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

Joshua Boateng,Obinna Okeke

doi:10.3390/pharmaceutics11030104

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.

Highlights

Life threatening diseases such as lung cancer, chronic obstructive pulmonary disease, and cardiovascular diseases are usually associated with cigarette smoking (U.S Department of Health and Human Services, 2014)
HPMC–sodium alginate (SA) based wafers and films were analysed for swelling and NIC release properties using simulated saliva (SS) as medium to demonstrate the effect of the constituents of SS such as electrolytes and mucin on formulation performance
The swelling profile of NiQuitin® strips demonstrated a rapid swelling within 6 min and a higher swelling compared to the HPMC–SA based wafers and films but eroded rapidly after reaching its optimum swelling capacity

Summary

Introduction

Life threatening diseases such as lung cancer, chronic obstructive pulmonary disease, and cardiovascular diseases (e.g., coronary heart disease and stroke) are usually associated with cigarette smoking (U.S Department of Health and Human Services, 2014). These risks are significantly decreased when smoking is curtailed, depending on factors such as age, sex, physiology, and smoking frequency. The life expectancy of a smoker after cessation at 35 years could increase by 20–24% in men and 17–22% in women. The life expectancy of a smoker after cessation at 65 years could increase by just 2–3% in men and 4–5% in women. An active smoker of tobacco draws in smoke known as mainstream smoke which comprises 8% tar and 92% gaseous components, while the side-stream released at the burning tail of a lit cigarette contains a higher proportion of poisonous components such as nitric oxide and carbon monoxide [2], leading to risks of severe heart disease in non-smokers [3]

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