Effect of Honey-Lemon Spray Versus Benzydamine Hydrochloride Spray on Radiation-Induced Acute Oral Mucositis in Head and Neck Cancer Patients: A Pilot, Randomized, Double-Blind, Active-Controlled Clinical Trial.

Introduction: Oral mucositis (OM) is the most prevalent side effect in patients with head and neck cancer (HNC). It causes an obvious decrease in quality of life (QoL) in these patients, so different medications have been recommended for OM, however, without optimal response. This randomized trial aimed to assess the effects of a honey-lemon spray compared with benzydamine hydrochloride in prevention of radiation-induced OM in patients with HNC. Materials and Methods: Forty-six patients with HNC received external beam radiotherapy for 5 days per week. Patients were randomized to treatment with either benzydamine hydrochloride spray or honey-lemon spray for 5 weeks and continued for 1 week after the end of treatment. The oral cavity was examined weekly, with a score given to each site based on the degree of mucositis using a 4-point scale, and a mean mucositis score was calculated as the primary outcome. Occurrence of OM, pain, QoL, and adverse effects were defined as secondary outcomes. Patients, therapists, and outcome assessors were blinded to group allocation. Results: No significant group differences occurred in the mucositis score, pain, or QoL. Mucositis occurrence rates were higher in the benzydamine hydrochloride group compared with the honey-lemon group (hazard ratio = 2.1, 95% confidence interval: 1.1 to 4.2). Two patients in the honey-lemon group had mild nausea and burning throat; no adverse effects occurred in the benzydamine hydrochloride group. Conclusions: There were no significant group differences in mucositis severity between patients treated with honey-lemon spray and benzydamine hydrochloride. The potential preventive effects of honey-lemon spray need to be confirmed in further trials. The trial registration number is IRCT20161024030467N1.

Phase I Study in Healthy Women of a Novel Antimycotic Vaginal Ovule Combining Econazole and Benzydamine.

Purpose: A novel fixed-dose combination of 150 mg of econazole with 6 mg of benzydamine formulated in vaginal ovules was investigated in a randomised, double-blind, four-parallel group, tolerability, and pharmacokinetic Phase I study in healthy women. Methods: The fixed-dose combination was compared to econazole and benzydamine single-drug formulations and with placebo after daily applications for 3 consecutive days. Safety and tolerability were evaluated recording the adverse drug reactions, local and general tolerability scores, clinical laboratory assays, and vital signs. Econazole, benzydamine, and its metabolite benzydamine N-oxide pharmacokinetics were investigated after single and multiple applications. Results: Local reactions were generally absent. Pruritus and pain at the application site were infrequently reported. According to the subjects' evaluations, the overall tolerability of the ovules was rated as excellent or good. No significant effect of any treatment on laboratory parameters, vital signs, body weight, vaginal pH, or ECG was observed. Very low econazole, benzydamine, and benzydamine-N-oxide concentrations were measured in plasma, though quantifiable in almost all samples. Conclusion: The tested fixed-dose combination showed a good safety profile consistently with the known tolerability of both active substances. In addition, the confirmed low bioavailability of the drugs excludes the possibility of any accumulation effects and limits the risk of undesired systemic effects. This trial is registered at ClinicalTrials.gov with the identifier NCT02720783 last updated on 07 February 2017.

Effectivity of benzydamine hydrochloride gargle to reduce propofol consumption in endoscopic retrograde cholangiopancreatography procedure: a randomized controlled trial.

