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Tablets & Capsules July 2014 9 used to deliver an API because its residence time in the mouth (average of 20 to 30 minutes) is greater than that of other dosage forms. Assessing the bitterness of molecules requires a standard for comparison and, by assigning quinine—a common bit- ter molecule—a bitterness ranking of 1, we can find the relative bitterness thresholds of other substances, as shown in Table 1. This article draws from the results of a study that used caffeine as the active ingredient to be taste-masked in a chewing gum matrix. Caffeine was selectred because it is a well-known, widely available substance used in a variety of applications. Chewing gum matrix The study was conducted using our company's propri- etary matrix, Health in Gum, which is a homogeneous, free-flowing mixture of powder excipients. It contains all the ingredients needed to produce compressed chewing gum: Gum base (an essential ingredient that provides chewability), sweeteners (polyols, such as sorbitol, iso- malt, or xylitol), softeners, and anti-caking agents that improve flowability and compressibility. The mixture runs on pharmaceutical tablet presses just like any other direct-compression formulation. Table 2 provides an example of the ingredients and their use levels that might be included in a medicated chewing gum that uses our company's matrix. As mentioned above, the flavoring of a chewing gum is key. Flavors not only impart taste but can also plasticize the chewing gum. The desired properties of the product are thus highly dependent on the flavor balance. All major flavor technologies can be used to produce med- icated chewing gum using our chewing gum matrix, including flavorings supplied as powders, liquids, or in an encapsulated form. The addition of a lipophilic liquid flavor is recom- mended to prolong the flavor sensation but only at a use level of less than 1 percent of the total; otherwise sticki- ness can develop due to over-plastification of the mixture during processing. Powder flavors can be added without limit, bearing in mind that the minimum recommended level of use of the gum mixture is approximately 85 per- cent. It is also important to recognize that different flavor technologies correspond to different manners of API release, as shown in Figure 1. Table 1 Relative taste indices of different substances [3] Sour substances Index Bitter substances Index Sweet substances Index Salty substances Index Hydrochloric acid 1 Quinine 1 Sucrose 1 NaCl 1 Formic acid 1.1 Brucine 11 1-Propoxy-2-amino- 5000 NaF 2 4-nitrobenzene Chloracetic acid 0.9 Strychnine 3.1 Saccharin 675 CaC 2 1 Acetylacetic acid 0.85 Nicotine 1.3 Chloroform 40 NaBr 0.4 Lactic acid 0.85 Phenylthiourea 0.9 Fructose 1.7 NaI 0.35 Tartaric acid 0.7 Caffeine 0.4 Alanine 1.3 LiCl 0.4 Malic acid 0.6 Veratrine 0.2 Glucose 0.8 NH 4 Cl 2.5 Potassium H tartrate 0.58 Pilocarpine 0.16 Maltose 0.45 KCl 0.6 Acetic acid 0.55 Atropine 0.13 Galactose 0.32 Citric acid 0.46 Cocaine 0.02 Lactose 0.3 Carbonic acid 0.06 Morphine 0.02 Table 2 Constituents of medicated chewing gum Standard formulation Use level (%) Active ingredient 10.00 Gum matrix PWD-04 85.20 Flavors 2.50 Lubricant 1.5 Glidant (silicon dioxide) 0.50 Intensive sweeteners 0.30 Figure 1 Flavor release versus chewing time Time Customer's flavor perception when liquid and microencapsulated flavors are combined Flavor impact Microencapsulated flavor Liquid flavor c-Belmarart_8-15_Masters 7/2/14 11:06 AM Page 9