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Frontiers in Oral Health 2023Benzydamine is a compound indicated in the treatment of symptoms of irritation/inflammation of the oropharyngeal cavity, including those associated with pain. Objectives...
OBJECTIVES
Benzydamine is a compound indicated in the treatment of symptoms of irritation/inflammation of the oropharyngeal cavity, including those associated with pain. Objectives of this expert opinion narrative review is to summarize current indicated benzydamine applications and elicit further ones to be explored.
MATERIALS AND METHODS
In this expert opinion paper, evidences underlying the mechanism of action and clinical application of benzydamine are reviewed. Insights are also provided on possible new clinical applications of the drug and new formulations.
RESULTS
Current recognized indications of benzydamine include: relief of symptoms associated with inflammatory conditions of the mouth and oropharynx, symptomatic treatment of gingivitis and stomatitis, oral mucositis induced by chemotherapy and/or radiotherapy and post operative sore throat. In addition, among new applications that need to be explored experts embed: oral lichen planus, burning mouth syndrome, post intubation sore throat, antifungal action and new anticancer target agents induced mucositis.
CONCLUSIONS
Benzydamine is a very versatile compound able to play an auxiliary and adjuvant role in the prevention and treatment of oral cavity/oropharynx disorders. According to experts' opinion there is the need to design clinical trials to highlight novel possible applications of benzydamine and implemented translational analyses to fine-tune patients' selection and open future research scenarios.
PubMed: 37405329
DOI: 10.3389/froh.2023.1191319 -
Supportive Care in Cancer : Official... Dec 2023Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized... (Review)
Review
AIM
Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers.
METHODS
A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy.
RESULTS
A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity.
CONCLUSION
Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.
Topics: Humans; Mucositis; Radiation Oncology; Mouthwashes; Sodium Bicarbonate; Hyaluronic Acid; Stomatitis; Radiation Injuries; Head and Neck Neoplasms; Steroids
PubMed: 38110572
DOI: 10.1007/s00520-023-08185-5 -
Pharmaceutics Jul 2023This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems.
AIM
This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems.
METHODS
Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via H NMR, FTIR, as well as Ellman's test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus.
RESULTS
Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (/) and low cytotoxicity up to 2% (/). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA.
CONCLUSION
Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity.
PubMed: 37514179
DOI: 10.3390/pharmaceutics15071993 -
ACS Omega Nov 2023Aqueous solubility of pharmaceutical substances plays an important role in small molecule drug discovery and development, with ionizable groups often employed to enhance...
Aqueous solubility of pharmaceutical substances plays an important role in small molecule drug discovery and development, with ionizable groups often employed to enhance solubility. Drug candidate compounds often contain ionizable groups to increase their solubility. Recognizing that the electrostatically charged form of the compound is much more soluble than the uncharged form, this work proposes a model to explore the relationship between the p shift of the ionizable group and dissolution equilibria. The model considers three forms of a compound: dissolved-charged, dissolved-uncharged, and aggregated-uncharged. It analyzes two linked equilibria: the protonation of the ionizable group and the dissolution-aggregation of the uncharged form, with the observed p shift depending on the total concentration of the compound. The active concentration of the aggregates determines this shift. The model was explored through the determination of the p shift and intrinsic solubility of specific compounds, such as ICPD47, a high-affinity inhibitor of the Hsp90 chaperone protein and anticancer target, as well as benzoic acid and benzydamine. The model holds the potential for a more nuanced understanding of intrinsic solubility and may lead to advancements in drug discovery and development.
PubMed: 38046347
DOI: 10.1021/acsomega.3c04071 -
Cureus Feb 2024Postoperative sore throat (POST) is the most common discomfort after endotracheal intubation. Damage to the tracheal mucosa caused by inappropriate endotracheal tube...
OBJECTIVE
Postoperative sore throat (POST) is the most common discomfort after endotracheal intubation. Damage to the tracheal mucosa caused by inappropriate endotracheal tube (ETT) cuff pressure has been shown as the major factor. Monitoring the ETT cuff pressure at a certain value reduces this damage. Benzydamine hydrochloride (BH) has proven to be effective on sore throat and studies have shown that it is also effective on POST. In this study, the efficacy of BH and ETT cuff pressure monitoring on POST was evaluated.
MATERIALS AND METHODS
After ethics committee approval 210 patients in the ASA (American Society of Anesthesiologists) I-III risk group undergoing elective surgery were included in the study. Routine anesthesia monitoring, induction, and maintenance were provided. Patients were randomly divided into three groups. Thirty minutes before surgery, the posterior pharyngeal wall was sprayed with BH in group 1 and distilled water in groups 2 and 3. Intraoperatively, the first and second groups were monitored to keep the ETT cuff pressure between 22 and 26 cmHO, while no intervention was performed in the third group. The incidence and severity of postoperative dysphagia, hoarseness, and POST were questioned.
