Research Article Mechanical Characterization and Dissolution of Chewing Gum Tablets (CGTs) Containing Co-compressed Health in Gum® and Curcumin/Cyclodextrin Inclusion Complex Turki Al Hagbani, 1,2 Christopher Altomare, 3 Mohammad M. Kamal, 1 and Sami Nazzal 1,4,5 Received 11 June 2018; accepted 31 August 2018 Abstract. Curcumin chewing gums could be therapeutically beneficial if used by the head and neck cancer patients. High curcumin loading in chewing gums however is needed to achieve desired therapeutic effect. Preparing gums with high drug load is nonetheless challenging because of the negative impact of solids on their masticatory properties. The use of liquid flavors was found to partially solve this problem. The objectives of this study were to (1) determine the maximum amount of curcumin that can be loaded into co-compressed chewing gums made from Health in Gum® as the base and flavored with 1.5% peppermint oil, (2) determine if addition of sweeteners can improve the yield strength and compressibility of the gums when examined by a texture analyzer, (3) examine the effect of temperature over a storage period of one month on the physical stability of the chewing gums, and (4) study the impact of substituting curcumin with its inclusion complex with SBE-β-CD on drug release. It was found that when flavored, Health in Gum® could load up to 25% curcumin by weight without compromising its masticatory properties. When tested for drug release, SBE-β-CD was found to significantly increase the amount of curcumin dissolved within 30 min. Despite poor drug release from gums loaded with insoluble curcumin, the fragmentation of the gums during mastication by the Erweka tester is nonetheless expected to produce a suspension for absorption in the lower GIT. This study demonstrated how modulating gum composition and storage conditions can impact the mechanical properties of chewing gums with high solids content. KEY WORDS: chewing gum; curcumin; cyclodextrin; textural analysis; tablet. INTRODUCTION Medicated chewing gums can be produced by conven- tional tablet compression technology using directly compress- ible gum bases, such as Health in Gum® [1]. When blended with active therapeutics, such as curcumin (CUR), chewing gum tablets (CGTs) could yield two potential therapeutic benefits: alleviate the suffering of head and neck cancer patients due to the pharmacological activity of CUR and the mechanical stimulation of salivary glands by chewing action [2–4]. Numerous studies have concluded that CUR chewing gums could be consumed alongside current head neck cancer treatment protocols to improve patient outcomes [2, 4, 5]. In a clinical study, it was shown that the poor bioavailability problem of CUR might be overcome by the oral transmucosal administration of 4 g of CUR twice a day in a gum formulation, which showed sustained CUR plasma concen- tration of at least 50 ng/mL [6–8]. High doses of CUR however are needed to attain such desirable plasma concen- trations [4, 9]. Unfortunately, loading chewing gums with high solids content, such as CUR powder, presents a significant challenge as it inadvertently impairs the mastication proper- ties of the co-compressed chewing gums. Consequently, patients are required to consume multiple low-dose chewing gums per day. Previously, we reported that 10% w/w CUR load is the upper limit for solids loading into Health in Gum® for it to retain gum-like mechanical properties [10]. Subsequent studies by our research group confirmed that the addition of liquid flavors up to 1.5% to the gum base significantly improved drug loading and chewability of the CGTs. There- fore, the first objective of the present study was to determine the upper limit to which CGTs could be loaded with CUR when formulated with 1.5% flavors. Flavored chewing gums 1 College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA. 2 College of Pharmacy, Hail University, Hail, Saudi Arabia. 3 DrugScan Pharmaceutical Services, Horsham, Pennsylvania, USA. 4 Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, Texas, USA. 5 To whom correspondence should be addressed. (e–mail: sami.nazzal@ttuhsc.edu) AAPS PharmSciTech ( # 2018) DOI: 10.1208/s12249-018-1174-1 1530-9932/18/0000-0001/0 # 2018 American Association of Pharmaceutical Scientists