BACKGROUND: Endoscopic Retrograde Cholangiopancreatography (ERCP) is a complex endoscopic procedure that requires moderate to deep sedation. Propofol is the sedative agent of choice for sedation in ERCP due to its fast distribution and fast elimination time without a cumulative effect after infusion, resulting in shorter recovery time. Benzydamine hydrochloride is a topical non-steroidal anti-inflammatory drug that has analgesic, local anesthetic, and anti-inflammatory effects that have been known to be effective in reducing postoperative sore throat. Combination of propofol and topical analgesic may provide adequate sedation and reduce propofol consumption. This study aimed to determine the effectivity of benzydamine hydrochloride gargling in reducing propofol consumption in the ERCP procedure. METHODS: This study was a single-blind randomized controlled trial for patients undergoing ERCP procedures at Cipto Mangunkusumo Hospital from August to September 2018. A total of 72 subjects were recruited consecutively and randomly assigned into two groups. The first group received 15 mL of 0.15% benzydamine hydrochloride mouthwash prior to the procedure, whereas the second group received 15 mL of water mouthwash. Additional propofol was administered when patient moved or Ramsay Sedation Scale rose above 4. Cumulative propofol consumption per kg body weight per minute and incidence of postoperative sore throat were recorded in each group. Incidence of desaturation, postoperative nausea vomitting, and dysphagia were also recorded. Data analysis was performed with Statistical Package for the Social Sciences. RESULTS: Cumulative propofol consumption per minute per kg body weight in the benzydamine hydrochloride group was 152.7 (91.9-238.8) mcg/kg/minute, while in the control group was 200.05 (114.4-380.2) mcg/kg/ minute (p = < 0.001). The incidence of sore throat on the 0th, 2nd, and 4th hour for the benzydamine hydrochloride group was 11.4, 11.4, and 5.7%, while in the control group was 50, 52.8, and 36.1% (p = < 0.001, < 0.001, 0.003). Desaturation was found in control group whereas none in benzydamine hydrochloride group. Complaints of nausea and vomiting were comparable in both groups. CONCLUSION: Benzydamine hydrochloride gargling was effective in reducing cumulative propofol consumption in the ERCP procedure. TRIAL REGISTRATION: Study was registered retrospectively in ClinicalTrials.gov with NCT04167592 on November 8th 2019.

Effects of benzydamine hydrochloride on postoperative sore throat after extubation in children: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common, undesirable result of endotracheal intubation during general anaesthesia. This study aimed to evaluate the effectiveness of benzydamine hydrochloride (BH) spray in reducing the incidence of POST in paediatric patients. METHODS: This randomized, double-blind, prospective study included 142 children 6-12 years of age, who were randomly assigned to receive either BH spray or control. After induction of anaesthesia, direct laryngoscope was placed and BH spray was applied to the upper trachea and vocal cord in the BH group and intubation was performed using a cuffed tube lubricated with normal saline. Intubation in the control group was performed using a cuffed tube lubricated with normal saline without any intervention. The balloon was inflated to a pressure of 20 cmH2O. Patients were extubated after fully awakened and transferred to the post-anaesthetic care unit (PACU), where they were examined for the presence of POST and any adverse events 30 min after arrival to the PACU. Postoperative pain was evaluated using a smartphone application. RESULTS: Seventy-one patients were allocated to each group. The incidence of POST in the BH group did not differ from that in the control group (control: BH = 35 (49.3%): 42 (59.2%); P = 0.238); postoperative pain was also similar between the groups. Other complications, such as breath holding, secretions, coughing, laryngospasm and desaturation events, did not differ between the groups. CONCLUSIONS: Application of prophylactic BH spray to the vocal cords and upper trachea was not proven to reduce POST in paediatric patients. TRIAL REGISTRY: NCT03074968 (ClinicalTrials.gov, Feb 26, 2017).

The effects of topical chlorhexidine-benzydamine spray on laryngeal mask airway application.

BACKGROUND: Laryngeal mask airway (LMA) use is very common during anesthesia practice. Sore throat, earache, hoarseness and swallowing difficulties may occur on LMA insertion. The primary aim of this study was to describe the effects of topical application of a spray formula of chlorhexidine gluconate and benzydamine hydrochloride (Kloroben® oral spray, 30 mL) on postoperative sore throat due to LMA use. The secondary aims were to evaluate earache, swallowing difficulty, nausea and vomiting and the hemodynamic responses due to LMA insertion and the incidence of coughing, tooth clenching, desaturation and laryngeal spasms during LMA removal. METHODS: After obtaining Institutional Ethics Committee approval and written informed consent (Ref no 29/15), a total of 100 adult patients were included. In Group C, four puffs of a spray formula of chlorhexidine gluconate and benzydamine hydrochloride were applied to the nasopharyngeal area 15 min before surgery. In Group S, 0.9% saline was applied, using the same protocol. RESULTS: When both groups were compared, more patients in Group S had cough, sore throat and swallowing difficulties one hour after surgery (P<0.05), but there was no statistically significant difference at 6, 12, and 24 h between the two groups (P>0.05). The incidence of nausea, vomiting, and earaches was similar in both groups at all measurement times (P>0.05). CONCLUSIONS: Preemptive topical benzydamine hydrochloride and chlorhexidine gluconate in a spray formula may decrease the incidence of sore throat, cough and swallowing difficulties associated with LMA use.

