title: Application of general multilevel factorial design with formulation of fast disintegrating tablets containing croscaremellose sodium and Disintequick MCC-25.
abstract: Despite the popularity of orally fast disintegrating tablets (FDTs), their formulation can sometimes be challenging, producing tablets with either poor mechanical properties or high disintegration times. The aim of this research was to enhance the properties of FDTs produced by direct compression to have both sufficient hardness to withstand manual handling, and rapid disintegration time. General multilevel factorial design was applied to optimise and evaluate main and interaction effects of independent variables (i) disintegrant concentration, (ii) % filler (Disintequick MCC-25) to mannitol on the responses hardness, tensile strength and disintegration time. In this experiment mannitol was used as a diluent, Disintequick MCC-25 (to best of our knowledge there is no publication available yet for its use with FDTs) was termed in this study as a filler and croscaremellose sodium was used as the superdisintegrant. Seven formulations were prepared following a progressive two-stage approach. Each stage involved the change in the ratio of excipients (Mannitol:Filler) (1:0), (1:0.25), (1:0.50), (1:1), (0.50:1), (0.25:1), (0:1) w/w and concentration of superdisintegrant (1%, 3%, 5%, 7%, 10% w/w). All FDTs were tested for different parameters such as diameter, hardness, tensile strength, thickness, friability and disintegration time. The results of multiple linear regression analysis show a good degree of correlation between experimental (R(2):0.84, 0.94, 0.91) and predicted response (R(2):0.83, 0.96, 0.95) for hardness, tensile strength and disintegration time respectively. The optimum formulations (regarding disintegration time with acceptable hardness and friability properties) consisted of: (i) 5% w/w disintegrant and 20% w/w filler to mannitol, showing a disintegration time of 30s, a hardness of 66.6N (6.8 kg/cm(2)) and friability of 2.2%; (ii) 7% or 10% w/w disintegrant with 33.33% w/w filler to mannitol, showing disintegration time of 84 s (for 7% disintegrant) and 107 s (for 10% disintegrant), hardness of 73.86N (for 7% disintegrant) and 72.68N (for 10% disintegrant) and friability of 1.44 (for 7% disintegrant) and 1.15% (for 10% disintegrant).
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Solaiman
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK.
authors.forename: Ammar Said
authors.initials: AS
authors.lastname: Suliman
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Shinde
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK.
authors.forename: Sidra
authors.initials: S
authors.lastname: Naz
authors.affiliation: Sunderland Pharmacy School, Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK. Electronic address: amal.elkordy@sunderland.ac.uk.
authors.forename: Amal Ali
authors.initials: AA
authors.lastname: Elkordy
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D004339:Drug Compounding; D006244:Hardness; D008353:Mannitol / Q000737:chemistry; D012995:Solubility; D013314:Stress, Mechanical; D013607:Tablets / Q000737:chemistry*; D013718:Tensile Strength
chemical_list: D013607:Tablets; D008353:Mannitol; D002482:Cellulose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose
keywords: Disintegration time; Fast disintegrating tablets; General multilevel factorial design; Tablet hardness; Tensile strength