Evaluation of locally delivered biodegradable cefixime strips as an adjunct to scaling and root planing in chronic periodontitis: A clinical study

Abstract

Background and Objectives:

Local drug delivery systems provide targeted therapy within periodontal pockets, enhancing the effectiveness of nonsurgical periodontal treatment. The present study aimed to evaluate the clinical efficacy of locally delivered biodegradable cefixime strips as an adjunct to scaling and root planing (SRP) in the management of generalized chronic periodontitis.

Materials and Methods:

A split-mouth, randomized, placebo-controlled clinical trial was conducted in 40 patients diagnosed with generalized chronic periodontitis. In Group I (test group, 40 sites), biodegradable cefixime strips were inserted into sites with probing pocket depths (PPDs) ≥5 mm following SRP at baseline. In Group II (control group, 40 sites), placebo strips were inserted into sites with similar pocket depths post-SRP. Clinical parameters, including plaque index, gingival index (GI), PPD, and clinical attachment level (CAL), were recorded at baseline, 1 month, and 3 months posttreatment.

Results:

Both groups demonstrated improvement in all clinical parameters over time. However, the test group (SRP + cefixime strip) showed significantly greater reductions in PPD and GI scores and a higher gain in CAL, compared to the control group (SRP + placebo strip) at 1 and 3 months.

Conclusion:

Local delivery of biodegradable cefixime strips as an adjunct to SRP is an effective and safe therapeutic approach for the management of generalized chronic periodontitis. This technique enhances local drug concentration within periodontal pockets and exhibits bactericidal activity against major periodontal pathogens.

INTRODUCTION

Chronic periodontitis (CP) is the most prevalent form of periodontal disease and is characterized by a slow, progressive inflammatory process. It is defined as “an infectious disease resulting in inflammation within the supporting tissues of the teeth, progressive attachment loss, and alveolar bone destruction.”[1] Bacteria play a major etiological role in the initiation and progression of periodontal pockets.[2,3] Therefore, achieving periodontal healing requires the effective elimination or suppression of periodontopathogenic microorganisms within the subgingival microbiota.

Various therapeutic strategies have been proposed for the management of chronic periodontitis, including mechanical debridement through scaling and root planing (SRP), self-performed plaque control, and the use of antimicrobial agents administered either systemically or locally.[4] Adjunctive pharmacological therapies such as topical antiseptics, systemic antibiotics, and sustained-release local drug delivery (LDD) systems – such as fibers, gels, films, and strips – have been developed to enhance clinical outcomes. These localized delivery vehicles allow the controlled release of antimicrobial agents directly into periodontal pockets, thereby maintaining a high drug concentration at the target site with minimal systemic exposure. This approach has been reported to produce superior results compared to conventional systemic therapies.[5,6,7]

Previous clinical studies have examined the adjunctive benefits of various antimicrobials, including tetracycline, metronidazole, and chlorhexidine, in the management of chronic periodontitis.[8] Cefixime, a third-generation cephalosporin with a broad antibacterial spectrum, has demonstrated promising in vitro release and antimicrobial properties when incorporated into biodegradable strips.[9,10] To the best of our knowledge, the present study is the first clinical trial to evaluate the efficacy of locally delivered biodegradable cefixime strips as an adjunct to SRP in the treatment of generalized chronic periodontitis.

MATERIALS AND METHODS

This randomized, placebo-controlled, split-mouth clinical trial was conducted in the outpatient department of periodontics. Forty participants aged 20–50 years, diagnosed with generalized chronic periodontitis (CP) and presenting with bilateral pocket depths ≥5 mm and clinical attachment loss (CAL) ≥3 mm in maxillary or mandibular posterior sextants, were included. The study protocol was approved by the institutional ethical committee, and written informed consent was obtained from all participants before enrolment. Detailed medical and dental histories were recorded. Participants with a known allergy to cephalosporins, those who had received periodontal therapy within the previous 6 months, individuals with a history of drug abuse, and pregnant or lactating women were excluded from the study.

All subjects underwent SRP at baseline. Clinical parameters were recorded using a standardized pro forma. The plaque index (PI) (Silness and Löe, 1964)[11] and the gingival index (GI) (Löe and Silness, 1963)[11] were used to assess oral hygiene and gingival inflammation. Probing pocket depth (PPD) and clinical attachment level (CAL) were measured at selected sites using a customized acrylic stent and a Williams graduated periodontal probe.[12] Bilateral pocket sites were randomly assigned to test and control groups using the cointoss method.

Group I (Test: 40 sites): Following SRP, biodegradable cefixime strips were inserted into selected sites (pocket depth ≥5 mm) [Figure 1].

Figure 1.

Sequential clinical images of Group I (SRP + Cefixime strip) showing (a) baseline, (b) 1 month, and (c) 3 months post treatment

Group II (Control: 40 sites): Following SRP, placebo strips were inserted into selected sites of similar pocket depth [Figure 2].