Effect of chlorhexidine/benzydamine soaked pharyngeal packing on throat pain and postoperative nausea & vomiting in orthognathic surgery.

Pharyngeal packing is believed to reduce postoperative nausea and vomiting (PONV) frequency, but has the disadvantage of causing throat pain. The present study aimed to investigate whether applying pharyngeal packs soaked with a combination of chlorhexidine gluconate 0.2% and benzydamine hydrochloride 0.15% (CGBH) were effective in preventing postoperative throat pain and PONV in patients undergoing orthognathic surgery. A total of 101 patients scheduled for orthognathic surgery were enrolled in this prospective, double-blind, randomized study. Patients were randomly allocated into two groups: those with CGBH-soaked packing, and those with saline-soaked pharyngeal packing. PONV was recorded using a 5-point Likert scale (0: no PONV to 4: severe PONV) immediately after the surgery at 5, 10, and 30 min, and at 2, 4, 6, 12, and 24 h postoperatively. The severity of throat pain was assessed via two methods: visual analogue scale (VAS, 0: no pain, 10: severe pain) and 6-point Likert scale (0: no pain, 5: strongly severe pain) score at 2, 4, 6, 12, and 24 h postoperatively. Mean VAS scores of throat pain were significantly lower in patients receiving CGBH-soaked pharyngeal packs compared to patients receiving saline-soaked pharyngeal packs, at all measured time points. There was a tendency towards less PONV in patients receiving a CGBH-soaked pharyngeal pack compared to those receiving a saline-soaked pharyngeal pack; however, this difference did not reach statistical significance. The results of this study suggest that the usage of CGBH-soaked pharyngeal packs reduce postoperative throat pain in patients undergoing orthognathic surgery. Our results support the implementation of CGBH-soaked pharyngeal packing in orthognathic surgery practice, as a measure to improve patient comfort.

Comparative Study of the Efficacy of the Lysozyme, Benzydamine and Chlorhexidine Oral Spray in the Treatment of Acute Tonsillopharyngitis - Results of a Pilot Study.

OBJECTIVE: Lysozyme is a natural antimicrobial and immunomodulatory enzyme, which is produced as a host response to infectious agents. The objective of this study was to compare the efficacy and safety of lysozyme-based versus benzydamine and chlorhexidinebased oral spray in patients with an acute tonsillopharyngitis associated with a common cold. PATIENTS AND METHODS: A prospective twoarm pilot study (lysozyme/cetylpyridinium/lidocaine spray versus: benzydamine spray-arm 1; chlorhexidine/lidocaine spray-arm 2) was conducted in the primary health care unit. Efficacy was evaluated by the patient's self-assessment of pain, difficulty in swallowing and the throat swelling, by using the visual analog scale (VAS) at baseline and three follow-up visits. Safety was evaluated by the assessment of the frequency and severity of adverse effects. RESULTS: Lysozyme-based spray reduced pain faster than benzydamine-based spray and slower than chlorhexidine-based spray. Lysozyme-based and chlorhexidinebased sprays similarly reduced difficulty in swallowing, but were faster than benzydamine-based spray. Similar effects on the reduction of throat swelling were seen in all treated groups. All tested products showed proper safety and were well tolerated, with no serious adverse events reported. CONCLUSIONS: The lysozyme-based oral spray was shown to be effective and safe in the reduction of pain, difficulty in swallowing and throat swelling in patients with acute tonsillopharyngitis associated with a common cold. Lysozyme-based oral spray (containing natural compound with advantages of influencing immune system and preventing recurrences) had similar activity to benzydamine and chlorhexidine-based oral antiseptic sprays.