RESULTS
There was no difference between demographic data, and gender was not associated with POST. There was a statistically significant difference between the first and second groups and the third group in terms of all three symptoms questioned (p<0.01). No difference was observed between the first and second groups. Side effect rates were similar. Smoking was not found to be associated with symptoms.
CONCLUSION
The incidence and severity of POST, dysphagia, and hoarseness are reduced when the ETT cuff is inflated with a pressure of 22-26 cmHO after intubation with a manometer and maintained at this pressure range throughout the operation. There was no beneficial effect of BH.
PubMed: 38322097
DOI: 10.7759/cureus.53725 -
Pharmaceutics Mar 2024Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions,...
Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 μm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.
PubMed: 38675121
DOI: 10.3390/pharmaceutics16040460 -
Gels (Basel, Switzerland) Mar 2024Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present...
Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present study are to obtain spray-dried microparticles based on low-molecular-weight chitosan and study their potential application as cargo systems for the orally active drug benzydamine hydrochloride. Three types of particles are obtained: raw chitosan particles (at three different concentrations), cross-linked with sodium tripolyphosphate (NaTPP) particles (at three different chitosan:NaTPP ratios), and particles coated with mannitol (at three different chitosan:mannitol ratios), all of them in the size range between 1 and 10 µm. Based on the loading efficiency and the yields of the formulated hydrogel particles, one model of each type is chosen for further investigation of the effect of the cross-linker or the excipient on the properties of the gel structures. The morphology of both empty and benzydamine hydrochloride-loaded chitosan particles was examined by scanning electron microscopy, and it was quite regular and spherical. Interactions and composition in the samples are investigated by Fourier-transformed infrared spectroscopy. The thermal stability and phase state of the drug and drug-containing polymer matrixes were tested by differential scanning calorimetry and X-ray powdered diffraction, revealing that the drug underwent a phase transition. A drug release kinetics study of the chosen gel-based structures in simulated saliva buffer (pH = 6.8) and mathematical modeling of the process were performed, indicating the Weibull model as the most appropriate one.
PubMed: 38534607
DOI: 10.3390/gels10030189 -
Frontiers in Oncology 2024Oral mucositis (OM) is a main side effect of treatment for head and neck cancer (HNC) and causes severe pain, reduces quality of life, and may interrupt HNC treatment....
INTRODUCTION
Oral mucositis (OM) is a main side effect of treatment for head and neck cancer (HNC) and causes severe pain, reduces quality of life, and may interrupt HNC treatment. This study assessed the activity and feasibility of benzydamine mouthwash in the prevention and treatment of radiation-induced OM in patients with HNC during radiation therapy (RT).
METHODS
This phase IV, international, open-label, single-group study conducted from December 2021 to September 2022. In total, 89 patients were enrolled across seven centers in Hungary and Poland. Patients used benzydamine mouthwash at home two to three times daily. Data were collected during clinical visits at baseline (V0, start of RT) and then weekly for seven visits (V1-V7). The safety population and the modified intention-to-treat (m-ITT) analysis sets contained 89 patients; the per protocol (PP) analysis set contained 67 patients.
RESULTS
The m-ITT set was 80.9% male; mean age was 61.4 years. At baseline, 73.0% of patients had stage T3-T4, 23.6% had stage T1-T2, 61.8% had stage N2-N3, and 34.9% had stage N0-N1. Within the m-ITT population, 33.7% (n=30) responded to treatment (NRS < 5) during the study. The PP set responded similarly (29.9%). Most patients were treatment compliant (n=77; 86.5%). OM severity was assessed using the WHO OM grading scale. No patients had severe mucositis at baseline or V1. At V7, 34.1% had mild mucositis, 45.1% had moderate mucositis, 15.9% had severe mucositis, and 1.2% had life-threatening mucositis. In total, 26 patients (29.2%) developed severe mucositis during the study period (V2-V7). From V1 to V4, one patient reported hospitalization due to mucositis or associated complications, two patients at V5, three patients at V6, and four patients at 7.
DISCUSSION
This was the first study to assess feasibility of a treatment for radiation-induced OM with benzydamine mouthwash in patients with HNC. Treatment compliance suggested that benzydamine was well tolerated in patients with moderate to severe mucositis. Benzydamine's anesthetic and anti-inflammatory properties might have reduced pain, which potentially influenced patients' compliance with RT. Few patients in the study required hospitalization for OM or an associated complication, suggesting that benzydamine might improve healthcare resource utilization.
