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

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.

Nicotine stabilization in composite sodium alginate based wafers and films for nicotine replacement therapy.

Composite wafers and films comprising HPMC and sodium alginate (SA) were formulated for nicotine (NIC) replacement therapy via the buccal route. Magnesium aluminium silicate (MAS) was added in different concentration ratios (0.25, 0.5, 0.75) to stabilize NIC and its effect on mechanical properties, internal and surface morphology, physical form, thermal properties, swelling, mucoadhesion, drug content and release behaviour of the formulations was investigated. MAS changed the physico-mechanical properties of the composite formulations causing a decrease in mechanical hardness, collapsed wafer pores, increased roughness of film surface, increase in crystallinity and decreased mucoadhesion of the wafers. However, MAS increased swelling in both films and wafers as well as interaction between NIC and SA, which increased drug-loading capacity. Further, MAS resulted in rapid and slow release of NIC from wafers and films respectively. The results suggest that the ideal formulation for the stabilization of NIC in the composite formulations was MAS 0.25.

Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine.

Polysaccharide Based Formulations for Mucosal Drug Delivery: A Review.

There has been increased interest in novel drug delivery systems to be administered via mucosal routes as an alternative to the currently used traditional routes such as parenteral (injections) and oral routes of administration. This is due to the several advantages they offer including avoiding first pass metabolism in the liver for oral administration and local activity which avoids the need for high systemic doses. To achieve the foregoing objectives, bioadhesive vehicles are required that ensure prolonged residence time to achieve systemic bioavailability via substantial drug absorption or significant drug concentration for local action. The drug delivery system is also required to be non-deleterious to the site of application and be well tolerated by vulnerable groups such as paediatric and geriatric patients. These essential characteristics are mainly satisfied by naturally occurring polymers, including polysaccharide based polymers which have the advantage of biocompatibility, biodegradability and therefore safety. This review discusses various bioadhesive polymers of polysaccharide origin formulated into a variety of dosage forms for drug delivery via the body's mucosal (moist) surfaces including ocular, oral (buccal and sublingual), nasal, gastrointestinal and vaginal mucosa, as well as moist wound sites. The anatomy and / or physiology of each site, coupled with the unique challenges each poses, the strategies employed for ensuring therapeutic efficacy, as well as the current state of the art will also be covered.

Composite alginate and gelatin based bio-polymeric wafers containing silver sulfadiazine for wound healing.

Lyophilized wafers comprising sodium alginate (SA) and gelatin (GE) (0/100, 75/25, 50/50, 25/75, 0/100 SA/GE, respectively) with silver sulfadiazine (SSD, 0.1% w/w) have been developed for potential application on infected chronic wounds. Polymer-drug interactions and physical form were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively, while morphological structure was examined using scanning electron microscopy (SEM). Functional characteristics [(mechanical hardness and adhesion using texture analyzer, and swelling capacity)] of blank wafers were determined in order to select the optimal formulations for drug loading. Finally, the in vitro drug dissolution properties of two selected drug loaded wafers were investigated. There was an increase in hardness and a decrease in mucoadhesion with increasing GE content. FTIR showed hydrogen bonding and electrostatic interaction between carboxyl of SA and amide of GE but no interaction between the polymers and drug was observed, with XRD showing that SSD remained crystalline during gel formulation and freeze-drying. The results suggest that 75/25 SA/GE formulations are the ideal formulations due to their uniformity and optimal mucoadhesivity and hydration. The drug loaded wafers showed controlled release of SSD over a 7h period which is expected to reduce bacterial load within infected wounds.