Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability <1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-hydroxy-Δ9-THC. Maximal plasma concentrations of both Δ9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11-hydroxy-Δ9-THC, which is mainly formed in the liver from Δ9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1–2 h and suggested progressive accumulation after the multiple dose treatment.

Sublingual Delivery of Astaxanthin through a Novel Ascorbyl Palmitate-Based Nanoemulsion: Preliminary Data

Astaxanthin is a carotenoid extracted from several seaweeds with ascertained therapeutic activity. With specific reference, astaxanthin is widely used in clinical practice to improve ocular tissue health and skin protection from UV ray damages. Despite its well-documented pleiotropic actions and demonstrated clinical efficacy, its bioavailability in humans is low and limited because of its hydrophobicity and poor dissolution in enteric fluids. Furthermore, astaxanthin is very unstable molecule and very sensitive to light exposure and thermal stress. Taken together, these pharmacological and chemical–physical features strongly limit pharmaceutical and nutraceutical development of astaxanthin-based products and as a consequence its full clinical usage. This work describes the preliminary in vitro investigation of sublingual absorption of astaxanthin through a novel ascorbyl palmitate (ASP) based nanoemulsion.

Sublingual route for systemic drug delivery

Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a rapid onset of action and better patient compliance than orally ingested tablets. Sublingual literally meaning is “under the tongue”, administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first‐pass metabolic processes giving acceptable bioavailability. Sublingual technology is convenient for dosing in geriatric, pediatric and psychiatric patients with dysphagia. Sublingual drug delivery shows fast therapeutic action than orally ingested drugs with fewer side effects. This review highlights advantages, disadvantages, different sublingual Gland, sublingual formulation such as tablets, films drops, sprays etc, evaluation parameters. Keywords: Sublingual delivery, dysphagia, sublingual gland, improved bioavailability, evaluations.