The influence of the route of drug administration on the metabolic profile of trenbolone in doping control urine samples.

Preliminary evaluation of the effects of cannabidiol via buccal administration, with or without oral carprofen, in alleviating osteoarthritis-associated pain in dogs

Progress towards a prodrug/enzyme intranasal delivery system for rapid prevention/reversal of seizure emergency.

Exploring new buccal films based on hydroxyethyl cellulose and Linecaps® combination for the pediatric delivery of hydrophobic molecules.

Molecularly designed deep eutectic solvents based on choline for site-specific delivery of luteolin in the oral cavity.

Nisin, a food preservative lantibiotic produced by Lactococcus lactis, exhibits potent antimicrobial activity against a wide range of Gram-positive pathogens, including antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). This study explores the development of a novel nano drug delivery platform comprising nisin-loaded niosomes, formulated via microfluidic mixing, and integrated into fast-dissolving oral films for targeted buccal administration. Microfluidic synthesis enabled the precise control of critical parameters including the flow rate ratio, surfactant composition, and lipid concentration, resulting in uniform niosomal vesicles with optimal size distribution (100–200 nm), low polydispersity index, and high encapsulation efficiency. Span 40 and Span 60 were employed as non-ionic surfactants, stabilized with cholesterol to improve bilayer rigidity and drug retention. The encapsulated nisin demonstrated improved physicochemical stability over time and protection against proteolytic degradation, thus preserving its antimicrobial potency. The niosomal suspensions were subsequently incorporated into polymer-based oral films as a final dosage form composed of polyvinyl alcohol (PVA) as the primary film-forming polymer, polyethylene glycol 400 (PEG400) as a plasticizer, and sucralose and mint as a sweetener and flavoring agent, respectively. A disintegrant was added to accelerate film dissolution in the oral cavity, facilitating the rapid release of niosomal nisin. The films were cast and evaluated for thickness uniformity, mechanical properties, disintegration time, surface morphology, and drug content uniformity. The dried films exhibited desirable flexibility, rapid disintegration (<30 s), and consistent distribution of nisin-loaded vesicles. In vitro antimicrobial assays confirmed that the bioactivity of nisin was retained post-formulation, showing effective inhibition zones (16 mm) against Bacillus subtilis. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments. Physicochemical characterization of the niosomes and niosome films was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to evaluate thermal stability and scanning electron microscopy (SEM) to assess surface morphology. In vitro peptide release studies demonstrated sustained release from both niosomal suspensions and film matrices, and the resulting data were further fitted to established kinetic models to elucidate the underlying drug release mechanisms. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments.

Opioids are widely used in the management of acute postoperative pain after thoracic surgery. Buprenorphine (BUP), though discovered as an analgesic, with robust evidence supporting its efficacy for this purpose, and possessing important safety advantages compared with commonly used full agonist opioids, is currently rarely used for acute pain management. To assess feasibility of implementing buccal BUP as part of a multimodal analgesia strategy, and to conduct an exploratory comparison of pain outcomes between patients receiving buccal BUP in addition to standard postoperative pain management, and patients receiving standard postoperative pain management alone. Retrospective cohort. Veterans Health Administration. In this single-center, retrospective cohort study of patients undergoing minimally invasive lung surgery, we assessed feasibility of buccal BUP administration for perioperative pain management, and conducted an exploratory analysis of pain outcomes in 29 patients, a subset of which received perioperative buccal BUP. Buccal BUP is feasible, safe, and is associated with improved pain outcomes after thoracic surgery. This retrospective review within a relatively homogenous population lacks a randomization process and size to address bias and confounding. Further study is needed to confirm any identified associations. We did not assess long-term outcomes, such as function and persistent opioid use. We are not aware of prior study of the buccal formulation of BUP for acute pain management. In this retrospective cohort study of largely opioid-naive patients undergoing thoracic surgery, buccal BUP was feasible, safe, and was associated with reduced pain postoperatively.

