United States Patent [19] [11] Patent Number: 4,704,278 Wu Et Al

United States Patent [19] [11] Patent Number: 4,704,278 Wu et al. [45] Date of Patent: :1: Nov. 3, 1987 [54] FLUIDIZED MAGALDRATE SUSPENSION 4,117,116 9/1978 Buehler et a1. .................... .. 424/158 [75] Inventors: Chien-Chin Wu, Wilmington, Del.; OTHER PUBLICATIONS Gerald L‘ Renter’ Plattsburgh’ NY‘ Handbook on Nonprescription Drugs, Fifth Edition [73] Assignee: American Home Products Corp (Del), (1977), p. 16, American Pharmaceutical Assoc, Wash. New York, N.Y. D.C. [ * 1 Notice The portion of the term of this patent Primary Examiner-Frederick E. Waddell subsequent to Jun. 30, 2004 has been disclaimed. [57] ABSTRACT , [211 App], N03 395,012 An aqueous antacid composition of magaldrate gel and _ . a process for preparing same are described by the inven [22] F11e d'' A ug' 8 ’ 1986 t1on.- The composltlon- - is prepared from and contains _ . precipitated and undried magaldrate gel and a ?uidizing Related U‘S' Apphcatlon Data of a ?rst and second ?uidizer. On fluidizer is provided [63] Continuation of Ser. No. 661,648, Oct. 17, 1984, aban~ by an aluminum hydroxide gel having colloidal proper doned’ ties and the second by a pharmaceutically acceptable [51] Int. (:1.4 ............................................ .. A61K 33/08 citrate ion source including citric acid- The Process and [52] US. Cl. .............. .. 424/157; 424/158 compositiw are characterized in Providing a ?uid, [5 8] Field of Search .............................. .. 424/157, 158 resuspendlble, pharmaceutically elegant suspension POS _ ' sessing high antacid capacity and stability at even ele [56] References cued vated magaldrate concentrations in addition to the abil U.S. PATENT DOCUMENTS ity to ?uidize stiff, paste-like magaldrate gel cakes. 4,112,072 9/1978 Rubino et a1. .................... .. 424/158 4,115,553 9/1978 Rubino et a1. .................... .. 424/158 3 Claims, No Drawings 4,704,278 1 2 colloidal properties and a loss of ?uidity or mobility. FLUIDIZED MAGALDRATE SUSPENSION Even where ?uidity is initially maintained or achieved, further requirements of pharmaceutically acceptable This is a continuation of application Ser. No. 661,648, aqueous antacid suspensions call for a smooth (non ?led Oct. 17, 1984, now abondoned. gritty) mouth feel and maintenance of a gel structure for both suspendibility and resuspendibility. In general, BACKGROUND OF THE INVENTION resuspendible, aqueous antacid suspensions are typically 1. Field of the Invention de-?occulated products which contain a de?occulant This invention relates to resuspendible, pharmaceuti or suspending agent to arrest or control further agglom cally elegant high concentration, low viscosity, aqueous eration or ?occulation and settling. In the absence of a ' antacid suspension dosage forms for oral administration de?occulant or suspending agent type additive, the and to methods for their preparation and use. antacid in a suspension forms a hard cake or a gel struc 2. Decription of the Antacid Art ture which can no longer be resuspended with its origi Antacids are widely used in the treatment of gastroin nal desirable characteristics. The formation of such a testinal disorders. Their effectiveness in promoting the cake or gel structure is independent of antacid concen healing of gastric and duodenal ulcers has been well tration except for low antacid concentration. documented. Essentially, antacids exert their positive The de?occulants and suspending agents have been effects by neutralizing the gastric acid secreted in the frequently included in the formulation of aqueous ant stomach. When the pH of stomach contents is raised acid suspensions containing solid antacid concentrations above 3, most gastric acid is neutralized and the proteo 20 in the range of about 6 to 12 percent to prevent caking. lytic activity of pepsin is inhibited. The recent elevation With the growing interest in providing antacid suspen of antacids to a major therapeutic role, particularly in sion dosage forms with a greater acid neutralizing ca ulcer therapy, rather than a merely pallative role, has pacity, means were sought to provide highly concen emphasized the importance of providing antacid prod trated but fluid systems. ucts featuring a high neutralization (and buffer) capac 25 US. Pat. No. 3,579,634 describes an antacid composi ity as well as a rapid rate of gastric acid neutralization. tion containing as the essential ingredients an antacid These features particularly that of rapid rate of neutral and a water dispersible, colloidal anionic ether or ester ization to the neutralization capacity of the antacid derivative of a low polymer of a monosaccharide as a de?ne the more effective antacid in vivo since it is less gelation agent, the gelation agent being such that a likely that unconsumed antacids