The effect of benzydamine hydrochloride on preventing postoperative sore throat after total thyroidectomy: a randomized-controlled trial.

PURPOSE: We compared the effects of benzydamine hydrochloride (BH), 10% lidocaine, and normal saline spray on preventing postoperative sore throat (POST) in patients who underwent total thyroidectomy (TT). METHODS: In this prospective, randomized, parallel-group, double-blind study, the incidence of POST at six hours after tracheal extubation was compared among three groups as a primary outcome. American Society of Anesthesiologists physical status I-II patients undergoing elective TT under general anesthesia were enrolled. Patients were randomly stratified into group C (n = 33, normal saline), group L (n = 33, 10% lidocaine), or group B (n = 33, 0.3% BH). The participants, caregiver, and investigator were blinded to group assignment. Each study drug was sprayed three times on the endotracheal tube (ETT) cuff ten seconds before intubation. Incidence and severity of POST were recorded within 24 hr postoperatively (during postanesthesia care unit stay, and at six, 12, and 24 hr after extubation). P values were adjusted for multiple comparisons. RESULTS: Ninety-nine patients were enrolled. Eighty-seven patients completed the study. The incidence of POST at six hours after tracheal extubation was similar among the three groups (group C: 31 [93.9%], group L: 29 [87.9%], and group B: 27 [81.8%]; P = 0.38). Nevertheless, the incidence of POST was significantly different among the three groups at 12 and 24 hr after TT (12 hr: P = 0.002, 24 hr: P = 0.01). The severity of POST after tracheal extubation was statistically different among the study groups (6 hr: P = 0.04, 12 hr: P = 0.01). No adverse effects were observed. CONCLUSION: Application of BH spray on the ETT cuff reduced the incidence and severity of POST at 12 hr after TT. We suggest this method to be a non-invasive and effective management option for POST without serious side effects. TRIAL REGISTRATION: Clinical Research Information Service (KCT0002627); registered 24 November, 2017.

RéSUMé: OBJECTIF: Nous avons comparé les effets de la vaporisation de chlorhydrate de benzydamine (CB), de lidocaïne 10 %, ou de solution saline sur la prévention des maux de gorge postopératoires chez les patients subissant une thyroïdectomie totale (TT). MéTHODE: Dans cette étude prospective, randomisée, en parallèle et à double insu, l'incidence des maux de gorge postopératoires six heures après l'extubation trachéale a été comparée dans trois groupes pour répondre à notre critère d'évaluation principal. Des patients de statut physique I-II selon l'American Society of Anesthesiologists et subissant une TT non urgente sous anesthésie générale ont été recrutés. Les patients ont été aléatoirement alloués au groupe C (n = 33, solution saline), au groupe L (n = 33, lidocaïne 10 %), ou au groupe B (n = 33, CB 0,3 %). Les participants, anesthésistes et chercheurs ne connaissaient pas l'allocation de groupe. Chaque médicament étudié était vaporisé trois fois sur le ballonnet du tube endotrachéal (TET) dix secondes avant l'intubation. L'incidence et la gravité des maux de gorge postopératoires ont été enregistrées dans les 24 heures postopératoires (pendant le séjour en salle de réveil, et à six, 12 et 24 h après l'extubation). Les valeurs P ont été ajustées pour tenir compte des comparaisons multiples. RéSULTATS: Quatre-vingt-dix-neuf patients ont été recrutés. Quatre-vingt-sept patients ont terminé l'étude. L'incidence des maux de gorge postopératoires à six heures après l'extubation trachéale était semblable dans les trois groupes (groupe C : 31 [93,9 %], groupe L : 29 [87,9 %], et groupe B : 27 [81,8 %]; P = 0,38). Toutefois, l'incidence de maux de gorge postopératoires était significativement différente entre les trois groupes à 12 et 24 h après la TT (12 h : P = 0,002, 24 h : P = 0,01). La gravité des maux de gorge postopératoires après l'extubation trachéale était différente d'un point de vue statistique entre les groupes à l'étude (6 h : P = 0,04, 12 h : P = 0,01). Aucun effet secondaire indésirable n'a été observé. CONCLUSION: Le recours à une vaporisation de chlorhydrate de benzydamine sur le ballonnet du tube endotrachéal a réduit l'incidence et la gravité des maux de gorge postopératoires à 12 h après une thyroïdectomie totale. Selon nos résultats, cette méthode constitue une option de prise en charge non invasive et efficace des maux de gorge postopératoires sans effets secondaires importants. ENREGISTREMENT DE L'éTUDE: Clinical Research Information Service (KCT0002627); enregistrée le 24 novembre 2017.

