(12) Patent Application Publication (10) Pub. No.: US 2006/0121066A1 Jaeger Et Al
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US 2006O121066A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0121066A1 Jaeger et al. (43) Pub. Date: Jun. 8, 2006 (54) SUCRALOSE FORMULATIONS TO MASK Publication Classification UNPLEASANT TASTES (51) Int. Cl. (76) Inventors: David Jaeger, Chester, VA (US); Jay A61K 3 1/7012 (2006.01) Dickerson, Midlothian, VA (US); A6II 3L/495 (2006.01) Annabelle Trimmer, Manakin Sabot, A6IR 9/00 (2006.01) VA (US) (52) U.S. Cl. ....................... 424/400: 514/53: 514/255.04 Correspondence Address: (57) ABSTRACT DARBY & DARBY P.C. P.O. BOX 5257 The present invention is directed to a pharmaceutically NEW YORK, NY 10150-5257 (US) acceptable taste masking liquid excipient base for adminis tration of a relatively large amount of unpleasant tasting (21) Appl. No.: 10/485,858 medicines. More particularly, the enhanced Sweetness and taste masking effect are produced by the addition of Sucral (22) Filed: Jan. 27, 2005 ose to the excipient base with maintenance of a pH from about 2 to about 5. The invention is further directed to medicinal compositions comprising such a liquid excipient Related U.S. Application Data base and unpleasant tasting medicines. Still further, the invention is directed to a method for taste masking unpleas (60) Provisional application No. 60/308.912, filed on Jul. ant tasting medicines through their incorporation into the 31, 2001. claimed liquid excipient bases. US 2006/01 21066 A1 Jun. 8, 2006 SUCRALOSE FORMULATIONS TO MASK from the group consisting of antihistamines, decongestants, UNPLEASANT TASTES antitussives, expectorants, antibiotics, antineoplastics, non steroidal anti-inflammatory drugs (NSAIDs) and analgesic 0001. This application claims priority under 35 U.S.C. S drugs. 1.119(e) to provisional application Ser. No. 60/308,912, filed Jul. 31, 2001, which is incorporated herein by reference in 0008. The invention further provides a method for taste its entirety. masking at least one unpleasant tasting pharmaceutically active compound comprising dissolving such unpleasant FIELD OF THE INVENTION tasting pharmaceutically active compound into a liquid 0002 The present invention is directed to a pharmaceu excipient base containing a sufficient amount of Sucralose to tically acceptable taste masking liquid excipient base for mask a bitter taste of any active ingredient, wherein the administration of a relatively large amount of unpleasant composition has a pH greater than 2.0 and less than 5.0. tasting medicines. More particularly, the enhanced Sweet ness and taste masking effect are produced by the addition DETAILED DESCRIPTION OF THE of Sucralose to the excipient base with maintenance of a pH INVENTION from about 2 to about 5. The invention is further directed to 0009. The present invention advantageously provides an medicinal compositions comprising such a liquid excipient enhancement of flavor masking with Sucralose. In particular, base and unpleasant tasting medicines. Still further, the by providing a Sweetening amount of Sucralose, i.e., an invention is directed to a method for taste masking unpleas amount of Sucralose sufficient to mask the bitter taste, at an ant tasting medicines through their incorporation into the acid pH (i.e., pH less than about 5.0) in an aqueous base claimed liquid excipient bases. excipient, the invention greatly masks the bad taste, particu larly bitter taste, of many actives. BACKGROUND OF THE INVENTION 0010. The present invention is based, in part, on the 0003 Pharmaceutically acceptable liquid excipient bases discovery that modulation of pH combined with the use of for administration of unpleasant tasting medicines are well Sucralose as a Sweetening agent produces Surprisingly Supe known in the art. A typical system is described in U.S. Pat. rior taste masking abilities—better than either manipulation No. 5,260,073 to Roger J. Phipps at column 7as including a produces alone and better than the combination of the two medicine, a solvent, a co-solvent, a buffer, a surfactant, a would be expected to produce. preservative, a Sweetening agent, a flavoring agent, a dye or pigment, a Viscosity modifier and water. The patent provides 0011 Sucralose is a chlorinated sucrose derivative, in several examples of each ingredient in the system. However, which three —OH groups are replaced by chlorine atoms. despite making the medicine more palatable, these compo Sucralose has a Sweet, Sugar-like taste. It is approximately sitions retain an unpleasant taste and have room for 600 times Sweeter than Sugar and is used as an artificial improvement. Sweetener. Sucralose displays a rapid onset of Sweetness and maintains a similar Sweetness duration to Sugar. 