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on eye 38 May 2018 Tablets & Capsules Hanna Bogner and Gernot Warnke JRS Pharma In this edition of Eye on Excipients, researchers present the results of a study that examined how dextrates can replace lactose in cetirizine tablets for the benefit of lactose-intolerant patients. Cetirizine dihydrochloride is a second-generation antihistamine that is used to treat hay fever, allergies, angioedema, and urticaria (hives). As an H1 antagonist, cetirizine relieves the symptoms of allergic reactions by temporarily blocking the action of histamine at the H1 receptors [1,2]. Cetirizine is one of the most com- mon H1 antihistamines, but many cetirizine tablets on the market con- tain lactose, making them unsuitable for lactose-intolerant patients [3]. Approximately 33 percent of the global population is affected by lac- tose intolerance—the inability to digest the milk sugar lactose. This condition is caused by a shortage of the enzyme lactase, which can lead to several gastrointestinal symptoms, including abdominal pain, bloating, diarrhea, gas, and nausea. Almost all infants produce sufficient amounts of lactase, but about 75 percent of adults have impaired lactase activity, especially in large parts of Asia and Africa. For this reason, it's important to study alternative excipients for the development of lactose-free drug products [4,5]. A potential substitute for spray- dried lactose in cetirizine tablets is dextrates, a directly compressible, water-soluble tablet filler and binder with comparable powder characteris- tics and functional tablet parameters to spray-dried lactose. This article presents the results of a study designed to determine whether dex- trates is a suitable substitute for lac- tose in marketed cetirizine tablets. The product used for the study was Emdex [6], which is monographed as dextrates in the USP. It is composed of 95 percent glucose monohydrate and 5 percent oligosaccharides resulting from the enzymatic hydro- lysis of starch. Reference product Reactine was selected as the study's reference product [7]. The white oblong film-coated tablets with breaklines measured 4 by 10 millimeters, weighed 120 milligrams, and sustained an average crushing strength of 79 newtons (Photo 1). In addition to 10 milligrams of ceti- rizine dihydrochloride, the Reactine tablets contained microcrystalline cellulose (MCC) and lactose mono- hydrate as filler-binders, silicon diox- ide as a glidant, and magnesium stea- rate as a lubricant. The tablets were coated with Opadry Y-1-7000, which is composed of hypromellose, tita- nium dioxide, and polyethylene gly- col (PEG) 400 [8]. Study design The cetirizine tablets were refor- mulated in both a lactose-based ver- sion to match the original reference product formulation as closely as possible, and in a lactose-free version that replaced the spray-dried lactose with dextrates. Both formulations were compressed into the same for- mat and size as the original tablets Photo 1: Reference product (Reactine) Parameter Dextrates (Emdex) Spray-dried lactose Particle size d 50 (µm) 190-220 130-160 Bulk density (g/L) 600-700 600-700 Tapped density (g/L) 700-800 700-800 Flodex index (mm) 4 4 Water solubility (g/L) 1,000 220 Table 1 Powder characteristics of dextrates and spray-dried lactose excipients