Tantum verde mouthwash for tonsillectomy: A prospective, double-blind, randomized control trial.

OBJECTIVES: Post-tonsillectomy pain control is still considered a challenge. Topical agents would seem to be an ideal, safe option. Our objective was to compare the efficacy of mouthwash preparation with anti-inflammatory, anesthetic, and analgesic properties (Tantum Verde®, 0.15% benzydamine hydrochloride) with that of placebo in improving post-tonsillectomy morbidity. METHODS: A prospective, double blind, randomized clinical trial was performed. Patients older than 12-years-of-age who underwent tonsillectomy were recruited. Participants were randomized into 2 groups to receive either 0.15% benzydamine hydrochloride (TV) mouthwash solution (study arm) or a placebo solution. They were instructed to gargle the intervention they received 3 times a day for 7 days following surgery. Primary outcomes were intensity and duration of post-operative pain (using VAS visual analogue score) during a 2-week follow-up period. Secondary outcomes were pain medication demand, readmission, incidence of post-operative bleeding, hospital stay duration, and time to resume normal solid diet. RESULTS: Thirty-nine patients completed the study, of whom 23 received TV and 16 received placebo. The mean age was 23.1 years. There was no significant difference between the groups in the primary or secondary outcomes. CONCLUSIONS: The data suggest that topical treatment with TV mouthwash solution was not found to be superior to placebo in the management of post-tonsillectomy pain, bleeding, and return to a regular solid diet. Further research studies should be designed to investigate the ideal treatment for reducing post-tonsillectomy morbidity. CLINICAL TRIAL REGISTRATION: NIH identifier: NCT02190762; IRB NHR002814.

Oral flurbiprofen spray for postoperative sore throat and hoarseness: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Sore throat and hoarseness are common complications after surgery. Flurbiprofen spray has been successfully used for treatment of oral inflammations, but its effects on postoperative sore throat and hoarseness are unknown. We conducted this study to evaluate the effectiveness of flurbiprofen spray on postoperative sore throat and hoarseness, by comparing it with benzydamine hydrochloride spray and placebo. METHODS: One hundred fifty patients who were scheduled to undergo elective ear surgery were enrolled. Patients were randomized to three groups of 50 patients each; flurbiprofen oral spray, benzydamine hydrochloride oral spray and placebo spray groups. Patients received sprays just before intubation, and the incidence and severity of postoperative sore throat and hoarseness were evaluated by a blinded investigator at 0, 1, 6 and 24-hour post extubation. Patients were also questioned for possible side effects at all time points. RESULTS: The sore throat severity scores were significantly lower in treatment groups when compared to placebo group at all time points (P=0.003/108). Similarly, the incidence of sore throat was significantly lower in both of the treatment groups (P=0.007/104). The incidence of hoarseness and hoarseness scores were significantly lower in treatment groups when compared to placebo group (P=0.006/105 and P=0.005/104, respectively). While none of the patients complained of any adverse effects in flurbiprofen group, only two patients in benzydamine hydrochloride group experienced numbness. CONCLUSIONS: Both oral flurbiprofen and benzydamine hydrochloride sprays were found to be more effective than placebo in decreasing the incidence and severity of postoperative sore throat and hoarseness, with no adverse effects.