PubMed: 38469245
DOI: 10.3389/fonc.2024.1345129 -
European Journal of Dentistry Jan 2024The study aimed to develop and test an model to investigate the staining potential of mouth rinses on human enamel, considering alternating intake of black tea and...
OBJECTIVES
The study aimed to develop and test an model to investigate the staining potential of mouth rinses on human enamel, considering alternating intake of black tea and tooth brushing, thus mimicking the situation in the oral cavity more realistically.
MATERIALS AND METHODS
Eight mouth rinses with six different active ingredients (benzydamine hydrochloride [BNZ], polyhexamethylene biguanide hydrochloride [PHMB], chlorhexidine digluconate [CHX], hexetidine gluconate [HEX], octenidine dihydrochloride [OCT] and octenidine dihydrochloride + 2-phenoxyethanol [OCTP]) and concentrations were tested. Sets of six halved human molar crowns were initially pretreated by soaking in artificial saliva (30 min). Afterward, the cyclic treatment was started by soaking in artificial saliva (2 min), staining with black tea (1 min), brushing with toothpaste (5 s), and soaking in the mouth rinse (30 s). Samples were rinsed with distilled water after each treatment step. The cyclic treatment was repeated 30 times, mimicking the consumer behavior after 15 days. Photographic images were taken after 0, 10, 20, and 30 cycles. Color measurements were conducted after each staining and brushing step using a VITA-Easyshade spectrophotometer to determine the difference in lightness ∆L and the total color difference ∆E.
STATISTICAL ANALYSIS
Analysis of variance and post-hoc Tukey test (α = 0.05) were applied.
RESULTS
The new testing model with included brushing sequences allowed to assess the staining behavior on human teeth and provided a clear differentiation between the different investigated products. In detail, up to cycle 10, ΔE values increased for all mouth rinses with each additional cycle number. However, while ΔE values continued to increase for 0.15% BNZ, 0.1% PHMB, and 0.2% CHX between treatment cycle 10 and 30, ΔE values only slightly increased after treatment with 0.08% OCTP, 0.1% OCTP, 0.1% OCT, and 0.1% HEX. After 20 and 30 cycles, significantly less staining was found for 0.08% OCTP, 0.1% OCT, 0.1% HEX as compared to 0.2% CHX, 0.15% BNZ, and 0.1% PHMB ( < 0.05). ΔE-values were significantly lower after treatment with 0.1% OCTP as compared to 0.2% CHX1 and 0.2% CHX2 (p < 0.05).
CONCLUSION
The proposed new methodology was found to be appropriate for assessing the staining progression of mouth rinses over a simulated application period of 15 days. The model allows differentiation of products with different active ingredients and concentrations.
PubMed: 38262467
DOI: 10.1055/s-0043-1777047 -
Journal of Asthma and Allergy 2023Geographic tongue (GT) is a chronic tongue condition triggered by various factors such as immune reactions, allergies, stress, hereditary factors, and nutritional...
INTRODUCTION
Geographic tongue (GT) is a chronic tongue condition triggered by various factors such as immune reactions, allergies, stress, hereditary factors, and nutritional deficiencies. The prevalence of GT in the population ranges from 1% to 3%, and its symptoms can cause discomfort to patients. Spicy foods are popular among Indonesians. Chili is one such food that can cause allergies and trigger GT.
OBJECTIVE
This report highlights the significance of identifying the risk factors associated with symptomatic GT.
CASE
A 19-year-old female patient complained of a rough and sore dorsal tongue for a year, particularly after consuming spicy food. Extra-oral examination revealed dry lips. Intra-oral examination showed red patches with white borders on the dorsal tongue. A complete blood count and allergy test were performed. The eosinophil count was 4%, the total IgE level was 698 IU/mL, and the skin prick test for chili was positive. The diagnosis of chili-induced GT was made.
CASE MANAGEMENT
The patient was advised to avoid chilies, and benzydamine hydrochloride mouthwash was administered. One week after treatment, clinical improvement was observed. Severity decreased on the Geographic Tongue Area and Severity Index (GTASI) from 12 (moderate) to 0.4 (mild). Pain decreased from 6 to 0 on the numerical rating scale (NRS).
CONCLUSION
Management of symptomatic GT includes the avoidance of allergens such as chilies and appropriate pharmacological therapy. The identification of risk factors is required for effective management.
PubMed: 38022749
DOI: 10.2147/JAA.S434177