The Effects of Three Oral Sprays onPlaque and Gingival InflammationF. Yesim Bozkurt,* Mine Ozturk,* and Zuhal Yetkin*

Background: The aim of this clinical trial was to comparethe effects of three oral sprays containing chlorhexidine(CHX), benzydamine hydrochloride (B-HCl), and CHX plusB-HCl (CHX/B-HCl) on plaque and gingivitis.

Methods: Fifty-one periodontally healthy volunteers, ran-domly divided into three spray groups, refrained from all me-chanical oral hygiene measures for 7 days and, instead, usedone of the randomly assigned sprays twice daily. The plaqueindex (PI), gingival index (GI), and gingival bleeding time in-dex (GBTI) were assessed at days 0 and 7. Side effects werealso evaluated.

Results: In all groups, PI, GI, and GBTI showed significantincreases from the baseline to day 7. There were no significantside effects for B-HCl spray and CHX spray at day 7, but, forCHX/B-HCl, burning sensation significantly increased fromthe baseline. For all parameters, there were significant differ-ences between B-HCl and CHX/B-HCl and between B-HCland CHX, but no significant differences were observed be-tween CHX/B-HCl and CHX. In addition, a significant differ-ence was found between CHX/B-HCl and CHX with regard toburning sensation.

Conclusions: These results indicate that both CHX andCHX/B-HCl sprays have equal clinical effectiveness, butonly B-HCl spray has less anti-plaque and anti-gingivitiseffects. Furthermore, CHX/B-HCl spray causes more sideeffects. J Periodontol 2005;76:1654-1660.

KEY WORDS

Benzydamine hydrochloride; chlorhexidine; stains.

The relationship between dentalplaque and the development ofhuman gingivitis is known. The

removal of newly formed plaque by oralhygiene measures results in the reversalof gingivitis.1 The chemical control ofplaque and gingivitis is an effectivemethod to complete or replace mechan-ical removal.2-5 The efficacy of chlor-hexidine (CHX) as a bacteriostatic andbactericidal agent in dental plaque con-trol has long been proved.6-8 CHX showsdifferent effects at different concentra-tions; at low concentrations, the agentis bacteriostatic, whereas at higher con-centrations the agent is rapidly bacteri-cidal.9-11

CHX binds to the different surfaceswithin the mouth (teeth and mucosa)and also to the pellicle and saliva, andits persistence or substantivity at the oralsurfaces has been shown to suppress sal-ivary bacterial counts for 12 hours.11

CHX should be aimed at individualswith compromised oral hygiene due tothe inability to perform adequate me-chanical oral hygiene measures. Thestudies on CHX as an anti-plaque agentindicated that rinsing with 10 ml 0.2%mouthwash for 1 minute twice a day fora total of 40 mg CHX, as well as 15 ml0.12% solution for a total of 36 mgCHX, is proven to be effective in plaquecontrol.11

However, several side effects limitingpatients’ acceptance of mouthrinsinghave been identified: brown staining ofteeth, an unpleasant taste, and rarelypainful desquamations of the oral mu-cosa.12-14 Alternative means of CHX de-livery systems have been developed,

* Department of Periodontology, Faculty of Dentistry, Suleyman Demirel University, Isparta,Turkey.

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aiming to facilitate CHX usage and to minimize sideeffects; these include gel14-16 and spray formula-tions.14-21 The effectiveness of a spray of CHX in pre-venting plaque accumulation and gingivitis has beeninvestigated for several years.15-22 The spray formoffers a very simple method of applying CHX and isusually well accepted by patients, and it is associatedwith fewer side effects than mouth rinsing,20 but it isnot the most clinically effective system.15,16

Benzydamine hydrochloride (B-HCl) is a non-steroidal anti-inflammatory analgesic agent that actspartly through an inhibitory effect on the phospholi-pase A2 by diminishing the liberation of arachidonicacid from phospholipids and partly as a weak inhibitorof prostaglandin endoperoxide H synthase (PGHS) 1and/or 2 by reducing the production of prostaglan-dins.23 The use of B-HCl as a topical anti-inflammatoryagent in the mouth has long been proved. It is knownthat B-HCl has a transient local anesthetic effect byproviding pain relief.24 Hirschl et al.25 and Mahonand De Gregorio26 reported that B-HCl has no anti-bacterial effect; however, Fanaki and El-Nakeeb27

claimed that 0.1% B-HCl has an anti-bacterial effect.The content of mouthrinses and oral sprays influen-

ces their clinical effectiveness. A newly developedoral spray, containing B-HCl and CHX, is claimedby the manufacturing company to have anti-plaqueand anti-inflammatory effectiveness within the oralcavity. However, the effect of B-HCl on the CHX’santi-plaque activity is still unclear.

