Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Spray-Dried Chitosan Hydrogel Particles as a Potential Delivery System for Benzydamine Hydrochloride.

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.

Phase IV study on the use of benzydamine mouthwash in radiation-induced oral mucositis in patients with head and neck cancer.

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.

The Effect of Topical Benzydamine Hydrochloride and Cuff Pressure Monitorization on Postoperative Sore Throat Due to Intubation.

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 cmH2O, 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 cmH2O after intubation with a manometer and maintained at this pressure range throughout the operation. There was no beneficial effect of BH.

Novel Sprayable Thermosensitive Benzydamine Hydrogels for Topical Application: Development, Characterization, and In Vitro Biological Activities.

Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.

Benzydamine plays a role in limiting inflammatory pain induced by neuronal sensitization.

Benzydamine is an active pharmaceutical compound used in the oral care pharmaceutical preparation as NSAID. Beside from its anti-inflammatory action, benzydamine local application effectively reliefs pain showing analgesic and anaesthetic properties. Benzydamine mechanism of action has been characterized on inflammatory cell types and mediators highlighting its capacity to inhibit pro-inflammatory mediators' synthesis and release. On the other hand, the role of benzydamine as neuronal excitability modulator has not yet fully explored. Thus, we studied benzydamine's effect over primary cultured DRG nociceptors excitability and after acute and chronic inflammatory sensitization, as a model to evaluate relative nociceptive response. Benzydamine demonstrated to effectively inhibit neuronal basal excitability reducing its firing frequency and increasing rheobase and afterhyperpolarization amplitude. Its effect was time and dose-dependent. At higher doses, benzydamine induced changes in action potential wavelength, decreasing its height and slightly increasing its duration. Moreover, the compound reduced neuronal acute and chronic inflammatory sensitization. It inhibited neuronal excitability mediated either by an inflammatory cocktail, acidic pH or high external KCl. Notably, higher potency was evidenced under inflammatory sensitized conditions. This effect could be explained either by modulation of inflammatory and/or neuronal sensitizing signalling cascades or by direct modulation of proalgesic and action potential firing initiating ion channels. Apparently, the compound inhibited Nav1.8 channel but had no effect over Kv7.2, Kv7.3, TRPV1 and TRPA1. In conclusion, the obtained results strengthen the analgesic and anti-inflammatory effect of benzydamine, highlighting its mode of action on local pain and inflammatory signalling.

The present and the future of benzydamine: expert opinion paper.

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.

A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy.

Background: Concurrent chemoradiation (CCRT) has been the standard treatment for organ preservation or locally advanced head and neck cancer (LAHNC). Radiation-induced oral mucositis (RIOM) is an important treatment-limiting toxicity. Benzydamine hydrochloride was recommended to prevent oral mucositis. Povidone-iodine had also been adopted to use as an oral rinse to prevent mucositis. Objective: This study compared the efficacy between benzydamine hydrochloride and 0.1% povidone-iodine to prevent RIOM in HNC patients who received concurrent chemoradiotherapy. Methods: We conducted a randomized control study in HNC patients receiving CCRT with curative intent. The stratification factors were primary site of disease, treatment modality, chemotherapy regimen, and schedule. The primary outcome was RIOM assessed by Oral Mucositis Assessment Scale (OMAS). Secondary outcomes included RIOM assessed by NCI-CTCAE, use of analgesic, antibiotics and anti-fungal drugs, hospitalization, and participant satisfaction. Results: There were 83 participants recruited for this study with 71 completing the trial. Demographic characteristics were well-balanced between both arms. The univariate regression analysis revealed that povidone-iodine correlated with less RIOM compared to benzydamine hydrochloride (coefficient -2.25, 95% CI -4.37 to -0.012, p-value 0.03). The incidence of grade III-IV CTCAE RIOM during the study period was 51.4% with benzydamine hydrochloride compared to 26.5% with 0.1% povidone iodine (p-value 0.032). The peak incidence of grade III-IV CTCAE RIOM occurred in the 7th week of treatment (40.5% vs. 11.8%, p-value 0.01). This indicated the efficacy of povidone-iodine to prevent severe RIOM which usually most severity in the last week of CCRT treatment. The multivariate analysis revealed that the CCRT setting (definitive vs. adjuvant) and gargling agents (povidone-iodine vs. benzydamine hydrochloride were the factors associated with RIOM. Conclusion: This study demonstrated higher efficacy of 0.1% povidone-iodine gargle than benzydamine hydrochloride in mucositis prevention.

Benzydamine-An Affordable Over-the-Counter Drug with Psychoactive Properties-From Chemical Structure to Possible Pharmacological Properties.

