Research Article Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression Kishor V. Kande, 1 Darsheen J. Kotak, 1 Mariam S. Degani, 1 Dmitry Kirsanov, 2,3 Andrey Legin, 2,3 and Padma V. Devarajan 1,4 Received 12 October 2016; accepted 29 November 2016 ABSTRACT. Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly com- pressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm 2 ) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a2 3 factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ∼3 to ∼5 kg/cm 2 and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/ cm 2 , DT < 30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology. KEY WORDS: Lamotrigine; microwave irradiation; orally disintegrating tablet; taste masking; β- cyclodextrin. INTRODUCTION Orally disintegrating tablets (ODTs) rapidly disintegrate in the mouth to provide an in situ dispersion enabling ease of administration. ODTs have thereby created a revolution as patient-friendly alternatives to the conventional tablets and capsules, especially for geriatric patients and the dysphagic (1,2). Balancing two opposing requirements, namely, rapid disintegration time (DT) and adequate hardness, coupled with good palatability is the major challenge in ODT development. Lyophilization was among the first processes reported for ODT development, wherein freeze drying of aqueous dispersions filled into blister alveoli cavities enabled the formation of porous tablets (3–5). Vacuum drying followed as an alternative to freeze drying (6). Nonetheless, while rapid disintegration was achieved, both processes resulted in porous fragile structures. An adapted cotton candy process produced floss-like rapidly dissolving crystal- line structures, which enabled ODTs with rapid DT, but could not overcome the limitation of poor strength (7). This process, moreover, involved high temperatures, further limit- ing drug candidates that could be incorporated (8). Wet molding technology, which involves moistening the powder blend with a hydroalcoholic solvent followed by 1 Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), N.P. Marg, Matunga (E), Mumbai, 400019, Maharashtra, India. 2 Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, Mendeleev Center, 199034, St. Peters- burg, Russia. 3 Laboratory of Artificial Sensory Systems, ITMO University, Kronverkskiy pr., 49, 197101, St. Petersburg, Russia. 4 To whom correspondence should be addressed. (e-mail: pvdevarajan@gmail.com) AAPS PharmSciTech ( # 2016) DOI: 10.1208/s12249-016-0683-z 1530-9932/16/0000-0001/0 # 2016 American Association of Pharmaceutical Scientists