Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1995-01-18
2001-05-01
Harrison, Robert H. (Department: 1619)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S462000, C424S474000, C424S475000, C424S482000, C424S497000, C427S002210
Reexamination Certificate
active
06224911
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a process for preparing enteric coated pharmaceutical dosage forms, to the aqueous enteric coating dispersions suitable for use in the process, and to the enteric coated pharmaceutical dosage forms prepared by the process.
BACKGROUND OF THE INVENTION
The absorption of a drug as it passes through the alimentary canal can be controlled by coating the pharmaceutical with a substance which will at certain pH values retard release of the drug while at other pH values promote disintegration and/or leaching of the drug from the dosage form. For example, a coat comprised of an anionic polymer such as cellulose acetate phthalate prevents premature disintegration of the pharmaceutical in the acidic environment of the stomach and promotes rapid release of the drug in the intestine. Such a coat is commonly called an enteric coat (e.g., see U.S. Pat. No. 4,857,337 for a description of enteric coated aspirin dosage forms).
The enteric coat surrounds the core dosage form with a film which is hydrophobic at acidic pH values. At pH values below 4, the monolayers of the film are arranged in a compact alignment resistant to penetration by water and ions. However, at pH values of 5.8 and more basic the monolayers expand allowing the penetration of water and ions.
The enteric coat is applied by coating the pharmaceutical dosage form with a liquid enteric coating mixture in the presence of a sufficient amount of heat to vaporize the solvents. The mixture usually contains, in addition to an anionic polymer, a plasticizer or a combination of plasticizers. The plasticizers cross-link the polymer molecules together by hydrogen bonding which results in a lattice structure that adds tensile strength to the esoteric coat and promotes adhesion to the surface of the dosage form. The enteric coat can contain other ingredients such as surfactants, pigments, and fillers.
Organic solvents or aqueous mixtures of organic solvents are often used to prepare the enteric coating mixtures (e.g., see U.S. Pat. No. 4,377,568 for a description of aqueous alcoholic enteric coating dispersions). However, organic solvents have to be recycled and can result in contamination of the enteric coat. When water is used to prepare an enteric coating dispersion, a detackifier and glidant (e.g., talc) may be needed to avoid sticking or clumping of the pharmaceutical dosage forms during the application process. Constant and vigorous stirring is usually required to prevent the anionic detachifier/glidant from settling out. Because of the stirring, foaming may occur and antifoam agents may be necessary.
The solubility of an anionic polymer in an aqueous solvent can be increased by adding base (e.g., see Japanese Kokai No. J5 9193-382-A for a description of an aqueous enteric coating solution of carboxymethylethyl cellulose and base). However, the free base that is present in the solvent will also then be present in the resulting enteric coat and the capacity of the coat to resist disintegration in an acidic environment is reduced.
In addition to the various process-related problems which can occur during the application of the enteric coat, other problems may become apparent after the coat has dried (e.g., see Rowe, R. C. (1981)
J Pharm Pharmacol
33: 423). A sufficient amount of enteric coating material must be applied to the uncoated dosage form to assure the formation of an adequate enteric coat. However, as the amount of the enteric coating material is increased, problems may occur as a result of the internal stress that develops in the coat as it dries. For example, a common problem associated with enteric coated tablets is logo-bridging (i.e., the enteric coat pulls away from a tablet surface and the legibility of the monogram is lost). Typically, logo-bridging occurs when the weight gain due to the enteric coat exceeds 2-3% of the uncoated tablet weight.
The disclosure of the above and other documents referred to throughout this application are incorporated herein by reference.
SUMMARY OF THE INVENTION
This invention comprises a process for preparing enteric coated pharmaceutical dosage forms, which process comprises combining in water one or more anionic polymers, one or more plasticizers, one or more optional excipients, and a volatile base to form an aqueous enteric coating dispersion; and coating an uncoated pharmaceutical dosage form with the aqueous dispersion.
This invention also comprises an aqueous enteric coating dispersion suitable for use in the preparation of enteric coated pharmaceutical dosage forms, the dispersion comprising one or more anionic polymers, one or more plasticizers, one or more optional excipients, and a base which promotes the dispersion of the anionic polymers in water but readily vaporizes during the coating process.
This invention also comprises an enteric coated pharmaceutical dosage form prepared by the process of this invention.
ADVANTAGES OF THE INVENTION
The process of this invention produces an enteric coat which is free of organic solvents, detackifiers, glidants, and antifoam agents. In addition, because a volatile base is used in the process to promote the solubility of the anionic polymer in the aqueous enteric coating dispersion, the resulting enteric coat does not contain free base.
The process of this invention produces enteric coated tablets that at 6 to 15% weight gain pass USP enteric coating specifications for disintegration and dissolution and do not exhibit logo-bridging.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
Unless otherwise stated, the following terms used in the specification and claims have the meanings given below:
All percentages refer to percentages by weight.
The term “volatile base” means a base which which will readily vaporize under the conditions used for coating the uncoated dosage form.
The term “aqueous dispersion” or “aqueous enteric coating dispersion” means a mixture of enteric coating material dispersed in a solvent consisting essentially of water.
The term “enteric coating material” means the non-aqueous ingredients that are present in the aqueous enteric coating dispersion and the materials which comprise the enteric coat. For the process of this invention such materials can include anionic polymers, plasticizers, and optional excipients.
The term “pharmaceutically acceptable” means that which is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary use as well as human pharmaceutical use.
The term “pharmaceutical dosage form” means a dosage form of a drug (e.g., tablet, powder, capsule, and the like) which is pharmaceutically acceptable, as defined above, and which possesses the necessary and desirable characteristics of a dosage form acceptable for administration to a patient (e.g., a tablet of acceptable hardness, dissolution, stability, and a size and weight practical for oral administration).
The term “optional excipients” means that excipients may or may not be present. For example, “combining in water one or more anionic polymers, one or more plasticizers, one or more optional excipients, and a volatile base” means that combining the excipients may or may not be carried out in order for the described process to fall within the invention.
The term “uncoated” when referring to a dosage form means that the dosage form does not have an enteric coat.
Materials
Suitable anionic polymers for the enteric coating of this invention are insoluble in acidic environments (e.g., gastric juice) but are soluble at pH 5.5 and upwards. Such polymers include cellulose acetate phthalate, methacrylate-base polymers, cellulose acetate, trimellitate, hydroxypropyl methylcellulose phthalate, and the like. Suitable methacrylate-based polymers include Eudragit® L and Eudragit® S, anionic polymers synthesized from methacrylic acid and an acrylate. Specific methacrylate-based polymers include Eudragit® L 100, which is synthesized from methacrylic acid and methyl methacrylate and has a ratio of free carboxyl groups to ester groups of approxim
Chowhan Zakauddin T.
Vo Patrick H.
Harrison Robert H.
Heller Ehrman White & McAuliffe LLP
Syntex (U.S.A.) LLC
LandOfFree
Process for the preparation of enteric coated pharmaceutical... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of enteric coated pharmaceutical..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of enteric coated pharmaceutical... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2480045