Drug delivery system

Abstract: A drug delivery system in which a taste masked solid is suspended in a liquid carrier. The solid has been rendered hydrophillic and its density approximates that of the carrier liquid.

Description: Background of the Invention I. Field of the Invention The invention relates to the delivery of drugs which do not have a palatable taste and where it is undesirable to ingest said drugs in a solid state. Those of ordinary skill in the art would have expertise in taste masking drugs and related products. II. Description of the Prior Art Taste masking of drugs through the use of flavors is well known. However, flavoring ingredients are not sufficient to mask certain drugs and vitamins. Therefore, physical means have been developed to encapsulate or place in a chemical barrier these drugs to mask their undesirable taste characteristics. One such system which has been used for vitamins is disclosed in U.S. Patents 3,037,911; 3,080,292; 3,080,293; and 3,279,994. These methods produce products which are in beadlet form. Although these beadlets are effective for taste masking they can cause other difficulties with respect to certain drugs, and types of patients. For instance, patients who have problems taking solid dosage forms cannot utilize drugs produced by this beadlet process. Also, products, such as potassium chloride cannot effectively be taken in the beadlet form described by the prior art. Solid forms of potassium chloride are known to lay along the stomach or intestinal lining and ulcerate the stomach or intestinal wall. This ulceration or bleeding of the stomach is a highly undesirable side effect, especially for elderly patients. Thus, the treatment of one affliction causes the occurrence of other serious medical problems. BE-A-555932 describes a pharmaceutical composition comprising granules which contain the active agent and granules which contain a sweetening agent, wherein the different granules are connected by an eatable rubber. The granules containing the sweetening agent break immediately after contact with a liquid whereas the granules containing the active agent remain intact for a longer time. Furthermore, an aroma-providing agent is in the interstices between the different granules. The sweetening agent which is released into the liquid and the aroma-providing agent serves for masking the bad taste of the portion of active agent which already has been released into the liquid. EP-A-0 247 634 discloses a pharmaceutical in the form of small pellets having a taste- and odor-masking coating of a polymer practically insoluble in the mouth but readily soluble in an acid environment such as in the stomach. Said coating is comprised of a copolymer containing residues of (meth)acrylic esters and dimethyl aminoethyl (meth)acrylate, and an acid to solubilize the polymeric component (claim 1) which acid is selected from hydrochloric, nitric or sulfuric acid or from organic acids. For administration a premeasured dosage of the pellets is admixed with a food or other consumable material that is convenient and/or palatable to the patient. The invention relates to a pharmaceutical composition as defined in the claims. The present invention is advantageous since it allows the delivery of taste masked particles in a liquid form. It is also advantageous since it is economical and provides a product which has commercially desirable properties. Further, it is advantageous since it does not affect the active properties of the drug which is being delivered. Other advantages include being able to provide a solid drug form to those who cannot or will not take such drugs especially in large quantities. Finally, it should be noted that the composition of the invention meets a long felt need in the art. Description of the Preferred Embodiments The basic particles are produced by the methods disclosed by U.S. Patents 3, 037, 911; 3, 080, 292; 3, 080, 293; and 3, 279, 994. The beads produced by these processes are hydrophobic and therefore are unsuitable for use in formulating liquid suspensions. The beads are formed by pulverizing the active agents. The preferred active agent is potassium chloride which is pulverized to approximately 0,074 mm (200 mesh). Waxes or preferably a mixture of mono and diglycerides are melted to a molten state. For glycerides this is approximately 60-80 degrees C. The active agent is added to the melted mixture to form 40-60% of the total. The waxes and glycerides provide a taste masking coating over the active ingredient. In the present invention the densities of taste masking coating and the active agents are balanced. The total density of