ORIGINAL ARTICLE Design and Evaluation of the Release Characteristics of Caffeine-Loaded Microcapsules in a Medicated Chewing Gum Formulation Nima Mohammadi 1 & Mohammad Reza Ehsani 1 & Hossein Bakhoda 2 Received: 24 January 2018 /Accepted: 9 April 2018 /Published online: 14 April 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The aim of this study was to microencapsulate caffeine by the emulsion technique, trying to control its release from a medicated chewing gum. Three formulations were prepared using alginate, alginate-starch, and alginate-starch with chitosan coating as the wall materials. These microcapsules were characterized with regard to the morphology studied by using an optical microscope and scanning electron microscopy (SEM), particle size, and encapsulation efficiency. The microcapsules were then incorporated into the chewing gums. The chewing gums were characterized by thermal behavior (by differential scanning calorimetry [DSC]), texture profile analysis [TPA], and sensory evaluation. Furthermore, the release of caffeine from the chewing gum was studied in vitro using the masticatory simulator and in vivo by a chew-out study. The microcapsules revealed a spherical form and high encapsulation efficiency, representing the success of the technique. The outcomes indicated that it is possible to encapsulate caffeine with the techniques employed and the microcapsules prolonged the release of caffeine throughout mastication. The chewing gum containing alginate-starch with chitosan-coated microcapsules showed the great potential of the microcapsule in controlling the release of the caffeine from the chewing gum, thereby delaying its bitterness. Keywords Texture profile analysis . Differential scanning calorimetry . Masticatory simulator . Optical microscope . Chewing simulator Introduction Human beings belonging to every culture have chewed types of gum and gum-like substances from ancient times. Medicated chewing gum (MCG) is not a distinctive form, but is the gum base with drug(s) added to it [1, 2]. Medicated chewing gums are defined as a Bsolid preparation with a base consisting mostly of gum which is designed to be chewed and not to be swallowed, giving a gradual steady release of the drug contained.^ It may be used both for local treatment of oral cavity disease and for sys- temic delivery [1, 3]. In 1869, the first patent for commercial chewing gum was introduced by a dentist. He regarded chewing gum to be not only a delicious confectionery but also as having a beneficial function as a dentifrice [4, 5]. The first medicated chewing gum BAspergum^ was launched in 1924. It contained acetylsalicylic acid for a headache and is still available on the market. The successful background of nicotine chewing gum in the 1980s has resulted in more popularity of chewing gum as a drug delivery system [6]. Recently, specialized attempts have been made to control the release of various components in chewing gum. In particular, efforts have been designed to retard the release of bioactive in medicated chewing gum formulations to thereby expand the pleasing chewing time of the gum [7]. Delaying the release of drugs can also prevent an unwanted overwhelming burst of bioactive during the initial chewing period [8]. Caffeine as a stimulant may be added to chewing gum; however, significant taste problems may possibly occur, given the bitter nature of caffeine [9]. Hence, a prolonged or retarded release of caffeine could allow for the use of caffeine in chewing gum. Thus, the gradual release may allow consumers to more easily endure caffeine and not cause gastrointestinal distress [10, 11]. Therefore, the physical modification of caffeine by microencap- sulation is a new approach to address its bitterness and delivery at particular sites under controlled situations [12]. * Mohammad Reza Ehsani mr.ehsani2015@gmail.com 1 Department of Food Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Department of Agricultural Mechanization, Science and Research Branch, Islamic Azad University, Tehran, Iran Food Biophysics (2018) 13:240–249 https://doi.org/10.1007/s11483-018-9530-y