0004 Although liquid excipient bases and their many ingredients are well known, unpleasant tasting medicines 0012 Pharmaceutically acceptable taste masking bases alone or in combination still present challenges to one useful in this invention are preferably those incorporating skilled in the art to provide better taste masked products and, therein per 100 milliliters of base, about 50 to about 300 in certain instances, to provide taste masking for higher milligrams, preferably about 100 to about 200 milligrams, dosage amounts of unpleasant tasting medicines in Smaller most preferably 200 milligrams of sucralose. More or less amounts of vehicle. Sucralose may be used to achieve an acceptable balance of sweetness and effectiveness in bitter-masking. The pH of the liquid base is from about 2.0 to about 5.0. The preferred pH SUMMARY OF THE INVENTION range for formulations containing acetaminophen combined 0005 The present invention provides a pharmaceutically with pseudoephedrine hydrochloride, dextromethorphan acceptable taste masking liquid excipient base for adminis hydrobromide, chlorpheniramine maleate and bromphe tration of unpleasant tasting pharmaceutically active com niramine maleate is 4.0–5.0. The preferred pH range for pounds. The liquid base contains a Sufficient amount of formulations containing guaifenesin combined with pseu Sucralose to mask a bitter taste of any active ingredients doephedrine hydrochloride and/or dextromethorphan hydro dissolved therein and has a pH of less than about 5.0 and bromide is 2.0-4.0. In a specific embodiment the lower value greater than about 2.0. Lower pH and use of Sucralose as a is about 2.5 or 2.6; in another embodiment the upper value Sweetener achieves an unexpected Synergy of bitter taste is about 3.7. masking effectiveness. 0013 In accordance with the invention, pH of the base 0006 Pharmaceutically acceptable taste masking bases can be lowered by addition of acids, e.g., citric acid, or any useful in this invention are preferably those incorporating other pharmaceutically acceptable acid. Alternatively, pH is therein, per 100 milliliters of base, about 50 to about 300 established using a buffer system. Preferably the buffer is milligrams, preferably about 100 to about 200 milligrams, Sodium citrate/citric acid. However, any pharmaceutically most preferably 200 milligrams of sucralose. More or less acceptable buffer can be used, including phosphate, acetate, Sucralose may be used to achieve an acceptable balance of maleate, and any other acid or acid-salt. sweetness and effectiveness in bitter-masking. Preferably, 0014) Citrate buffering systems comprising, per 100 mil the pH of the liquid base is from about 2 to about 5. liliters of base, (i) about 200 to about 1800, preferably about 0007. The excipient base may be used to mask the 300 to about 1700 milligrams, most preferably 400 or 1600 bitterness of any active ingredient, including those selected milligrams of citric acid; and (ii) about 0 to about 200 US 2006/01 21066 A1 Jun. 8, 2006 milligrams, preferably about 50 to about 150 milligrams, properties at the dosage administration can be prepared. most preferably about 100 milligrams of sodium citrate are Placebo formulations, which lack an “active ingredient’ used to yield a pH in the range of about 2 to about 5. having a known pharmacologic activity, are also within the Preferably, the pH is established after the addition of active scope of the invention. An “active ingredient of a placebo ingredients and Sucralose. can be any non-active compound that takes the place of an 0.015 The pharmaceutically active compounds useful in active ingredient in the corresponding formulation. the practice of the present invention include antihistamines, 0019. The invention is best suited for formulations in decongestants, antitussives, expectorants, antibiotics, anti which the active is more stable at a pH less than 5.0. neoplastics, non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesic drugs such as acetominophen 0020. A non-limiting list of acceptable active ingredients and phenacetin. These materials are incorporated into the may include but is by no means limited to the following claimed liquid excipient base in amounts governed by the (where specific salts or esters are mentioned, it should be solubility of the material in such excipient base and such that understood to include other salt, ester, or free acid forms of conventional dosages thereof shall be in compliance with the drug): applicable FDA regulations. For example, materials highly 0021 l) antipyretic analgesic anti-inflammatory agents soluble in the liquid excipient base must not be incorporated (which are discussed in greater detail, with additional to the extent that a typical dose (such as one teaspoon) examples, below), including non-steroidal anti-inflamma contains more of Such material