the product approximates that of a carrier liquid in which it is to be suspended and should preferably equal the density of the liquid into which it is to be suspended so as to form a drinkable suspension. Thus, if the product is to be suspended in water its overall density should approximate 1. Also, the ratio taste masking coating to active agent should be adjusted to reduce the solubility of the drug in the first 60 seconds. Flavors, modifiers and/or air are added to the mixture. The mixture is placed in a spinner which ejects liquid beads of the mixture which congeals as it cools. The beads are usually 0,149 - 0,59 mm (30 - 100 mesh). They can be compressed into tablet form. The taste masking coating is hydrophobic and so the beadlets will float on water. In order to render them hydrophilic and improve workability they are blended with surfactants or surface modifiers. A preferred surfactant is sodium lauryl sulfate which forms 0.25 to 2%, preferably 1%, of the beadlet by weight. The surfactant could be added either before or after the spinning of the beads. Also, additional colors and flavors can be added. Anticaking agents, such as, silicon dioxide are advantageously added and may comprise 1-3% by weight of the bead. Other materials which do not affect the basic properties of the material may be incorporated into the beadlets. It may be especially desirable to add pH modifiers which reduce dissolution initially but are neutralized by gastric pH, thereby, allowing rapid dissolution in the stomach. The beadlets may be packaged in single dose packages. When the patient is required to take a dose, the contents of the package are emptied into a glass of liquid. The beadlets form a suspension and do not dissolve immediately. However, they do dissolve fairly rapidly, i.e. no less than 90% within 15 minutes, in order to avoid gastric ulceration. The patient drinks the liquid. This system has a number of advantages. First, the active ingredient is taste masked as in the solid dosage forms. Second, the liquid can be taken by those who are not capable of taking a solid dosage form. Third, the side effects of the solid dosage form are not encountered. Fourth, gastric ulceration does not occur due to the rapid dissolution of the product. And fifth, a more acceptable consumer delivery system is achieved which encourages patient compliance in taking drugs, especially when large dosages are required. (EXAMPLE ONE) ALBUTEROL SULFATE CONTROLLED RELEASE LIQUETTE™ The Albuterol Sulfate Controlled Release Liquette™ is composed of: Albuterol Sulfate 7.5% Hydrogenated Vegetable Oil 92.5% The fatty base is melted and the albuterol sulfate powder is added carefully. The resulted melt is congealed by means of a spinning disc or other suitable spray congealing equipment. The resulting beads are blended with silicon dioxide and sodium lauryl sulfate to yield the liquette™. Albuterol Sulfate Beads 99.25% Silicon Dioxide 0.25% Sodium Lauryl Sulfate 0.50% (EXAMPLE TWO) THEOPHYLLINE CONTROLLED RELEASE LIQUETTE™ The Theophylline Controlled Release Liquette™ is composed of: Theophylline 40% Carnauba Wax 60% The wax base is melted and the theophylline powder is added carefully. The resulted melt is congealed by means of a spinning disc or other suitable spray congealing equipment. The resulting beads are blended with silicon dioxide and sodium lauryl sulfate to yield the liquette™. Theophylline Beads 99.25% Silicon Dioxide 0.25% Sodium Lauryl Sulfate 0.50% (EXAMPLE THREE) ANTACID LIQUETTE™ The antacid Liquette™ is composed of three separate type of beads which have the following composition: Bead #1 % w/w Magnesium Hydroxide 21.31 Aluminum Hydroxide Dried Gel 24.03 Na Azulene Sulfonate 0.19 Na Cu Chlorophyllin 0.21 Mono and Diglycerides 26.40 Carnauba Wax 26.40 Na Lauryl Sulfate 1.46 100.00 Bead #2 Scopolis 10% Extract 60.00 Mono and Diglycerides 39.90 FD&C Blue #1 0.06 FD&C Yellow #5 0.04 100.00 Bead #3 Na Cu Chlorophyllin 33.00 Stearic Acid 67.00 100.00 The base (carnauba wax, mono and diglycerides and stearic acid) is melted and the active ingredients are added carefully. The resulted melt is congealed by means of a spinning disc or other suitable spray congealinig equipment. The resulted beads are blended in the following ratio: Bead #1: 13.5 parts Bead #2: 2.0 parts Bead #3: 1.0 parts To the aforementioned blend, the following materials are added and the entire mixture is re-blended. Silicon Dioxide 0.50% Menthol Flavor 0.40% Peppermint Flavor 0.07% Sodium Lauryl Sulfate 0.50%

