This work investigated the influence of liquid vehicles on the release, mucosal permeation and deposition of cannabidiol (CBD) from liquisolid systems. Various vehicles, including EtOH, nonvolatile low- and semi-polar solvents, and liquid surfactants, were investigated. The CBD solution was converted into free-flowing powder using carrier (microcrystalline cellulose) and coating materials (colloidal silica). A physical mixture of the CBD and carrier–coating materials was prepared as a control. The non-crystalline state of CBD in the liquisolid systems was confirmed using XRD, FTIR and SEM studies. The CBD liquisolid powder prepared with volatile and nonvolatile solvents had a better CBD release performance than the CBD formed as the surfactant-based and control powders. The liquisolid systems provided the CBD permeation flux through porcine esophageal mucosa ranging from 0.68 ± 0.11 to 13.68 ± 0.74 µg·cm⁻²·h⁻¹, with the CBD deposition levels of 0.74 ± 0.04 to 2.62 ± 0.30 μg/mg for the dry mucosa. Diethylene glycol monoethyl ether showed significant CBD permeation enhancement (2.1 folds) without an increase in mucosal deposition, while the surfactants retarded the permeation (6.7–9.0 folds) and deposition (1.5–3.2 folds) significantly. In conclusion, besides the drug release, liquid vehicles significantly influence mucosal permeation and deposition, either enhanced or suppressed, in liquisolid systems. Special attention must be paid to the selection and screening of suitable liquid vehicles for liquisolid systems designed for transmucosal applications.

This study demonstrated the implementation of a liquisolid technique to formulate directly compressible orally disintegrating tablets (ODTs). Cannabidiol (CBD), a hydrophobic cannabinoid, was prepared as a liquisolid powder using microcrystalline cellulose–colloidal silicon dioxide as a carrier–coating material. Different liquid vehicles differing in their volatility, hydrophilicity, and viscosity were investigated. Each of the CBD–ODTs comprised CBD liquisolid powder (10 mg CBD), superdisintegrant, flavors, lubricant, and filler. The physical mixture (PM) ODT was prepared as a control. Ethanol-based ODTs (CBD–EtOH–ODTs) had comparable tablet properties and stability to CBD–PM–ODTs. ODTs with nonvolatile-vehicle-based liquisolid powder had lower friability but longer disintegration times as compared with CBD–PM–ODTs and CBD–EtOH–ODTs. Compression pressure influenced the thickness, hardness, friability, and disintegration of the ODTs. With a suitable compression pressure to yield 31-N-hardness-ODTs and superdisintegrant (4–8%), CBD–ODTs passed the friability test and promptly disintegrated (≤25 s). Times to dissolve 50% of CBD–PM–ODTs, CBD–EtOH–ODTs, and nonvolatile-vehicle-based CBD–ODTs were 10.1 ± 0.7, 3.8 ± 0.2, and 4.2 ± 0.4–5.0 ± 0.1 min, respectively. CBD–EtOH–ODTs exhibited the highest dissolution efficiency of 93.5 ± 2.6%. Long-term and accelerated storage indicated excellent stability in terms of tablet properties and dissolution. Nonvolatile-vehicle-based CBD–ODTs exhibited a higher percentage of remaining CBD. This study provides useful basic information for the development of ODT formulations using a liquisolid technique application.

Diarylheptanoids (DAs) characterized by a 1,7-diphenylheptane structural skeleton are considered a novel class of phytoestrogens. The DAs available in Curcuma comosa Roxb. (C. comosa) extract demonstrated significant estrogenic activities both in vitro and in vivo. This study aimed to develop and comprehensively evaluate a mucoadhesive vaginal gel for the sustained release of DAs. Different mucoadhesive polymers as gelling agents were investigated. C. comosa ethanolic crude extract was used as a source of DAs. All C. comosa gels were light brown homogeneous with pH within 4.4–4.6. Their flow behaviors were pseudoplastic with a flow behavior index of 0.18–0.38. The viscosity at a low shear rate varied from 6.2 to 335.4 Pa·s. Their mechanical and extrudability properties were associated well with rheological properties. Polycarbophil (PCP):hydroxypropyl methylcellulose (HPMC) blends had a higher mucoadhesiveness to porcine vaginal mucosa than those of PCP-based or HPMC-based gels. All C. comosa gels exhibited a sustained, zero-order DA release pattern over 72 h. Korsmeyer and Peppas equation fitting indicated a non-Fickian, case II transport release mechanism. C. comosa gels had good physical and chemical stability under low-temperature storage for up to 12 months. PCP:HPMC-based mucoadhesive gels could be a proper delivery system for vaginal administration of DAs.

In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using static diffusion cells coupled with fresh porcine esophageal mucosa. The CBD–vehicle solutions were applied at a fixed dose (~5 mg/cm²), and the corresponding permeation parameters were calculated. In neat vehicles, the permeation flux (J_ss) ranged from 0.89 ± 0.15 to 179.81 ± 23.46 µg·cm⁻²·h⁻¹, while the CBD deposition ranged from 11.5 ± 1.8 to 538.3 ± 105.3 μg·cm⁻². Propylene glycol (PG) and diethylene glycol monoethyl ether (DEGEE) yielded the highest permeability (P_s) and CBD deposition, while medium-chain triglycerides (MCT) yielded the lowest P_s and deposition. This was due to the difference in apparent partition coefficient (K), which is related to the solubility of CBD in the vehicle. The PG:DEGEE binary vehicle boosted J_ss (1.5–1.6 fold) and deposition (2.0–2.7 folds) significantly, compared to neat DEGEE. The combination of DEGEE with MCT dramatically enhanced J_ss (11–44 fold) and deposition (1.6–4.7 fold). The addition of lipophilic enhancers, laurocapram, and oleic acid, to PG:DEGEE and DEGEE:MCT vehicles significantly reduced J_ss (0.3–0.7 fold) and deposition (0.4–0.8 fold) while nerolidol had no effect. These permeation reductions were found to be related to modification of the K and/or diffusivity values. This study provides useful basic information for the development of CBD formulations intended for transmucosal delivery.