Figure 2.

Sequential clinical images of Group II (SRP + Placebo strip) showing (a) baseline, (b) 1 month, and (c) 3 months post treatment

All clinical parameters were recorded at baseline, 1 month, and 3 months postoperatively.

Preparation of cefixime strips

Cefixime strips were prepared under aseptic conditions following the formulation described by Parmar et al.[13] The formulation (% w/w) was developed at Parul Institute of Pharmacy and Research, Parul University, Vadodara, Gujarat, India. Strips were produced by the solventcasting method using a methanol–dichloromethane mixture (1:1, v/v) as the solvent. The composition was as follows:

• Ethyl cellulose (EC) 1.8% – polymer and sustainedrelease film former

• Hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) 1.2% – copolymers/excipients for sustained release

• Dibutyl phthalate (DBP) 50% (v/w) – plasticizer

• Cefixime 0.4% (40 mg/ml) – active antimicrobial agent.

The polymers were dissolved in the solvent mixture, followed by the addition of cefixime and dibutyl phthalate with continuous magnetic stirring. The resulting solution (10 ml) was poured into a clean, levelled glass Petri dish and left to dry at 30°C for at least 24 h for complete solvent evaporation. The dried films were cut into uniform strips (0.5 × 0.4 cm²), wrapped in aluminium foil, and stored at room temperature in a dark, dry environment until use. Solvent residues were analyzed by gas chromatography to ensure safety.

In vitro drug release study

Cefixime release from the strips was evaluated using glass vials containing 1 ml of isotonic phosphate buffer (pH 6.8) as the dissolution medium, maintained at 37°C. At 24 h intervals, 1 ml aliquots were withdrawn for analysis and replaced with fresh buffer to maintain sink conditions. Cefixime release was quantified spectrophotometrically at 288.8 nm after appropriate dilution. An initial burst release was observed within 24 h due to surface elution, followed by a slow, sustained drug release for up to 5 days.

Placebo strips were prepared using pure medicinalgrade glycerin gel (Glycerin IP) without the active drug component.

RESULTS

Data were analyzed using IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics (mean ± standard deviation) were calculated for all clinical parameters at baseline, 1 month, and 3 months. Intragroup comparisons at different time intervals were performed using the paired t-test, while intergroup comparisons between the test and control sites were analyzed using the independent t-test.

Both treatment groups – Group I (SRP + cefixime strip) and Group II (SRP + placebo strip) – showed improvement in all recorded clinical parameters (PI, GI, PPD, and CAL) over the study period. However, the mean reduction in PI, GI, and PPD, as well as the gain in CAL, were significantly greater in Group I compared to Group II at both the 1month and 3month evaluations (P < 0.05).

As presented in Tables 1-4, Group I demonstrated superior clinical outcomes across all measured parameters at each time point, indicating that locally delivered cefixime strips provided an added clinical benefit when used adjunctively with SRP.

Table 1.

Comparison of plaque index scores between Group I (scaling and root planing + cefixime strip) and Group II (scaling and root planing + placebo strip) at baseline, 1 month, and 3 months

Groups	Baseline, mean±SD	1 month, mean±SD	3 months, mean±SD
Group I (SRP + cefixime strip)	1.50±0.50	1.18±0.38	1.15±0.36
Group II (SRP + placebo strip)	1.63±0.49	1.45±0.50	1.40±0.49
P #	0.26**	0.001*	0.12 (NS)

*Significant; **NS; ^#Independent t-test; P≤0.05 considered statistically significant. NS – Nonsignificant; SD – Standard deviation; SRP – Scaling and root planning; P – Probability value

Table 4.

Comparison of clinical attachment level between Group I (scaling and root planing + cefixime strip) and Group II (scaling and root planing + placebo strip) at baseline and 3 months

Groups	Baseline, mean±SD (mm)	3 months, mean±SD (mm)
Group I (SRP + cefixime strip)	7.93±0.82	7.05±0.81
Group II (SRP + placebo strip)	7.70±0.88	7.08±0.88
P #	0.24 (NS)	0.89 (NS)

^#Independent t-test; P≤0.05 considered statistically significant. NS – Nonsignificant; SD – Standard deviation; SRP – Scaling and root planing

Table 2.

Comparison of gingival index scores between Group I (scaling and root planing + cefixime strip) and Group II (scaling and root planing + placebo strip) at baseline, 1 month, and 3 months

Groups	Baseline, mean±SD	1 month, mean±SD	3 months, mean±SD
Group I (SRP + cefixime strip)	1.63±0.49	1.28±0.45	0.83±0.38
Group II (SRP + placebo strip)	1.50±0.50	1.33±0.47	1.40±0.49
P #	0.26**	0.63**	0.001*

*Significant; **NS; ^#Independent t-test; P≤0.05 considered statistically significant. NS – Nonsignificant; SD – Standard deviation; SRP – Scaling and root planning; P – Probability value

Table 3.