Benzydamine is a non-steroidal anti-inflammatory drug with distinct pharmacological properties from other compounds in the same therapeutic class. The differences are structural and pharmacological in nature; the anti-inflammatory mechanism is not strictly explained by the ability to interfere with the synthesis of prostaglandins. The compound is used strictly in local inflammatory diseases (inflammation in the oral and vaginal mucosa). In addition to the therapeutic indications found in the summary of product characteristics (SPC), the compound is used, in high doses, as a psychotropic substance for oral administration, having similar properties to lysergic acid diethylamide (LSD). As an over-the-counter (OTC) compound, it is easy to obtain, and the consequences of using it for purposes other than those assumed by the manufacturer raise various concerns. The reasons are related to the pharmacodynamic and pharmaco-toxicological properties, since neither the mechanism of action nor the possible side effects that would result from systemic consumption, in high doses, even occasionally, have been fully elucidated. The present review aims to analyze the pharmacodynamic properties of benzydamine, starting from the chemical structure, by comparison with structurally similar compounds registered in therapy (as an anti-inflammatory or analgesic) or used for recreational purposes.

Sumac-rose water mouthwash versus benzydamine to prevent radiation-induced oral mucositis in head and neck cancers: a phase II randomized trial.

BACKGROUND: Radiation-induced oral mucositis (OM) largely impairs the quality of life (QoL) of patients with head and neck cancer (HNC). Few choices with limited efficacy are available to prevent this adverse effect. This randomized trial was conducted to compare the efficacy of benzydamine (standard) and a new combination (sumac and rose water) in preventing radiation-induced OM. METHODS: This was a phase II, triple-blind, active-controlled, randomized trial. The primary endpoint was OM, and the secondary endpoints were oral pain and QoL. Besides, the possible variables defining the outcomes were analyzed using the chi-squared test (univariate analysis) and binomial regression model (multivariate analysis). RESULTS: Sumac-rose group had fewer high-grade OM (33% vs. 63%, odds ratio [OR] 0.28, 95% confidence interval [CI 95%] 0.08-0.93, P = 0.03) and better QoL (P < 0.05). Multivariate analysis confirmed these findings. Sumac-rose rinsing could also postpone the start of oral pain (hazard ratio [HR] 0.02, CI 95% 0.001-0.32, P = 0.001) and high-grade OM (HR 0.28, P = 0.03) compared with benzydamine. CONCLUSIONS: The sumac-rose group had a lower OM rate and grade and higher QoL than the benzydamine group. In addition, the experimental group developed high-grade OM and oral pain later during the radiotherapy course. Further studies need to be conducted to assess the role of sumac and rose water in reducing grade 3-4 mucositis in patients who undergo chemoradiation for head and neck cancer.

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma / 医学前沿

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Clinicians' experience with topical benzydamine and morphine for the management of oral mucositis: adverse effects and barriers.

INTRODUCTION: Among the evidence-based agents outlined in the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) mucositis guidelines, benzydamine and morphine are advised for the management of oral mucositis (OM) in certain cancer patients. This study is aimed to collect information from a group of highly experienced healthcare professionals in the field of oral mucositis about their clinical experience with these agents. METHODS: A survey questionnaire about the clinical experience with topical benzydamine and morphine to manage oral mucositis and their related adverse effects (AEs) was electronically distributed to the members of the Mucositis Study Group of MASCC/ISOO. RESULTS: Eighty-eight entries were recorded (response rate 25%), and 54 entries submitted complete questionnaires about the drug-related AE (completion rate 65%) and were used for the data analysis. Of the respondents, 44% and 27.7% prescribed benzydamine and morphine to manage their patients' oral mucositis, respectively. Lack of availability in the respondent's country was the common reason for not prescribing benzydamine and morphine (18.9% and 5.4%, respectively); however, a large portion of the respondents indicated that 'another reason' stopped them from prescribing these agents (51.3% and 73%, respectively). AEs to benzydamine or morphine were observed by 25.9% and 12.9% of respondents, respectively, with mild numbness and tingling as the most common drug-related AE for both agents. CONCLUSION: The use of topical benzydamine and morphine for the management of OM varies between countries. While relatively common, the AEs related to these agents are mild. Mitigating the barriers for prescribing them may increase their use.

International Delphi-based consensus on the appropriate use and effect of Benzydamine hydrochloride in the treatment of sore throat.