Claims: Claims for the following Contracting States : AT, BE, CH, LI, DE, FR, GB, GR, IT, LU, NL, SE A taste-masked pharmaceutical composition in the form of a suspension of hydrophilic particles in a liquid carrier, said particles comprising a pharmaceutically active agent characterized in that said particles are beads, wherein said beads comprise said active agent, a surfactant or a surface modifier and a coating selected from waxes and mixtures of monoglycerides and diglycerides, the density of said beads approximating that of said liquid carrier so as to form a drinkable suspension. The pharmaceutical composition of claim 1, characterized in that said active agent comprises potassium chloride. The pharmaceutical composition of claim 1 or 2, characterized in that said beads further comprise from 1% to 3% by weight of an anti-caking agent. The pharmaceutical composition of claim 3, characterized in that said anti-caking agent is silicon dioxide. The pharmaceutical composition of any of claims 1-4, characterized in that said beads further comprise one or more materials selected from colors, pH modifiers and flavors. The pharmaceutical composition of any of claims 1-5, characterized in that said surfactant is sodium lauryl sulfate and is present from 0.25% to 2% by weight, based on the total weight of the beads. The pharmaceutical composition of any of claims 1-6, characterized in that said beads dissolve by not less than 90% within 15 minutes following liquid carrier contact. The pharmaceutical composition of any of claims 1-7, characterized in that said liquid carrier is water and said surfactant is sodium lauryl sulphate Hydrophilic particles comprising a pharmaceutically active agent for the preparation of a suspension of said hydrophilic particles in a liquid carrier, characterized in that said particles are beads wherein said beads comprise said active agent, a surfactant or a surface modifier and a coating selected from waxes and mixtures of monoglycerides and diglycerides, the density of said beads approximating that of said liquid carriers so as to form a drinkable suspension. The hydrophilic particles of claim 9 being defined as in any of claims 2 - 7. The hydrophilic particles of claim 9 or 10, wherein said surfactant is sodium lauryl sulphate. Claims for the following Contracting State : ES A method for preparing a taste-masked pharmaceutical composition by forming a suspension of hydrophilic particles in a liquid carrier, said particles comprising a pharmaceutically active agent, wherein said particles are beads, wherein said beads comprise said active agent, a surfactant or a surface modifier and a coating selected from waxes and mixtures of monoglycerides and diglycerides, the density of said beads approximating that of said liquid carrier so as to form a drinkable suspension. The method of claim 1 characterized in that said active agent comprises potassium chloride. The method of claim 1 or 2, characterized in that said beads further comprise from 1% to 3% by weight of an anti-caking agent. The method of claim 3, characterized in that as said anti-caking agent silicon dioxide is used. The method of any of claims 1 to 4, characterized in that said beads further comprise one or more materials selected from colors, pH modifiers and flavors. The method of any of claims 1 to 5, characterized in that as said surfactant sodium lauryl sulphate is used and is present from 0.25% to 2% by weight, based on the total weight of the beads. The method of any of claims 1 to 6, characterized in that said beads dissolve by not less than 90% within 15 minutes following liquid carrier contact. The method of any of claims 1 to 7, characterized in that as said liquid carrier water is used and as said surfactant sodium lauryl sulphate is used. A method for preparing hydrophilic particles by pulverizing a pharmaceutically active agent, adding said agent to molten waxes or a molten mixture of mono- and diglycerides to provide a taste masking coating over the agent and blending said coating with surfactants or surface modifiers, characterized in that said particles are beads wherein said beads comprise said active agent, a surfactant or a surface modifier and a coating selected from waxes and mixtures of monoglycerides and diglycerides, the density of said beads approximating that of said liquid carrier so as to form a drinkable suspension. The method of claim 9 being defined as in any of claims 2 to 7. The method of claim 9 or 10, wherein as said surfactant sodium lauryl sulphate is used.

Inventors: PARADISSIS GEORGE N C O K V PH, PARADISSIS, GEORGE N. C/O K.V. PHARMACEUTICALS INC
Applicants: K V PHARMACEUTICALS INC, K.V. PHARMACEUTICALS, INC.
Application year: 1988
Main classification: A61K9
IPC codes: A61K9, A61K33