The aim of this parallel, randomized clinical trial isto compare three commercially available oral sprayscontaining CHX, B-HCl, and CHX plus B-HCl, respec-tively, for effects on plaque regrowth, gingival inflam-mation, and bleeding and whether B-HCl in CHX sprayhas any superiority for clinical effectiveness than theother two spray formulations.

MATERIALS AND METHODS

Study DesignThe clinical trial was a double-blind, parallel study. Atotal of 51 periodontally healthy subjects (35 femalesand 16 males) aged between 15 and 44 years (meanage 20.61 – 4.34 years) participated in this study. Thestudy was performed by a single examiner who wasblinded for spray groups, and three sprays were la-beled as A, B, and C by another investigator. SprayA was a 0.15% B-HCl spray,† which was prepared inthe same package as the others, spray B wasa 0.12% CHX plus 0.15% benzydamine HCl (CHX/B-HCl) spray,‡ and spray C was a 0.2% CHX spray.§

The systemically and periodontally healthy (GI <1and probing depth [PD] £3 mm), non-smoker subjectshad a minimum 24 teeth present. They had no pros-thetic or orthodontic appliances. None of the subjectsincluded in this study took medications such as antibi-

otics, anti-inflammatory drugs, or contraceptives for atleast 3 months. The 51 subjects admitted to the Suley-man Demirel University, Faculty of Dentistry, Depart-ment of Periodontology between May and September2003 who fit these criteria volunteered and gave theirinformed consent to participate in this study. This hu-man study has been approved by The Ethical Commit-tee of Suleyman Demirel University Faculty of Dentistry.

The subjects were equally divided into three groups(17 subjects per group) to form parallel groups andrandomly assigned into three spray groups. The meanage of group B-HCl spray was 19.12 – 2.09, groupCHX/B-HCl spray was 21.94 – 5.95, and group CHXspray was 20.76 – 3.85 years. There were no signifi-cant differences between the study groups for age andgender (P >0.05). Professional oral hygiene, which in-cluded scaling and polishing with prophylactic pasteapplied with a rubber cup, was carried out at thebeginning of the study for all the subjects by one ofthe investigators. Volunteers performed mechanicaltooth cleaning using a toothbrush during the next2 days (preparatory period). Then, at baseline (day0), 51 volunteers refrained from all mechanical oralhygiene measures for the next 7 days and insteadused 12 sprays of one of the three randomly assignedformulations twicedaily.Ateachapplication, thevolun-teers directed the spray at the buccal and lingual sur-face of teeth at the following localizations: upper rightposterior, upper anterior, upper left posterior, lowerright posterior, lower anterior, and lower left posterior.The solution was left to act for about 30 seconds. Eachsingle puff of spray released 0.13 ml solution.

Data CollectionThe amount of plaque, gingival inflammation, andgingival bleeding were assessed at day 0 and day 7.Side effects, such as staining of teeth and tongue, tastealteration, desquamation of gingival epithelium, andburning sensation, were also evaluated at this interval.

Plaque accumulation was assessed according toplaque index (PI)28 criteria. Gingival inflammationwas assessed using the gingival index (GI),29 and gin-gival bleeding was assessed using the gingival bleed-ing time index (GBTI).30

The staining index (SI) was modified from theTuresky et al.31 modification of the Quigley and Heinplaque index.32 Staining areas at the tooth surfacewere evaluated similar to the disclosed plaque areas.For assessing tongue staining, stain on the dorsal an-terior two-thirds of the tongue was scored accordingto the following criteria33: 0 = no stain; 1 = 1% to25% coverage; 2 = 26% to 50% coverage; 3 = 51%to 75% coverage; and 4 = 76% to 100% coverage.

† Drogsan Laboratory, Drogsan, Istanbul, Turkey.‡ Kloroben, Drogsan.§ Klorhex, Drogsan.

