title: Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression.
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 compressible 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/cm2) 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 a 23factorial 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/cm2and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm2, 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.
authors.affiliation: 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.
authors.forename: Kishor V
authors.initials: KV
authors.lastname: Kande
authors.affiliation: 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.
authors.forename: Darsheen J
authors.initials: DJ
authors.lastname: Kotak
authors.affiliation: 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.
authors.forename: Mariam S
authors.initials: MS
authors.lastname: Degani
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, Mendeleev Center, 199034, St. Petersburg, Russia.|Laboratory of Artificial Sensory Systems, ITMO University, Kronverkskiy pr., 49, 197101, St. Petersburg, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kirsanov
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, Mendeleev Center, 199034, St. Petersburg, Russia.|Laboratory of Artificial Sensory Systems, ITMO University, Kronverkskiy pr., 49, 197101, St. Petersburg, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Legin
authors.affiliation: 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. pvdevarajan@gmail.com.
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000284:Administration, Oral; D019245:Compressive Strength; D005079:Excipients / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D055772:Green Chemistry Technology / Q000379:methods*; D006244:Hardness; D007785:Lactose / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D008353:Mannitol / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D008872:Microwaves; D012995:Solubility; D013607:Tablets; D013649:Taste; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: D005079:Excipients; D013607:Tablets; D047392:beta-Cyclodextrins; D008353:Mannitol; D007785:Lactose
keywords: Lamotrigine; microwave irradiation; orally disintegrating tablet; taste masking; β-cyclodextrin