This study focused on addressing the efficacy of midazolam in the treatment of acute convulsions in children and its effects on convulsive brain tissue injury. A total of 124 children with acute convulsions were separated into the control group and the observation group according to the random number table method. Children in the control group received intravenous injection therapy with diazepam (0.3-0.5mg/kg); those in the observation group received midazolam buccal mucosa administration treatment (different doses for different age groups). The total effective rate of treatment and adverse reactions were observed. The number of children whose convulsions were controlled within 1, 3, and 5 minutes after medication, the time to initial convulsion control, the number of children who experienced recurrence within 10 minutes after control, and the time to recurrence control were recorded. Juvenile (21-day-old) Sprague-Dawley rats were separated into blank control, model, low-dose midazolam, medium-dose midazolam, and high-dose midazolam groups. Rats in the midazolam groups were injected intraperitoneally with different doses of midazolam. The convulsive model rats were prepared by intraperitoneal injection of pentylenetetrazol, and the emergence time and duration time of convulsions were recorded. The convulsion grade of rats was evaluated. The rats were euthanized, and their brain tissues were taken. The pathological morphological changes in the brain tissues were observed, and glial fibrillary acidic protein (GFAP) and gamma-aminobutyric acid (GABA) expression levels in the brain tissues were tested. The observation group demonstrated a higher total effective treatment rate, a greater number of children whose convulsions were controlled within 3 and 5 minutes of treatment, a shorter average time to convulsion control, a lower recurrence rate within 10 minutes after initial control, a shorter time to control recurrent convulsions, and a lower incidence of adverse reactions compared to the control group. Convulsive model rats that received medium- and high-dose midazolam displayed prolonged emergence time of convulsions, shorter duration, and lower convulsion grade. In convulsive model rats, the nucleus of hippocampal neurons was deeply stained and showed pyknosis; the arrangement of neurons was disordered; the cells were loose and edematous. In the convulsive model, rats received medium- and high-dose midazolam, and the neuron pyknosis and cell oedema were alleviated. In the hippocampus of convulsive model, rats received high-dose midazolam, GFAP expression levels were reduced, and GABA expression levels were raised (p < 0.05). For children with acute convulsions, midazolam buccal mucosa administration can rapidly control convulsive seizures and reduce recurrence rates with high safety. High-dose midazolam can ameliorate brain tissue injury in convulsed rats, reduce GFAP expression levels in hippocampal tissue, and increase GABA expression levels.

Janus LAAM-loaded electrospun fibrous buccal films for treating opioid use disorder.

Purpose: The objective of this research was to compare the pain-reducing effects of two topical anesthetic agents, 10% atomized lidocaine spray and an EMLA, cream before needle injection applied at different time intervals using parameters of visual analog scale (VAS) score and heart rate (HR). Methods: The randomized split-mouth study included 30 patients (17 boys, 13 girls) aged 8.22 ± 1.8 years. The application of atomized lidocaine spray or cream was randomly used in the maxillary second premolar region. The parameters were measured prior to and following each needle insertion after being applied for 10, 30, 60, and 120 sec. Paired t-test and independent t-test were used for statistic analyses. Results: Compared with the first applications (10 s), atomized lidocaine and EMLA cream applications significantly decreased scores of VAS at the 30 and 120 s applications, respectively. Despite atomized lidocaine showing an early effect compared with EMLA, there were no significant differences in VAS scores between the atomized lidocaine and EMLA cream at the 60 and 120 s measurements. Although HR significantly increased at first anesthetic administration with the atomized lidocaine spray, HR significantly decreased at 30 and 120 s administrations. Conclusions: Atomized 10% lidocaine-based topical anesthetics significantly reduced pain more rapidly and better than EMLA from needle pricks in the buccal mucosa. Therefore, atomized lidocaine topical anesthesia could be used as a substitute for EMLA cream prior to buccal anesthetic administration. On the other hand, further comprehensive studies are required to explore the effects of several doses of atomized lidocaine in various areas of the oral cavity.

Devices to overcome the buccal mucosal barrier to administer therapeutic peptides.