Comparison of probing pocket depth between Group I (scaling and root planing + cefixime strip) and Group II (scaling and root planing + placebo strip) at baseline and 3 months

Groups	Baseline, mean±SD (mm)	3 months, mean±SD (mm)
Group I (SRP + cefixime strip)	6.05±0.55	3.55±0.55
Group II (SRP + placebo strip)	5.95±0.55	4.85±0.58
P #	0.42**	0.001*

*Significant; **NS; ^#Independent t-test; P≤0.05 considered statistically significant. NS – Nonsignificant; SD – Standard deviation; SRP – Scaling and root planning; P – Probability value

DISCUSSION

Periodontitis is a chronic inflammatory disease of the periodontium initiated by bacterial infection and modulated by the host immune response. When unchecked, the disease leads to progressive tissue destruction and loss of toothsupporting structures.[14,15] Conventional nonsurgical periodontal therapy, including SRP and ultrasonic debridement, is generally effective in controlling infection and reducing inflammation.[16,17] However, to enhance therapeutic outcomes, several LDD systems with controlled- or sustainedrelease properties have been developed as adjuncts to mechanical debridement.[18]

The present study evaluated the efficacy of locally delivered biodegradable cefixime strips (Group I) as an adjunct to SRP, compared with SRP combined with placebo strips (Group II), in the management of generalized chronic periodontitis. LDD systems provide approximately 100-fold higher subgingival concentrations of antimicrobial agents compared to systemic administration.[18] This targeted approach allows the drug to reach the base of deep periodontal pockets, ensures sustained release over time, reduces bacterial load, and aids in minimizing bleeding and inflammation, ultimately contributing to better disease control.[19,20,21]

Among various LDD systems, strips are particularly advantageous owing to the ease of placement within periodontal pockets and their ability to deliver the drug site specifically. The use of biodegradable polymers also improves patient compliance, as the strips do not require removal following therapy.[22] In the present study, placebo strips were prepared using pure medicinal-grade glycerin (Glycerin IP), which has no therapeutic action; therefore, any improvement in Group II was attributable solely to SRP.

Significant improvements in all clinical parameters (PI, GI, PPD, and CAL) were observed in both groups over the 3-month study period, with greater reductions in Group I (SRP + Cefixime strip). These findings are in accordance with earlier studies conducted by Sharma and Prasad,[23] Bodduru et al.,[24] and Friesen et al.,[25] which demonstrated enhanced periodontal outcomes when antimicrobial fibers or strips were used in conjunction with SRP.

PI values reduced significantly in both groups, with Group I showing greater and sustained plaque control from baseline to 3 months. This aligns with the observations of Addy and Langeroudi,[8] who demonstrated that acrylic delivery systems containing chlorhexidine, metronidazole, or tetracycline effectively reduced subgingival microbiota when used adjunctively.

When evaluating the GI, both treatment modalities improved gingival health; however, the reduction was more pronounced and sustained in Group I, confirming the additional benefit of cefixime strips in controlling inflammation. Similar findings were reported by Dukić et al.[26]

Both groups demonstrated significant reductions in PPD, although the improvement was substantially greater in the cefixime group after 3 months. The observed results may be attributed to the bactericidal action of cefixime against subgingival pathogens and improved tissue healing following SRP, consistent with the findings of Awen B Z et al. and Friesen et al.[10,25]

CAL gains were evident in both groups during the 3-month follow-up; however, the difference between groups was not statistically significant. Similar trends were noted in the study by Addy and Langeroudi, which reported modest attachment gains following adjunctive antimicrobial strip therapy.[8]

Overall, the findings of this clinical trial suggest that the local application of biodegradable cefixime strips as an adjunct to SRP offers additional clinical benefits in reducing plaque accumulation, gingival inflammation, and probing depth in patients with generalized chronic periodontitis.

CONCLUSION

To the best of our knowledge, this is the first clinical study to evaluate the efficacy of locally delivered biodegradable cefixime strips as an adjunct to SRP in the treatment of generalized chronic periodontitis. The results demonstrated improvement in all clinical parameters at various time intervals in both groups; however, the adjunctive use of cefixime strips (Group I) yielded greater reductions in plaque accumulation, gingival inflammation, and PPD compared with SRP + placebo strips (Group II).

Within the limitations of this study, it may be concluded that the local delivery of cefixime strips in combination with SRP is an effective and patient-friendly therapeutic approach for improving periodontal health. This technique achieves higher localized drug concentrations with bactericidal activity against major periodontal pathogens, while minimizing systemic effects. The method is novel, safe, simple to use, and welltolerated. Further multicentric clinical trials, complemented by microbiological analyses, are recommended to substantiate and expand upon these findings.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.