Temperature Stability and Bioadhesive Properties of Δ⁹-Tetrahydrocannabinol Incorporated Hydroxypropylcellulose Polymer Matrix Systems

Abstract

The purpose of this study was to determine and compare the bioadhesive profiles of hydroxypropylcellulose (HPC) polymer matrices as a function of delta9-tetrahydrocannabinol (THC) content. In addition, the effect of processing temperature on the stability of THC and its extent of degradation to cannabinol (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent. Bioadhesive measurements including peak adhesive force, area under the curve, and elongation at adhesive failure were recorded utilizing the TA.XT2i Texture Analyzer. Data obtained from these tests at various contact time intervals suggested that the incorporation of THC led to an increase in the bioadhesive strength of the HPC polymer matrices. To determine the stability of THC and the resulting CBN content in the matrices, three different processing temperatures were utilized (120, 160, and 200 degrees C). Post-production High Performance Liquid Chromotography (HPLC) analysis revealed that the processed systems contained at least 94% of THC and the relative percent formation of CBN was 0.5% at 120 degrees C and 0.4% at 160 degrees C compared to 1.6% at 200 degrees C. These findings indicate that the cannabinoid may be a plausible candidate for incorporation into systems utilizing hot-melt extrusion techniques for the development of an effective mucoadhesive transmucosal matrix system for delivery of THC.

Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins

“…Therefore, in contrast to currently available drugs, topical administration of Δ 9 -THC would not only reduce the IOP but would also protect the retinal ganglionic cells against glutamate and N-methyl-D-aspartate-induced neurotoxicity. However, Δ 9 -THC is psychotropic, poorly soluble in aqueous media, and has undesirable side effects (10,11). Moreover, susceptibility to oxidation, hydrolysis, thermal, and photolytic degradation in the solution form make the design of Δ 9 -THC ophthalmic formulations a challenging task (11)(12)(13)(14).…”

A new strategy to enhance artificial ligament graft osseointegration in the bone tunnel using hydroxypropylcellulose

“…HPC is extensively used in oral formulations due to its non-toxic and non-irritant properties. In addition, it possesses mucoadhesive and hydrophilic characteristics [15,16,26]. In our study, we investigated the ability of an HPC coating to promote healing of PET artificial grafts in the tibial bone tunnel using a rabbit extraarticular tendon-bone healing model.…”

“…Because HPC has hydrophilic and bioadhesive properties [14][15][16], it is primarily used in oral and topical pharmaceutical formulations. However, it is not clear whether HPC-coated PET artificial ligament grafts have a greater osseointegration capability in the bone tunnel.…”

Pharmaceutical Applications of Hot-Melt Extrusion: Part II

“…In view of these limitations, several other routes of administration have been investigated to improve bioavailability of THC, namely pulmonary, ophthalmic, sublingual, rectal, and transdermal routes. The authors prepared THC transmucosal matrix systems by hot-melt extrusion, utilizing various processing aids (Munjal et al, 2006a(Munjal et al, , 2006bRepka et al, 2006). The chemical stability of the drug in the polymeric matrices was investigated with respect to processing temperature, processing time, formulation additives, and storage conditions.…”