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Taste alteration was evaluated using a visual ana-log scale; each patient was asked to qualify the alter-ation on the basis of his/her own personal sensationson a scale from 0 to 5. The presence of a burning sen-sation was asked of each patient and evaluated aspresent or absent. The desquamation of gingival epi-thelium was also evaluated as present or absent uponintraoral examination.

Statistical AnalysisThe differences were analyzed between the baselineand seventh day mean PI, GI, GBTI, SI, and tonguestaining values within each group and between thespray groups by using an independent samples t test.A value of P <0.05 was chosen as the level of signifi-cance. The differences between the spray groups re-garding taste alteration, desquamation, and burningsensation were compared by using the Mann-WhitneyU test. Statistical analyses were conducted using acomputer program.i

RESULTS

A total of 51 subjects, including 35 females and 16males, completed the study. The baseline and day 7mean PI, GI, GBTI, and SI scores of the study groupsare summarized in Table 1. In all groups, PI, GI, andGBTI showed significant increases from baseline to

day 7 (P = 0.000). There were no significant differ-ences between group CHX/B-HCl spray and CHXspray (P >0.05), but there were statistically significantdifferences between group B-HCl spray and CHX/B-HCl spray (P = 0.000) and between group B-HClspray and CHX spray (P = 0.000) for PI at day 7. Sim-ilar results were obtained for GI, GBTI, and SI.

Tongue staining was observed in some subjects,but clinically or statistically significant differences be-tween the groups were not found for this side effect.The number of subjects and median scores of tonguestaining index is submitted in Table 2.

There were no significant side effects for B-HClspray and CHX spray groups at day 7, but, in groupCHX/B-HCl, spray burning sensation significantly in-creased from baseline (P = 0.034). Furthermore, sta-tistically significant differences were found betweengroup CHX/B-HCl spray and group B-HCl spray andbetween group CHX/B-HCl spray and group CHXspray about burning sensation (P = 0.000). The distri-bution of side effects is shown in Table 3.

DISCUSSION

The present study aimed to compare anti-plaque andanti-gingivitis effects of three oral sprays containing

Table 1.

Evaluations of Plaque Index, Gingival Index, Gingival Bleeding Time Index, and StainIndex by Group Means at Baseline and Day 7

Variable

Spray

B-HCl

N = 17

(mean – SD)

Spray

CHX/B-HCl

N = 17

(mean – SD)

Spray

CHX

N = 17

(mean – SD)

Comparisons of Groups at Day 7

(P value)

B-HCl and

CHX/B-HCl

B-HCl and

CHX

CHX/B-HCl and

CHX

PIDay 0 0.05 – 0.09 0.04 – 0.03 0.02 – 0.03Day 7 1.09 – 0.25 0.50 – 0.39 0.38 – 0.35 0.000* 0.000* 0.35P value (days 0 to 7) 0.000* 0.000* 0.000*

GIDay 0 0.06 – 0.09 0.04 – 0.03 0.04 – 0.09Day 7 0.44 – 0.22 0.27 – 0.17 0.22 – 0.22 0.018* 0.005* 0.37P value (days 0 to 7) 0.000* 0.000* 0.005*

GBTIDay 0 0.18 – 0.24 0.15 – 0.19 0.10 – 0.12Day 7 1.01 – 0.48 0.68 – 0.42 0.50 – 0.42 0.042* 0.002* 0.22P value (days 0 to 7) 0.000* 0.000* 0.001*

SIDay 0 0.002 – 0.009 0.000 – 0.000 0.000 – 0.000Day 7 0.65 – 0.50 1.54 – 0.80 1.36 – 0.70 0.001* 0.002* 0.48P value (days 0 to 7) 0.000* 0.000* 0.000*

* Statistically significant (P <0.05) in independent samples t test.

i SPSS package program for Windows, SPSS, Chicago, IL.