Orally disintegrating films based on pullulan and HPMC with carbopol-coated mucoadhesive nanoparticles for dual-pattern drug release.

Both local and systemic medication delivery benefit greatly from the sublingual and buccal modes of administration. They have shown to be a successful substitute for the conventional oral route, particularly in situations requiring a quick commencement of action. Via venous drainage to the superior vena cava, drugs can enter the systemic circulation quickly and directly. They are therefore helpful for individuals who have trouble swallowing as well as for medications that are highly cleared by the liver or degraded in the gastrointestinal system. Traditionally, medications that are delivered through the buccal and sublingual channels are made in three different dose forms: liquid (such as sprays and drops), semi-solid (such as gels), and solid (such as pills, wafers, films, and patches). Physiological variables frequently influence conventional dose forms, which might decrease the formulation's interaction with the mucosa and result in unexpected medication absorption. Many formulation development advancements have been made to enhance medication absorption and retention in the buccal and sublingual areas. The physiological factors influencing buccal and sublingual drug delivery as well as developments in nanoparticulate drug delivery techniques for sublingual and buccal administration will be the main topics of this review. It also discusses about the clinical development pipeline, which includes formulations that have been authorized and are undergoing clinical studies.

Introduction: Propranolol Hydrochloride is a beta-blocker used to treat various cardiovascular conditions. The goal is to enhance the drug's bioavailability and provide a controlled release system suitable for buccal administration. Objectives: The main objectives are to develop a stable buccal emulgel formulation using PHCL and gellan gum, and to evaluate this formulation Methods: PHCL was formulated into various buccal emulgel using gellan gum and different concentrations of oleic acid. The formulations were assessed for organoleptic properties, drug content, pH, viscosity, spreadability, and extrudability. The in vitro drug release was tested, and the optimized formulation was subjected to ex vivo drug release and stability studies. Results: The study investigates the formulation and evaluation of Propranolol HCL emulgel, focusing on drug release and permeability properties. Various formulations (F1-F6) were prepared and tested for in vitro drug release, ex vivo permeability, and stability. The F5 formulation demonstrated superior drug release and permeability, achieving 91.16% drug permeability at 4 hours, compared to 75.48% for the F1 formulation. In vitro release data were analyzed using different kinetic models, with the F5 formulation showing the highest correlation with the Zero-order model, indicating a consistent drug release rate. Stability tests conducted at 40°C and 75% relative humidity confirmed the physical stability of the emulgel. Conclusion: A buccal emulgel was formulated of PHCL using gellan gum. The optimized F5 formulation showed promising results in terms of drug release and stability, making it a potential candidate for further development and scale-up for buccal delivery of PHCL

Peptides represent a rapidly expanding class of drugs with broad therapeutic potential. However, due to their large molecular weight and susceptibility to degradation in the gastrointestinal tract, most peptide drugs are administered via subcutaneous injections. Despite extensive research, a painless broad delivery platform for these drugs is still lacking. Recently, an octopus-inspired buccal patch has shown promise in addressing this challenge by leveraging a synergistic combination of mechanical stretching and permeation enhancers. In this study, the patch and the loaded formulation were optimized to improve ease of use, scalability, and efficacy. Through assessments of mechanical properties, finite element simulations, and ex vivo experiments, we evaluated the effects of patch design and material, as well as the drug matrix composition and the formulation preparation methods on the delivery performance. A patch with a>9-fold larger effective surface area, produced via mold casting of medical-grade silicone (shore hardness 50) and loaded with a lyophilized drug matrix, emerged as the most promising system. In beagle dogs, 30-min application of this patch resulted in a 14.6% bioavailability for teriparatide (4118gmol-1), while bioavailability of semaglutide (4114gmol-1) was 9.6 times higher than that of the commercial tablet. This work showcases how systematic optimization of this technology can improve and simplify the buccal administration of macromolecular drugs, facilitating the clinical translation of this non-invasive dosage form.

