p-ISSN 1693-5683; e-ISSN 2527-7146 121 Vol. 20, No. 2, November 2023, pp. 121-129 Research Article Optimization of Crospovidone and Copovidone in Fast Disintegrating Tablet (FDT) Diphenhydramine HCl Using Factorial Design Aldo Christian Jonathan, Agatha Budi Susiana Lestari * Faculty of Pharmacy, Sanata Dharma University, Campus III, Paingan, Maguwoharjo, Depok, Sleman Yogyakarta, 55282, Indonesia https://dx.doi.org/10.24071/jpsc.006396 J. Pharm. Sci. Community, 2023, 20(2), 121-129 Article Info ABSTRACT Received: 16-05-2023 Revised: 19-06-2023 Accepted: 04-07-2023 *Corresponding author: Agatha Budi Susiana Lestari email: a_budi@usd.ac.id Keywords: Copovidone; Crospovidone; Diphenhydramine HCl; Factorial design; Fast disintegrating tablet; Diphenhydramine HCl is a drug used to treat motion sickness. Treatment of motion sickness needs rapid onset for successful therapy. Fast Disintegrating Tablet (FDT) is one dosage form that provides fast onset. The purpose of this study was to identify the dominant factors of crospovidone and copovidone, their interactions, and discover the optimum composition area to produce a FDT dosage form with optimum parameters involving hardness, friability, disintegration time, wetting time, and water absorption ratio. This study was experimental and used a factorial design. The result showed that copovidone significantly influenced friability, disintegration time, wetting time, and water absorption ratio, while their interactions significantly influenced the hardness of FDT diphenhydramine HCl. At the level studied, the optimum composition area was found, which can be predicted as a diphenhydramine HCl FDT dosage form formula. INTRODUCTION Diphenhydramine HCl is the first class of antihistamine drugs that can be used for the treatment of nausea and vomiting (Katzung et al., 2012), included in BCS class I with high solubility and permeability (Jyothi et al., 2013). The mechanism of action of diphenhydramine HCl is to compete with histamine to occupy H1 receptors. Diphenhydramine HCl works as an anticholinergic by blocking the passage of impulses through parasympathetic nerves (Whelan and Apfel, 2013). Tablets are the most widely used dosage form based on their ease and convenience of use. However, the use of conventional oral tablets must be assisted with certain media, for example, water, to help swallow. Water, which is not always available when traveling, limits the use of conventional oral tablets. To overcome this problem, a modification of conventional oral tablet formulations was carried out into the FDT (Fast Disintegrating Tablet) dosage form. One of the advantages of FDT is their fast disintegration time, and their use is more practical compared to conventional oral tablets. The FDT dosage form can disintegrate in the mouth in less than 30 seconds (Food and Drug Administration, 2008). The fast disintegration time will break the tablet into smaller particles in a short time. The small particle shape will increase the solubility of the dosage form, and with high solubility, it will support the rapid onset of the drug so that the resulting effect will be faster. Drugs that have high solubility and permeability have a good prospect of being developed into FDT dosage forms. In order to obtain an optimal FDT dosage form, it is necessary to select the appropriate manufacturing method and materials. In this study, diphenhydramine HCl was formulated in FDT using crospovidone as a superdisintegrant and copovidone as a binder made by the direct compression method. Crospovidone is widely used as an additive in a formulation to increase the disintegration time of tablets because it has more crosslinks compared to other superdisintegrants. This causes crospovidone to quickly experience swelling without gelling (Mohanachandran et al., 2011). Crospovidone is known to have been used successfully as a