Mucoadhesive buccal tablets for the delivery of nicotine and Delta9-tetrahydrocannabinol.

Nicotine replacement therapy (NRT) is restricted to monotherapy with either a type A product providing rapid nicotine delivery or a type B product providing controlled nicotine delivery. Biphasic buccal adhesive nicotine tablets have been prepared with the intention of providing a combination of type A and type B approaches to NRT in a single dosage form to improve on the shortcomings of existing NRT treatments. Controlled release layers were prepared using crystalline nicotine hydrogen tartrate salt in a dry blend with adhesive and controlled release excipients. Powder blends were compressed to form 6 mm tablets. Release profiles indicated that a combined matrix of Carbopol 934® (C934) and hydroxypropylcellulose (HPC) could sustain release of nicotine for 4 hours at a rate approaching zero order release. The release of nicotine for this matrix was controlled by an anomalous transport mechanism dependent on both drug diffusion and polymer relaxation. Investigation of these controlled release layers indicated that both hydrogen bonding and polymer entanglement with the mucus layer was responsible for adhesion of the formulations to animal buccal mucosa. Maximum adhesive force reached a peak at 20% w/w C934 possibly due to saturation of hydrogen bonding groups at the tablet / mucus interface. Work of adhesion increased linearly with C934 concentration due to increased physical penetration of the polymer chains into the mucus at higher concentrations. Alternatively, polysaccharide matrix formers including xanthan gum, karaya gum, guar gum and glycol chitosan were investigated for the ability to provide controlled nicotine release and adhesion to animal buccal mucosa. Different release mechanisms were identified in the polysaccharides including anomalous transport, (xanthan gum, guar gum, glycol chitosan), Case II transport indicating zero order release (xanthan gum and guar gum at 50% w/w) and Super-Case II transport indicating a disintegration type matrix (karaya gum). The rank order of adhesive strength of the tablets provided by the polysaccharide excipients was glycol chitosan > xanthan gum > karaya gum > guar gum. Adhesive forces recorded were lower than that recorded for C934. Bilayer tablets produced an initial burst release of nicotine followed by controlled release of nicotine for up to 4 hours. This biphasic type release was identified in both in vitro and in vivo conditions. In vivo work indicated that nicotine release from the fast release layer was similar to that produced by nicotine gum and nicotine release rates from the controlled release layer were similar to low strength nicotine patches. The tablets adhered to human buccal mucosa for 4 hours in in vivo studies. There is great potential for the use of cannabinoids, particularly Delta9 - tetrahydrocannabinol (Delta9-THC), in a number of legitimate medical conditions. Buccal tablets containing Delta9-THC were prepared in an attempt to provide a standardised dose of Delta9-THC at controlled rates via the buccal mucosa. Tablets were prepared by adding an ethanolic solution of Delta9-THC to a dry powder blend of the other excipients. The resulting dried powder was compressed to form 6 mm Delta9-THC buccal adhesive tablets. Release profiles indicated low rates of drug release in in vitro conditions (< 20%) from the combined C934 / HPC matrix used for nicotine. Release enhancers including the bile salt, sodium deoxycholate, and the surfactant, sodium lauryl sulphate, reduced Delta9-THC release further by interaction with other tablet excipients. These interactions were identified using differential scanning calorimetry. These studies have concluded that a bilayer tablet providing biphasic nicotine release shows excellent potential as a novel form of NRT, combining type A and type B approaches to NRT in a single formulation. Further investigation is required to assess the potential for controlled buccal delivery of Delta9-THC from the formulations prepared in this study.

Author dc:creator

• Park, Calum R.

Advisor dc:contributor.advisor

• D.L. Munday

• Nicotine replacement therapy (NRT)
• Buccal drug delivery
• Biphasic release formulation
• Mucoadhesive tablets
• Controlled drug release
• Delta9-tetrahydrocannabinol (THC)

Language dc:language

en

Identifier

oai:rgu-repository.worktribe.com:2807517
https://doi.org/10.48526/rgu-wt-2807517

OAI identifier oai:identifier

oai:rgu-repository.worktribe.com:2807517