Efavirenz (EFV) is a widely utilized antiretroviral agent in HIV/AIDS therapy that is known for its efficacy but is also associated with various side effects. For improved drug delivery, buccal administration offers a promising alternative by allowing the drug to enter the systemic circulation directly through the oral mucosa, bypassing the gastrointestinal tract and first-pass metabolism. This study explored the interaction between EFV and different polymers through molecular docking, revealing a strong binding affinity to Pluronic®F-127 (-2.1kcal/mol). EFV was formulated into nanocrystals (EFV-NC) using Pluronic®F-127 as the stabilizer, characterized by an average particle size of 174.83 ± 15.21nm, a narrow size distribution (PDI of 0.15 ± 0.013), and good stability (zeta potential of -22.27 ± 1.12mV). FTIR and XRD analyses revealed polymer-induced alterations in the crystalline structure of the EFV. The EFV-NC formulation enhanced the solubility (up to 400µg/mL) and achieved 89.58 ± 4.01% drug release within 24h, following the Higuchi model kinetics for controlled release. EFV-NC-loaded dissolving microneedles (EFV-NC-DMN) demonstrated robust mechanical properties, efficient tissue penetration, and minimal moisture absorption. Ex vivo and in vivo studies revealed that compared with oral EFV, EFV-NC-DMN provided a relative bioavailability of 137.40%, with higher plasma concentrations and prolonged release, highlighting its potential for superior HIV/AIDS management via buccal administration and improved therapeutic outcomes.

Cilostazol (CTZ), is a BCS class II drug with limited bioavailability. In the current study, orally disintegrating tablets (ODTs) for buccal delivery of CTZ were prepared by two methods; lyophilization (Lyo-ODTs) and direct compression (DC-ODTs). All CTZ-ODTs were evaluated for in vitro disintegration time (DT) and wetting time (WT) tests, in vitro dissolution. Scanning electron microscopic (SEM) analysis was performed for the selected Lyo-ODT-7 and DC-ODT-2. Lyo-ODT-7 composed of aerosil® 200 and PEG 4000 acquired the shortest DT (13.00 ± 0.14) and WT (33.00 ± 0.26) among the prepared ODTs. It also showed a 2.3 fold significantly enhanced dissolution profile at an early time point (5 min) that was maintained till 1 h, in simulated saliva fluid (pH ∼ 6.8), compared to Pletaal® IR tablets (p < 0.0001). SEM analysis revealed the remarkable porosity of Lyo-ODT-7, confirming its successfully enhanced disintegration and dissolution. Lyo-ODT-7 showed significantly enhanced pharmacokinetic parameters with a 3.5 and 3.6 fold increase in Cmax (p = 0.0493) and AUC0-24 (p = 0.0470), respectively compared to Pletaal® IR tablets. The relative bioavailability of CTZ after buccal administration of Lyo-ODT-7 to rats was 364.45%, compared to the market oral IR tablets; Pletaal®. The enhanced bioavailability imposes the successful oromucosal absorption of CTZ via buccal delivery of Lyo-ODT-7. Our study demonstrated that Lyo-ODT-7 could represent a favorable buccal dosage form for patients with intermittent claudication, suffering from dysphagia. It can also be used in cases of acute cerebral or myocardial infarction due to its significantly enhanced rate and extent of absorption. It is considered a promising approach for buccal delivery of BCS class II active pharmaceutical ingredients (APIs) suffering from solubility problems and hepatic first pass effect.

This research aimed to develop mucoadhesive buccal films incorporating nanostructured lipid carriers (NLCs) loaded with triamcinolone acetonide (TN-films). A Box–Behnken design was employed as a systematic approach to optimize the formulation. Key components of the NLCs—spermaceti, soybean oil, and polysorbate 80—were considered independent variables. The NLCs were prepared and size-reduced using a combination of hot homogenization and ultrasonic probe techniques. Films were cast using hydroxypropyl methylcellulose (HPMC) as the film-forming agent. The TN-films were characterized based on weight, thickness, tensile strength, elongation at break, contact angle, and surface free energy. Linear regression showed that spermaceti increased film weight and thickness, while polysorbate 80 decreased them. The mechanical strength of the films was primarily influenced by spermaceti; higher concentrations of spermaceti resulted in decreased film strength. Additionally, all independent variables contributed positively to the lipophilicity of the films. The TN-films were found to sustain drug release via a Fickian diffusion mechanism, exhibiting rapid swelling and favorable mucoadhesive properties. Moreover, the TN-films demonstrated superior drug release and permeation to pastes and films loaded with emulsions. These findings suggest that the TN-films represent a promising and effective approach for the buccal delivery of triamcinolone acetonide.