Topical benzydamine hydrochloride for prevention of postoperative sore throat in adults undergoing tracheal intubation for elective surgery: a systematic review and meta-analysis.

Postoperative sore throat has a negative impact on patient satisfaction and recovery. Benzydamine hydrochloride is a non-steroidal anti-inflammatory drug available for topical use. We performed a systematic review and meta-analysis to assess the efficacy and safety of topical application of benzydamine to prevent postoperative sore throat in adults undergoing elective surgery under general anaesthesia. We searched PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials to identify relevant randomised controlled trials and pooled the data using a random effects model. The primary outcomes were the incidence and severity of sore throat 24 h after surgery/extubation, and adverse events. The quality of evidence was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) criteria. Thirteen randomised controlled trials involving 1842 patients were included. Compared with control patients who did not receive analgesia, benzydamine was associated with a decreased incidence of postoperative sore throat, with a risk ratio (95%CI) of 0.31 (0.20-0.47), but not with significantly reduced severity, the standardised mean difference (95%CI) being -0.27 (-0.63 to 0.08). There were no significant adverse events related to benzydamine. Benzydamine was also associated with a reduced incidence of postoperative sore throat when compared with lidocaine, with a risk ratio (95%CI) of 0.18 (0.07-0.43). We judged the evidence for the outcome 'incidence of postoperative sore throat' as high quality.

Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action.

Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential.

Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

PURPOSE: The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. MATERIALS AND METHODS: Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. RESULTS: Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. CONCLUSIONS: Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

PURPOSE: The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. METHODS: Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. RESULTS: The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. CONCLUSIONS: For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Design, Development and In vitro/Ex vivo Evaluation of Mucoadhesive Buccal Film of Benzydamine Hydrochloride for the Effective Treatment of Aphthous Stomatitis.

BACKGROUND: During the recent two decades, the development of mucoadhesive drug delivery system has been gained tremendous importance to cure many recurrent diseases of the oral cavity. The drug delivery through the buccal route is quite challenging due to limited absorption area, movements of the target region and regular flow of saliva lead to the sub-therapeutic drug level in the buccal region. OBJECTIVE: The aim is to develop unidirectional release mucoadhesive buccal film for the mucosal delivery of Benzydamine Hydrochloride (WO2016126217Al, EP0812193B1) and evaluate the effects of a different grade of HPMC polymer (US5980942A) with the presumption to prolong the residence time and therapeutic effectiveness at the target site. METHODS: Mucoadhesive buccal films were prepared by solvent casting evaporation method by employing different grades of HPMC as mucoadhesive and rate controlling polymer. Total twenty-four formulations were developed using ethyl cellulose as a backing layer. The prepared films were subjected to various physicochemical parameters. RESULTS: The physicochemical parameters were found to be varied according to the type and concentration of polymer used. On the basis of in vitro drug release, desired ex-vivo mucoadhesive time, mucoadhesive force the formulations F4, F9, F14 and F19 were subjected to ex vivo drug permeation study. The F14 film containing 1% w/v of HPMC K50M was considered optimized final formulation due to higher ex vivo drug permeation. Drug-excipient compatibility was confirmed by FTIR and DSC. XRD of final formulation revealed the amorphous nature of drug. SEM indicated the perfect binding between backing and adhesive layer. CONCLUSION: The developed mucoadhesive buccal film having adequate physicochemical properties was capable to provide prolonged residence time and sustained delivery as compared to existing conventional therapies.

Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.

Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol® 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol® 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm2, while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm2. N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat / Estudo comparativo entre cloridrato de benzidamina em gel, lidocaína a 5% em gel e lidocaína a 10% em spray no balonete do tubo endotraqueal em relação à dor de garganta pós-operatória

