Research Article Development of a Sustained Antiplaque and Antimicrobial Chewing Gum of a Decapeptide Abeer M. Al-Ghananeem, 1,5 Kai P. Leung, 2 Jabar Faraj, 3 and Patrick P. DeLuca 4 Received 28 September 2016; accepted 26 December 2016 Abstract. The objective of this paper was to design a chewing gum formulation delivery system in situations where typical dental hygiene practice is not practical. Thus, an analog of decapeptide KSL (KSL-W), known to possess antimicrobial and antiplaque activity, was incorporated into a chewing gum formulation containing cetylpyridinium chloride (CPC). The effect of the excipients, xylitol, and peppermint oil on active ingredients in vitro release was also assessed. Gum formulations were prepared with different excipient parameters, including heating xylitol and gum base at 65 or 85°C, using ground and unground xylitol, and the addition of 1.5, 3, and 7% peppermint oil, to determine the effect of these changes on the in vitro release of KSL-W and CPC using a chewing machine. The antimicrobial and antiplaque activities of solutions released from chewed gum formulation as well as prepared standard solutions with different concentrations were tested against placebo. The optimal temperature to avoid crystallization of xylitol during preparation was 65°C. Grinding xylitol to 104.5 μm improved release of active ingredients as compared to commercially unground xylitol. Peppermint oil had opposite effects on release of KSL-W and CPC. Peppermint oil at 1.5% was determined to be suitable (91 and 88% of KSL-W and CPC released, respectively, after 40 min). The gum formulation illustrated good sustained release of KSL-W and CPC with antibacterial and antiplaque activities after chewing. An effective antimicrobial and antiplaque chewing gum formulation was developed. This formulation has the potential to overcome oral hygiene issues in those unable to follow normal dental protocols. KEY WORDS: antimicrobial; antiplaque; chewing gum; flavoring agent; sustained release. INTRODUCTION Bacteria in the human oral cavity can lead to diseases such as dental caries (tooth decay) and periodontal diseases such as gingivitis and periodontitis. These diseases typically begin when improper dental hygiene allows oral microbes to adhere to the salivary pellicle and develop into dental plaque (1). Further- more, excess oral bacteria can contribute to systemic diseases and have been connected to cardiovascular issues (2). Common at-home methods of dental care, such as tooth- paste and mouthwashes, help reduce plaque accumulation, but are only in the mouth for a short period of time. Alternatively, medicated chewing gums provide a means of mechanical plaque removal with incorporated antimicrobial treatments for a longer period of time. Chewing gums would be highly beneficial in conjunction with typical dental hygiene or in situations requiring alternative means of maintaining dental hygiene when brushing is not a viable option. Because of the benefits, chewing gums have been investigated for their potential in preventing plaque and reducing oral bacteria (3,4). There has been increased interest in alternative antimi- crobials, in particular naturally occurring antimicrobial pep- tides (5). These peptides tend to be prokaryote specific and do not cause microbial resistance over time. One such broad spectrum peptide is KSL-W. KSL-W is an analog of the decapeptide KSL (KKVVFKVKFK-NH 2 ) that has the lysine at the #6 position replaced with tryptophan. The potential of using various forms of KSL as an antimicrobial in chewing gums has been investigated (6–8). In particular, the variant KSL-W was found to be stable in human saliva, but rapidly degraded in gastric juices, making it an ideal candidate for a chewing gum (6). Cetyl pyridinium chloride (CPC) is a commercially available cationic quaternary ammonium salt that is 1 College of Pharmacy, Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, 22110, Jordan. 2 Dental and Craniofacial Trauma Research and Tissue Regeneration Directorate, Institute of Surgical Research, 3650 Chambers Pass, Bldg 3611, JBSA Fort Sam, Houston, Texas 78234, USA. 3 Evonik Industries, 750 Lakeshore Parkway, Birmingham, Alabama 35211, USA. 4 College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA. 5 To whom correspondence should be addressed. (e-mail: amalghananeem@just.edu.jo) AAPS PharmSciTech ( # 2017) DOI: 10.1208/s12249-016-0706-9 1530-9932/17/0000-0001/0 # 2017 American Association of Pharmaceutical Scientists