due to disentanglement at the polymer–tissue interface [ 28 , 43 ]. Polymer swelling ensures that the polymer chains uncoil and promote hydrogen bonding and/or electrostatic interaction between polymer and mucin [ 41 , 44 ]. Moreover, the prompt hydration detected might be due to the hydrophilic properties of the HPMC and Proloc 15.…”

Oral Thin Films As a Remedy for Noncompliance in Pediatric and Geriatric Patients

“…Though fast dissolving oral thin films are typically placed on the tongue for rapid dissolution and swallowing, multipurpose oral thin films are increasingly being employed for initial buccal absorption and subsequent dissolution and eventual swallowing of the remaining free flowing gels, containing unabsorbed drug. A typical example is NiQuitin oral thin films for nicotine replacement therapy to aid smoking cessation [74]. This therefore requires use of permeation enhancers to improve the initial absorption of drugs into the systemic circulation [58].…”

Preactivated-thiolated polyacrylic acid/1-vinyl pyrrolidone nanoparticles as nicotine carriers for smoking cessation

“…The development of new nicotine formulations, such as mouth spray, drops/straw, lms, freeze-dried wafers, and more advanced creations, has been investigated. [11][12][13][14] Mucoadhesive drug delivery refers to a system that can adhere to the mucosal lining and provide prolonged residence time, localized delivery, fast action, and increased bioavailability. 15,16 Mucoadhesive drug delivery systems can be employed in the delivery of nicotine for smoking cessation as the formulation can adhere to the oral mucosa, and release nicotine in a controllable approach, thus reducing the smokers' dependency on smoking.…”