Status epilepticus (SE) is a life-threatening state that needs rapid and adequate treatment. Benzodiazepines (BZD) are used as a first-line treatment for SE, and if the desired effect is not achieved, second-line antiseizure medications are used. To investigate whether the treatment with BZDs is performed adequately in patients with different subtypes of SE requiring second-line ASM treatment and, if not, to identify the factors influencing the suboptimal treatment. This is a retrospective single centre study from the patient register of Tampere University Hospital including patients over 16 years of age with a diagnosis of SE, seizure or epilepsy and who received intravenous (IV) ASM during a one-year period in 2015. Treatment was considered to be suboptimal if it was not in line with the latest European, Finnish or American guidelines. In total, 109 episodes were registered. The largest group was that with convulsive SE with 56 episodes, followed by postictal with 23 episodes, nonconvulsive status epilepticus (NCSE) with 22 episodes, and focal awareness SE (FASE) with eight episodes. Overall, in 77 % of the episodes, BZDs were administered, and in 43 % of the episodes, treatment was in line with guidelines. In the NCSE group, BZD was administered less often and was less often in line with the guidelines than in the CSE group (27.3 % vs. 89.3 %, p < 0.001 and 4.5 % vs. 55.4 %, p < 0.001). For FASE episodes, the concordance with the guidelines was low. After IV administration, the mean BZD dose was lower than that after buccal administration of midazolam (2.1 mg vs. 8.7 mg) or after rectal administration of diazepam (4.5 mg vs. 10.0 mg). Lorazepam was administered only via the IV route, with mean dosage of 2.6 mg. Clinical characteristics did not influence the dosing of BZDs. BZDs were both underdosed and underused for all subtypes of SE. In particular, their use for NCSE was infrequent and suboptimal. The divergence from the guidelines was influenced especially by low IV dosages.

Introduction. Modern pharmaceutical development enables to introduce into practice more than ever new active ingredients delivery systems and forms enhancing actives activity compared to traditional approach (methods). A nowadays pace of life often providing improper feeding and micronutrients intake imbalance leads to necessary administration of micronutrient additional doses in the form of different pharmacies. Over the last years vitamins and minor nutrient elements spray forms are becoming more attractive for introduction into pharmaceutical practice. These dosage forms are characterized by the production availability, usability, easy dosage and sufficiently high bioavailability for both normal patients and ones having gastrointestinal tract diseases and other problems connecting with the food consumption and digestion.Text. Drug delivery by oral mucosa attracts more attention due to its potential advantages compared to other methods. Until recently this administration way was considered mainly for topical application. However, in recent years number of developments connecting with oral cavity application as a portal for delivery of drugs active ingredients, vitamins and micronutrients into systemic blood has kept steadily growing. Diverse forms of oral drugs for sublingual and buccal administration have been developed by many scientific and clinical teams. Spray forms among them are of particular interest as the most economically viable and easy to use. Most of these developments deal with vitamins D and B12, which arises from the acutest problems of their deficiency among global population, on the one hand, and low bioavailability due to negative effects by dietary intake, gastrointestinal tract health condition and other factors, on the other hand. Other micronutrients such as thiamin, niacin, pyridoxin, ascorbic acid, coenzyme Q and iron are examined and launched into the market in an oral spray form for sublingual application.Conclusion. The current results of development and comparison study of micronutrients oral forms, in particular, randomized controlled trial data indicate a sublingual administration efficiency which either is similar to or exceeds traditional administration ways.