BACKGROUND: Benzydamine hydrochloride is a locally-acting Non-Steroidal Anti-Inflammatory Drug (NSAID) with combined local anesthetic and analgesic properties, indicated for the symptomatic relief of pain in acute sore throat. The aim of this study was to obtain an European Consensus among pharmacists, general practitioners and pediatricians on the appropriate use of benzydamine hydrochloride in the treatment of sore throat. METHODS: The authors developed a Delphi questionnaire organized into 15 statements focused on 4 topics: the mechanism of action of benzydamine, the benzydamine treatment in an adult patient and in a pediatric patient, and the advantages of benzydamine over other topical treatments. The survey was administered to a panel of to 320 participants including general practitioners, pediatricians, and pharmacists from 6 European countries (Italy, Germany, Portugal, Romania, Russia, and Spain), who rated their level of agreement or disagreement with each statement on a 6-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with each statement. RESULTS: Panelists' agreement on statements was very high. Consensus was reached for all 15 statements in the Delphi survey, with more than 98% positive agreement on topic 4, suggesting a shared view among European healthcare professionals (HCPs) about the advantages of benzydamine over other topical treatments. A strong consensus (> 99%) was reached for all the statements of topic 1 regarding the mechanism of action of benzydamine, except for its anesthetic properties (79%). Strong agreement was reached for all statements in topics 2 and 3 regarding the treatment of acute sore throat symptoms in the adult and pediatric patient, except for one on the efficacy of benzydamine in preventing post-operative sore throat, for which it was 67%. CONCLUSION: Because all relevant publications on benzydamine are dated and there are no recommendations on its use for the symptomatic treatment of sore throat in European guidelines, this Delphi-based international consensus may be important in reinforcing the appropriate use and effect of benzydamine in the treatment of sore throat among health care professionals.

[Efficiency of benzydamine use in treatment of URTI (including COVID-19) in child patients]. / Klinicheskie rezul'taty kuratsii patsientov detskogo vozrasta s porazheniem respiratornogo trakta pri ostrykh respiratornykh virusnykh infektsiyakh (vklyuchaya COVID-19).

THE AIM: Share with healthcare practitioners personal experience of using benzydamine spray (Oralsept) in pediatric practice; present a clinical case, which, according to the author, can help doctors optimize approaches to the treatment of patients with acute respiratory viral infections (including COVID-19), thereby improving the quality of life of pediatric patients.

IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride, benzydamine hydrochloride with chitosan, calcium hydroxide and chlorhexidine medicaments: An ELISA study.

The aim of the present study was to evaluate IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride (BNZ), BNZ with chitosan, calcium hydroxide (CH) and chlorhexidine (CHX) medicaments. Half maximal inhibitory concentrations (IC50) were assessed on THP-1, Saos-2, and CRL-2014 cells using MTT assay. THP-1 cells were differentiated into macrophages with phorbol12-myristate13-acetate and activated with lipopolysaccharide. IL-1ß, IL-6 and TNF-α levels in supernatants were determined using enzyme-linked immunosorbent assay (ELISA). The data were examined with one-way ANOVA and Tukey's multiple comparison test (p=0.05). At the selected concentrations, the cell viability was higher than 50% for chitosan and CH, whereas CHX presented lower IC50 values than BNZ and BNZ+chitosan. According to ELISA results, the lowest IL-1ß, IL-6 and TNF-α values were observed with BNZ+Chitosan 50 µg/mL and BNZ 50 µg/mL. BNZ+chitosan 50 µg/mL combination has revealed promising anti-inflammatory effects. Nevertheless, these findings need to be examined in clinical conditions.

Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners.

BACKGROUND: Benzydamine for oromucosal use is indicated in the relief of pain and irritation of the mouth and throat. It is an indazole derivative, non-steroidal anti-inflammatory drug, with combined local anesthetic and analgesic properties, and antiseptic activity, marketed under the brand name "Tantum Verde". The aim of this study was to explore knowledge and prescriptive/advising attitudes among general practitioners (GPs) and pharmacists (PHs) with regard to the topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, with a focus on benzydamine. These findings could be important to increase awareness on benzydamine efficacy in sore throat and stomatological conditions, and to reinforce knowledge on the characteristics of benzydamine and its mechanisms of action among healthcare professionals (pediatricians, otolaryngologists, oncologists, etc.). MATERIALS AND METHODS: An online questionnaire survey was performed among PHs and GPs in four European countries (Italy, Germany, Russia and Poland). RESULTS: Both GPs and PHs proved to have an excellent knowledge and mastery of the constituents effective against oral symptoms. Among all the principles, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity. It is recommended by about 90% of PHs and prescribed by 80% of GPs, mainly to solve the ailments caused by sore throats and stomatitis, especially for its anti-inflammatory, analgesic and anesthetic characteristics. Also in the pediatric field, benzydamine hydrochloride is recommended: among GPs, a high percentage (about 40%) prescribes it like the remedies based on dichlorobenzyl alcohol-sodium benzoate, which are instead more often recommended by PHs (44% against 37%). CONCLUSION: Although the public has a lot of confidence in this treatment, GPs and PHs do not recommend/prescribe benzydamine as a first-line treatment of sore throat and other irritative/inflammatory conditions of the oropharynx. To increase the knowledge of benzydamine among these healthcare professionals, it would be important to emphasize its characteristics and the different irritative/inflammatory conditions of the oropharynx in which it can be used.