ABSTRACT Postoperative sore throat is a common complication after endotracheal intubation. After tracheal intubation, the incidence of sore throat varies from 14.4% to 50%. The aim of the study was to compare between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on the endotracheal tube cuff as regards postoperative sore throat. The present study was carried out on 124 patients admitted to Alexandria university hospitals for lumbar fixation surgery requiring general anesthesia. Patients were randomly allocated into 4 groups. Benzydamine hydrochloride gel, 5% lidocaine hydrochloride gel, 10% lidocaine hydrochloride spray, or normal saline were applied on endotracheal tube cuffs before endotracheal intubation. The patients were examined for sore throat (none, mild, moderate, or severe) at 0, 1, 6, 12, and 24 h after extubation. The results were collected, analyzed and presented in table and figure. The highest incidence of postoperative sore throat occurred at 6 h after extubation in all groups. There was a significantly lower incidence of postoperative sore throat in the benzydamine group than 5% lidocaine gel, 10% lidocaine spray, and normal saline groups. The benzydamine group had significantly decreased severity of postoperative sore throat compared with the 10% lidocaine, 5% lidocaine, and normal saline groups at observation time point. Compared with the 5% lidocaine the 10% lidocaine group had significantly increased incidence and severity of postoperative sore throat after extubation. Compared with normal saline the 10% lidocaine group had increased incidence of postoperative sore throat. There were no significant differences among groups in local or systemic side effects. So in conclusion, benzydamine hydrochloride gel on the endotracheal tube cuff is a simple and effective method to reduce the incidence and severity of postoperative sore throat. Application of 10% lidocaine spray should be avoided because of worsening of postoperative sore throat where incidence increased but not the severity in relation to 5% lidocaine gel. Applying 5% lidocaine on the endotracheal tube cuff does not prevent postoperative sore throat but its application is better than lidocaine 10% spray or saline.

RESUMO A dor de garganta pós-operatória (DGPO) é uma complicação comum após a intubação traqueal. Em seguida a esse procedimento, a incidência de dor de garganta varia de 14,4 a 50%. O objetivo do estudo foi comparar os efeitos da aplicação de cloridrato de benzidamina em gel, lidocaína a 5% em gel e lidocaína a 10% em spray no balonete do tubo endotraqueal, no que diz respeito à dor de garganta pós-operatória. O presente estudo foi feito com 124 pacientes internados em hospitais universitários de Alexandria para cirurgia de fixação lombar que necessitavam de anestesia geral. Os pacientes foram aleatoriamente alocados em quatro grupos. Procedeu-se à aplicação de cloridrato de benzidamina em gel, cloridrato de lidocaína a 5% em gel, cloridrato de lidocaína a 10% em spray ou salina normal nos balonetes do TET antes da intubação endotraqueal. Os pacientes foram examinados para dor de garganta (nenhuma, leve, moderada ou intensa) a 0, uma, seis, 12 e 24 horas após a extubação. Os resultados foram coletados, analisados e apresentados em tabelas e figuras. A maior incidência de DGPO ocorreu seis horas após a extubação em todos os grupos. Houve incidência significativamente menor de DGPO no grupo de benzidamina versus grupos de lidocaína a 5% em gel, lidocaína a 10% em spray e salina normal. O grupo tratado com benzidamina exibiu redução significativa na intensidade da DGPO, em comparação com os grupos de lidocaína a 10%, lidocaína a 5% e salina normal no ponto no tempo de observação. Em comparação com lidocaína a 5%, o grupo tratado com lidocaína a 10% exibiu incidência e intensidade significativamente aumentadas na DGPO após a extubação. Em comparação com salina normal, o grupo tratado com lidocaína a 10% exibiu maior incidência de DGPO. Não foram observadas diferenças significativas entre grupos quanto a efeitos colaterais locais ou sistêmicos. Assim, em conclusão, o uso de cloridrato de benzidamina em gel no balonete do TET é um método simples e eficaz para reduzir a incidência e a gravidade da DGPO. Deve-se evitar a aplicação de lidocaína a 10% em spray, devido ao agravamento da DGPO, visto ter ocorrido aumento na incidência, mas não na severidade, em relação à lidocaína a 5% em gel. A aplicação de lidocaína a 5% no balonete do TET não impede a ocorrência da DGPO, mas a sua aplicação oferece melhores resultados do que lidocaína a 10% em spray, ou solução salina.

Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat.

