Search Results (7)

Background: Effective and timely treatment of vitamin B12 deficiency in childhood is crucial because it can lead to serious issues, including delayed growth and neuromotor development. Available treatment options include oral, intramuscular, and sublingual administration. Aim: This study investigated the efficacy of a new dosing protocol for sublingual methylcobalamin. Materials and Methods: In total, 312 patients with vitamin B12 deficiency (serum level < 250 ng/L) were divided into two groups based on their treatment type: intramuscular cyanocobalamin (Group 1) and sublingual methylcobalamin (Group 2). Group 1 included 29 (9.3%) patients, and Group 2 included 283 (90.7%) patients, with 56 (18%) patients in Group 2 undergoing treatment for childhood cancer. The sublingual methylcobalamin protocol consisted of 1 puff (500 μg) daily for children under 8 years of age and 2 puffs (1000 μg) daily for those 8 years and older, administered for 1.5 months and then three times weekly for an additional 1.5 months. Results: The mean ages in Groups 1 and 2 were 10.07 ± 6.05 years (range, 1–17 years) and 7.43 ± 5.86 years (range, 0.1–17 years), respectively. The female/male ratio was 19/10 in Group 1 and 145/138 in Group 2. The most common diagnoses were anemia (72, 22.9%), cancer (56, 18.0%), and hemangioma (40, 12.7%). The median serum levels of vitamin B12 in Group 1 were 177 ng/L before treatment, 447 ng/L after 1.5 months, and 321.5 ng/L after 3 months. In Group 2, the levels were 172 ng/L before treatment, 438 ng/L after 1.5 months, and 360 ng/L after 3 months. There were no significant between-group differences. Both groups showed a statistically significant increase in levels above 300 ng/L. Discussion: Sublingual methylcobalamin, a noninvasive treatment option, was as effective as intramuscular cyanocobalamin. This study is to compare the standard intramuscular protocol with a new dosing regimen for sublingual methylcobalamin. This study showed that it is also useful for children to hold the spray in their mouths for 1 min and avoid food intake for the next 15 min. Full article

Injectable peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists are being increasingly used for the treatment of diabetes. Currently, the most common route of administration is injection, which is linked to patient discomfort as well as being subjected to refrigerated storage and the requirement for efficient supply chain logistics. Buccal and sublingual routes are recognized as valid alternatives due to their high accessibility and easy administration. However, there can be several challenges, such as peptide selection, drug encapsulation, and delivery system design, which are linked to the enhancement of drug efficacy and efficiency. By using hydrophobic polymers that do not dissolve in saliva, and by using neutral or positively charged nanoparticles that show better adhesion to the negative charges generated by the sialic acid in the mucus, researchers have attempted to improve drug efficiency and efficacy in buccal delivery. Furthermore, unidirectional films and tablets seem to show the highest bioavailability as compared to sprays and other buccal delivery vehicles. This advantageous attribute can be attributed to their capability to mitigate the impact of saliva and inadvertent gastrointestinal enzymatic digestion, thereby minimizing drug loss. This is especially pertinent as these formulations ensure a more directed drug delivery trajectory, leading to heightened therapeutic outcomes. This communication describes the current state of the art with respect to the creation of nanoparticles containing peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists, and theorizes the production of mucoadhesive unidirectional release buccal tablets or films. Such an approach is more patient-friendly and can improve the lives of millions of diabetics around the world; in addition, these shelf-stable formulations ena a more environmentally friendly and sustainable supply chain network. Full article

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation. Full article

Benzodiazepines such as diazepam, lorazepam and midazolam remained the mainstay of treatment for acute repetitive seizures (ARS). The immediate care for ARS should often begin at home by a caregiver. This prevents the progression of ARS to prolonged seizures or status epilepticus. For a long time and despite social objections rectal diazepam gel remained only FDA-approved rescue medication. Intranasal administration of benzodiazepines is considered attractive and safe compared with rectal, buccal and sublingual routes. Intranasal delivery offers numerous advantages such as large absorptive surface area, bypass the first-pass metabolism and good patient acceptance as it is needle free and painless. Recent clinical studies have demonstrated that diazepam nasal spray (NRL-1; Valtoco^®, Neurelis Inc.,San Diego, CA, USA) showed less pharmacokinetic variability and reliable bioavailability compared with the diazepam rectal gel. Diazepam nasal spray could be considered as a suitable alternative for treating seizure emergencies outside the hospital. This review summarizes the treatment options for ARS and findings from clinical studies involving intranasal diazepam for treating seizure emergencies. Full article

Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there has been no way to relieve these symptoms. This study’s aim was to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin (STZ)-induced diabetes model, the dry mouth condition was established as a model. Here, rats were treated with water or IXD through the sublingual spray, and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na⁺/H⁺ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than in each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes, glutathione assay (GSH: GSSG) ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx), were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia. Full article

(1) Background: Vitamin D deficiency is an important public health concern and supplementation is common for this deficiency. Many different modes of delivering supplementation have been proposed in order to enhance absorption and utilization. The present review compared the efficacy of vitamin D₃ buccal spray against other forms of supplementation delivery. (2) Methods: The protocol was registered at PROSPERO (CRD42019136146). Medline/PubMed, CENTRAL and clinicaltrials.gov were searched from their inception until September 2019, for randomized controlled trials (RCTs) that compare vitamin D₃ delivery via sublingual spray against other delivery methods. Eligible RCTs involved humans, of any age and health status, published in any language that evaluated changes in plasma 25(OH)D concentrations. Three reviewers independently extracted data, assessed risk of bias (RoB) and the quality of the trials. (3) Results: Out of 9759 RCTs, four matched the predefined criteria. Intervention duration ranged from 30 days to 3 months whereas vitamin D₃ dosage ranged between 800 and 3000 IU/day. One RCT advocated for the superiority of buccal spray in increasing plasma 25(OH)D concentrations, although several limitations were recorded in that trial. The rest failed to report differences in post-intervention 25(OH)D concentrations between delivery methods. Considerable clinical heterogeneity was observed due to study design, intervention duration and dosage, assays and labs used to perform the assays, population age and health status, not allowing for synthesis of the results. (4) Conclusions: Based on the available evidence, delivery of vitamin D₃ via buccal spray does not appear superior to the other modes of delivery. Future RCTs avoiding the existing methodological shortcomings are warranted. Full article

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 (C_max = 18.5 ng/mL) and CBD (C_max = 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: C_max = 24.5 ng/mL; CBD: C_max = 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. Full article