Polyelectrolyte Multilayer Films as a Potential Buccal Platform for Drug Delivery.

The goal of this research was to study the potential of polyelectrolyte multilayers as buccal dosage forms for drug delivery and to investigate how the properties of the drugs impact the overall performance of the delivery system. Multilayer films based on the polyelectrolyte interaction between casein and chitosan were developed using benzydamine, tolfenamic acid and betahistine as model drugs. The samples were characterized for surface pH, moisture content and moisture absorption, swelling behavior and mucoadhesion. Additionally, surface morphology was investigated, as well as the drugs' physical state after incorporation in the multilayer films. The samples proved to be non-irritant (pH was within the physiological range), physically stable (moisture content and moisture absorption below 5%) and mucoadhesive, adsorbing from 60 to 70% mucin. The release behavior corelated to the swelling index profiles of the samples and was strongly dependent on the drug solubility. The developed multilayer films appeared to be an optimum delivery system for sparingly soluble drugs due to the high drug loading achieved.

Casein Microgels as Benzydamine Hydrochloride Carriers for Prolonged Release.

This research aims to investigate the properties of nano- and micro-sized casein hydrogels crosslinked by sodium tripolyphosphate as drug delivery systems. Benzydamine hydrochloride was chosen as a model hydrophilic drug. The gels were synthesized by varying different parameters: casein concentration, casein/crosslinking ratio, and addition of ethanol as a co-solvent. The electrostatic attractive interactions between the casein and the sodium tripolyphosphate were confirmed by FTIR spectroscopy. The particle sizes was determined by dynamic light scattering and varied in the range between several hundred nanometers and several microns. The yield of the gelation process was high for all investigated samples and varied between 55.3% and 78.3%. The encapsulation efficiency of the particles was strongly influenced by the casein concentration and casein/crosslinker ratio and its values were between 4.6% and 22.4%. The release study confirmed that casein particles are useful as benzydamine carriers and ensured prolonged release over 72 h.

Effects of benzydamine and mouthwashes containing benzydamine on Candida albicans adhesion, biofilm formation, regrowth, and persistence.

OBJECTIVES: To assess the effects of benzydamine and mouthwashes (MoWs) containing benzydamine on different stages of Candida albicans biofilm: adhesion, formation, persistence, and regrowth (if perturbed). MATERIALS AND METHODS: C. albicans CA1398, carrying the bioluminescence ACT1p-gLUC59 fusion product, was employed. Fungal cells were exposed for 1', 5', or 15' to 4 different benzydamine concentrations (0.075 to 0.6%) to 2 mouthwashes (MoWs) containing benzydamine and to a placebo MoW (without benzydamine). Treated cells were tested for adhesion (90 min) and biofilm formation (24-h assay). Next, 24- and 48-h-old biofilms were exposed to benzydamine and MoWs to assess regrowth and persistence, respectively. The effects of benzydamine, MoWs containing benzydamine, and placebo on different biofilm stages were quantified by bioluminescence assay and by the production of quorum sensing (QS) molecules. RESULTS: Benzydamine and MoWs containing benzydamine impaired C. albicans ability to adhere and form biofilm, counteracted C. albicans persistence and regrowth, and impaired a 48-h-old biofilm. Some of these effects paralleled with alterations in QS molecule secretion. CONCLUSIONS: Our results show for the first time that benzydamine and MoWs containing benzydamine impair C. albicans capacity to form biofilm and counteract biofilm persistence and regrowth. CLINICAL RELEVANCE: Benzydamine and MoWs containing benzydamine capacity to affect C. albicans biofilm provides an interesting tool to prevent and treat oral candidiasis. Likely, restraining C. albicans colonization through daily oral hygiene may counteract colonization and persistence by other critical oral pathogens, such as Streptococcus mutans, whose increased virulence has been linked to the presence of C. albicans biofilm.