Postoperative sore throat is a common complication after endotracheal intubation. After tracheal intubation, the incidence of sore throat varies from 14.4% to 50%. The aim of the study was to compare between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on the endotracheal tube cuff as regards postoperative sore throat. The present study was carried out on 124 patients admitted to Alexandria university hospitals for lumbar fixation surgery requiring general anesthesia. Patients were randomly allocated into 4 groups. Benzydamine hydrochloride gel, 5% lidocaine hydrochloride gel, 10% lidocaine hydrochloride spray, or normal saline were applied on endotracheal tube cuffs before endotracheal intubation. The patients were examined for sore throat (none, mild, moderate, or severe) at 0, 1, 6, 12, and 24h after extubation. The results were collected, analyzed and presented in table and figure. The highest incidence of postoperative sore throat occurred at 6h after extubation in all groups. There was a significantly lower incidence of postoperative sore throat in the benzydamine group than 5% lidocaine gel, 10% lidocaine spray, and normal saline groups. The benzydamine group had significantly decreased severity of postoperative sore throat compared with the 10% lidocaine, 5% lidocaine, and normal saline groups at observation time point. Compared with the 5% lidocaine the 10% lidocaine group had significantly increased incidence and severity of postoperative sore throat after extubation. Compared with normal saline the 10% lidocaine group had increased incidence of postoperative sore throat. There were no significant differences among groups in local or systemic side effects. So in conclusion, benzydamine hydrochloride gel on the endotracheal tube cuff is a simple and effective method to reduce the incidence and severity of postoperative sore throat. Application of 10% lidocaine spray should be avoided because of worsening of postoperative sore throat where incidence increased but not the severity in relation to 5% lidocaine gel. Applying 5% lidocaine on the endotracheal tube cuff does not prevent postoperative sore throat but its application is better than lidocaine 10% spray or saline.

Effect of prophylactic benzydamine hydrochloride on postoperative sore throat and hoarseness after tracheal intubation using a double-lumen endobronchial tube: a randomized controlled trial.

PURPOSE: We evaluated the prophylactic effect of benzydamine hydrochloride (BH) spray on postoperative sore throat and hoarseness secondary to intubation with a double-lumen endobronchial tube (DLT). METHODS: Ninety-two adult patients undergoing thoracic surgery using DLT intubation were studied. The DLT cuff and oropharyngeal cavity were sprayed with normal saline (Group S; n = 46) or BH (Group BH; n = 46) prior to intubation. Postoperative sore throat and hoarseness were evaluated at one, six, and 24 hr after surgery. Sore throat was evaluated using a 0-100 mm visual analogue scale (VAS). Hoarseness was defined as a change in voice quality. RESULTS: Compared with Group S, postoperative sore throat occurred less frequently in Group BH at one hour (mean difference, 28.3%; 95% confidence interval [CI], 8.7 to 45.1; P = 0.01), at six hours (mean difference, 32.6%; 95% CI, 12.6 to 49.2; P < 0.01), and at 24 hr (mean difference, 28.3%; 95% CI, 9.3 to 44.7; P = 0.01) after surgery. Group BH had lower VAS scores for postoperative sore throat at one hour (mean difference, 12.8; 95% CI, 4.9 to 20.7), at six hours (mean difference, 11.9; 95% CI, 4.8 to 19.1; P < 0.01), and at 24 hr (mean difference, 5.3; 95% CI, 0.9 to 9.7; P = 0.01) after surgery. Hoarseness also occurred less frequently in Group BH at one hour (mean difference, 23.9%; 95% CI, 6.8 to 39.6; P = 0.01), at six hours (mean difference, 23.9%; 95% CI, 7.4 to 39.3; P = 0.01), and at 24 hr (mean difference, 21.7%; 95% CI, 5.5 to 37.0; P = 0.02) after surgery (P < 0.01). CONCLUSIONS: Prophylactic application of BH to the DLT cuff and oropharyngeal cavity reduces the incidence and severity of postoperative sore throat and the incidence of hoarseness associated with DLT intubation. The trial was registered at the Clinical Research Information Service (KCT0001068).