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B-HCl, CHX/B-HCl, and CHX and to evaluate whetherB-HCl in CHX has an additional clinical effect com-pared to the CHX and CHX/B-HCl sprays. Moreover,side effects of a newly developed commercial oralspray containing 0.12% CHX plus 0.15% B-HCl werecompared to the side effects of 0.2% CHX spray and0.15% B-HCl spray. This study was conducted ina parallel design similar to the studies of Winkel etal.34 and Roldan et al.35 The clinical effect of CHXand B-HCl are already known. These formulationshave been used as positive control in our study. Sincethe aim of our study was to evaluate the clinical effectof the new formulation (CHX/B-HCl), a negative con-trol group has not been constituted. There are somestudies including the same approach in the litera-ture.20,36 In the present study, 7 days of oral sprayusage was considered as a sufficient period for assess-ing the effects of three oral sprays.20,36 Twelve spraysof the formulations were used twice daily.16-19,21,37

Since the action of spray is applied directly on theteeth, it has been suggested that a possible mecha-nism of CHX derives from its adsorption on the toothsurface, from where it exerts its anti-plaque effect.11

The studies revealed that CHX is the gold standardfor controlling plaque regrowth and gingivitis.38 Theexcellent clinical results achieved in the short-termclinical trials with CHX were also attained as a resultof the long-term studies.6,13,15,18

The non-steroidal anti-inflammatoryagent B-HCl is used for symptomatictreatment of edematous postoperativeor traumatic swelling and non-specific in-flammation in the oral cavity. Sironi etal.39 demonstrated that B-HCl inhibitedtumor necrosis factor-alpha (TNF-a)production in vitro by human lipopoly-saccaride-stimulated monocytes andwith mouse cells interleukin (IL)-1 pro-duction in vitro. Hirschl et al.25 comparedthe antibacterial efficacy of B-HCl, hexe-tidine, dequaliniumchloride, and hydro-gen peroxide and reported that B-HClhas no antibacterial effect. In a critical re-view, Mahon and De Gregorio26 reportedthat B-HCl has no antibacterial effect;however, Fanaki and El-Nakeeb27 evalu-ated bactericidal activity of B-HCl by theviable count technique against 12 multi-fold resistant clinical isolatesandclaimedthat 0.1% B-HCl has an antibacterialeffect. A study comparing B-HCl andplacebo has suggested that B-HCl exhib-ited anti-plaque activity.40 In that cross-over study, 25 patients were involved,no scaling and root planing were per-formed, patients rinsed with B-HCl or pla-

cebo three times a day and brushed once a day duringthetwo7-daytestperiodsseparatedbya2-weekwash-out period. The comparisons of PI scores at day 0 andday 21 indicated that the difference was significant.

Short- and long-term studies highlighted that therewere no significant differences between application of0.2% or 0.12% CHX concentrations for anti-plaqueand anti-gingivitis effectiveness.7,41,42 The applica-tions of 0.2% and 0.12% CHX spray concentrationswere used in the present study. When we analyzedthe alterations in PI in each group, CHX/B-HCl spraydid not show any difference with respect to CHX sprayfor the control of dental plaque. Protection was quiteeffective from dental plaque accumulation with0.2% CHX spray and 0.12% CHX plus 0.15% B-HClspray. The PI scores in the group CHX and the groupCHX/B-HCl were consistently lower than the groupB-HCl. The mean PI scores of CHX spray and CHX/B-HCl spray were compatible with the results of Clav-ero et al.21 and Francetti et al.20 But Kalaga et al.17

performed a 4-day plaque regrowth study in healthysubjects and reported that the mean PI score of CHXspray group was 0.0407 at the end of the study. Inthe present study, after CHX spray and CHX/B-HClspray applications, the PI scores were higher thanthose scores. Keijser et al.42 evaluated two commer-cially available mouthrinses containing 0.2% and0.12% CHX for inhibition of plaque accumulation over

Table 2.

Number and Median Scores of Subjects With TongueStaining

Spray

Formulation

N

(total = 51)

Subjects

With Tongue Staining

Tongue Staining Index

Median Score*

B-HCl 17 6 1 (0% to 25%)

CHX/B-HCl 17 10 1 (0% to 25%)

CHX 17 9 2 (26% to 50%)

* Scores of tongue staining index33 were explained in Materials and Methods.

Table 3.

Side Effects of Groups at Day 7

Side Effects

B-HCl

(n)

CHX/B-HCl

(n)

CHX

(n) P Value

Taste alteration 1/17 4/17 2/17 0.24

Desquamation 1/17 2/17 2/17 0.43

Burning sensation 0/17 5/17 0/17 0.034*

* Statistically significant (P <0.05), Mann-Whitney U test.

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a period of 72 hours, and they reported that the meanPI score of the 0.12% CHX group was 1.65 and themean PI score of the 0.2% CHX group was 1.60. Therewere no statistically significant differences among thegroups. When a comparison was made between theresults of the Keijser et al.42 study and the presentstudy, it was shown that the PI scores of present studygroups containing CHX were consistently lower thanthe PI scores of that study. For the short-term applica-tion, oral sprays may be more efficient than mouth-rinses for plaque prevention.