will be removed by 30 thickened gel-like consistency occurs upon interaction normal gastric emptying. of the composition with gastro-intestinal mucous so as Most antacids are available in both liquid and solid to adhere thereto. The gelation agent in vitro is de dosage forms. The liquid antacids, as aqueous suspen scribed as providing ?uidity to concentrated suspen sions, are, generally, more effective than the same ant sions, and the starting actacid may be selected from acids in solid dosage forms and are more commonly powder, granule or paste forms of certain calcium, alu prescribed in the hospital. The greater effectiveness of minum, magnesium, sodium and bismouth antacids. The liquid antacids is partially due to the large surface area antacid suspension compositions disclosed therein ap available in liquid suspensions to react with gastric acid pear to initially require milling, high energy agitation or and partially due to the great amount of colloidal parti homogenization to eliminate the grittiness of the antacid cles in aqueous suspension which can more easily reach ingredient. the affected area where treatment is needed. Moreover, In U.S. Pat. No. 3,591,680, high concentration ant aqueous suspensions of undehydrated antacids are more acid suspensions are disclosed containing about 25 to 50 reactive than dry or solid antacids. percent weight/volume of certain selected solid antacid While liquid antacids possess these advantages, the materials suspended in an aqueous vehicle containing same require administration of relatively large volumes 45 certain speci?ed suspending agents of which a de?nd of liquid suspension. The ingestion of such large vol hydroxypropyl cellulose is preferred. While these sus umes is inconvenient, however, making the normal pension are said to provide stable and palatable, high problem of assuring patient compliance outside the concentration suspensions, the preferred composition is hospital environment even more difficult. Since high stated to provide only a minimum of 2 months of contin dose regimes of liquid antacid have recently been ued ?uidity and pourability. Such standards are not shown to be effective both in promoting the healing of acceptable for a commercial product in which shelf life duodenal ulcers and in preventing the acute upper gas stability should extend for at least 1-2 years. trointestinal bleeding in critically ill patients, the use of US. Pat. No. 3,347,744 discloses a high concentration regular liquid antacid suspensions with the usual solid magnesium hydroxide suspension containing up to 30% antacid content in the 6-12 percent range has become of that antacid with a cellulosic suspending agent and even more impractical for such therapeutic indications. submicroscopic silica. The suspension is said to avoid The most widely used antacids can be described as the clumping and caking common among even lower mineral type, insoluble inorganic salts that are hydrated, concentration magnesium hydroxide suspensions, al possess colloidal properties, and contain, for example, though there is no disclosure that the suspension is aluminum, magnesium, bismouth and the like. Com thereby rendered more ?uid. pounds of the described mineral variety in their freshly More recently, in US Pat. No. 4,117,116, there is prepared, hydrated form and in suspensions therefrom disclosed a method for lowering the viscosity of a com provide some of the characteristics desired in an ant mercially available aqueous antacid gel cake to render acid. To provide liquid antacids with a high neutraliza the same pumpable in the production environment. The tion capacity it is necessary to increase the solids con 65 gel cake represents a magnesium hydroxide antacid, an centration of the antacid components. Such increases in aluminum hydroxide antacid or a mixture thereof and concentration, however, are accompanied at higher the antacid is 25-35% weight by weight of the gel cake levels with exponential increases in viscosity, a loss in before processing. The method comprises mixing into 4,704,278 3 4 the gel cake a ?uidizing agent selected from acacia, equivalent of not less than 18.0 percent and not more citric acid, sodium citrate, sodium lauryl sulfate or dioc than 26.0 percent of aluminum oxide (A1203). tyl sodium sulfosuccinate and the ?uidizing agent The preparation of magaldrate is described in US amounts to 0.l—4% of the ?nal total mixture. Pat. No. 2,923,660. A commercially suitable procedure It is an object of this invention to provide magaldrate, is described in said patent, for example, beginning in aqueous antacid suspensions with high antacid capacity column 2, line 40, although to maintain a low sodium and good mouth feel characteristics. content for the ?nal product, the use of potassium

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