In the absence of oral hygiene, gingivitis couldbe resolved by rinsing with CHX mouth rinse.14

Grossman et al.43 demonstrated that rinsing with0.12% CHX mouth rinse during a 6-month periodachieved reductions in GI scores of 30% to 45% andreductions in gingival bleeding of 25% to 52%. Claveroet al.21 reported that one or two daily applications of0.2% CHX spray decreased GI scores approximately50% in an older adult population. In a study performedon adults with disabilities, it was shown that 0.2% CHXspray application resulted in a reduction of 43.58%,38.75%, and 59.39% of bleeding sites in buccal, me-sial, and lingual areas, respectively.18 However,Franciset al.15 reported a slight decrease by 0.2% CHX sprayapplication in children with disabilities. In the presentstudy, seventh day GI scores of the group CHX spraywere similar to those of the group CHX/B-HCl spray. Inreducing gingival bleeding, CHX/B-HCl spray wasless effective than CHX spray. The anti-inflammatoryeffect of B-HCl did not contribute to the anti-gingivitiseffect of CHX.

Francis et al.15 claimed that there was no clinicallyor statistically significant difference between 0.2%CHX mouthwash, 0.2% CHX spray, and 1% CHX gelapplication with respect to tooth staining in childrenwith disabilities. In a similar way, Francetti et al.20

showed 0.2% CHX spray and 0.12% CHX mouthwashapplication of surgically involved sites had similar ef-fects on tooth staining. In these studies, staining wasevaluated for intensity only, but, in the present study,staining was assessed both in terms of intensity andlocalization. For this purpose, the Turesky et al.31

modification of Quigley and Hein plaque index32

criteria were used for stain area. There was morestaining in terms of intensity and localization in theCHX-containing spray groups.

Claydon et al.33 have evaluated the effect of poly-vinyl pyrrolidone on the activity of CHX mouthwash.They have found no differences between the groupsregarding tongue staining and stated that the mainfeature in staining is the high intake of dietary chrom-ogens rather than the presence of cationic agents. Inthe present study, there were no significant differ-ences between the spray groups although they con-tain the cationic agent CHX.

The CHX usage results in burning sensation, des-quamation of oral mucosa, taste alterations, and dis-coloration of the tongue and teeth.12-14 Burningsensation is one of the most reported side effects.12,44

In the present study, burning sensation with CHX/B-HCl spray was significantly greater than that ofthe CHX spray. The addition of B-HCl may havecaused this situation. B-HCl was reported to havesome side effects, including numbness of the tissuesin the oral cavity and sensation of tingling in the tis-sues of the oral cavity.45

The limitation of this study was the commerciallydifferent CHX concentrations in the sprays. The smallsizes of the study groups may seem to be a limitationin interpreting the reported results in the presentstudy. However, the sample size was found sufficientfor this parallel study when the power calculationswere made in the beginning of the study.

Consequently, based on the results of this study,the addition of B-HCl in CHX spray did not provide su-periority for plaque elimination and the prevention ofgingival inflammation.

CONCLUSION

The present results indicate that CHX and CHX/B-HClsprays have equal clinical effectiveness, but the anti-plaque and anti-gingivitis effects of the B-HCl spraywere not as effective as both of the CHX-containingsprays.

ACKNOWLEDGMENTS

The authors are indebted to Dr. Ibrahim Gungor (Su-leyman Demirel University, Faculty of Economics andAdministrative Sciences, Isparta, Turkey) and Dr.Hikmet Orhan (Suleyman Demirel University, Facultyof Agriculture, Isparta, Turkey) for their help in con-ducting statistical analyses.

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44. Groppo FC, Ramacciato JC, Simoes RP, Florio FM,Sartorato A. Antimicrobial activity of garlic, tea treeoil, and chlorhexidine against oral microorganisms. IntDent J 2002;52:433-437.

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Correspondence: Dr. Mine Ozturk, Department of Peri-odontology, Faculty of Dentistry, Suleyman DemirelUniversity, 32260 Cunur/Isparta, Turkey. Fax: 90-0-246-227-06-07; e-mail: mine@dishek.sdu.edu.tr.

Accepted for publication February 14, 2005.

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