Plastic and nonmetallic article shaping or treating: processes – Mechanical shaping or molding to form or reform shaped article – Shaping against forming surface
Reexamination Certificate
2001-12-03
2004-06-22
Lechert, Jr., Stephen J. (Department: 1732)
Plastic and nonmetallic article shaping or treating: processes
Mechanical shaping or molding to form or reform shaped article
Shaping against forming surface
C264S331210
Reexamination Certificate
active
06752953
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for manufacturing a non-gelatin hard capsule shell. The hard capsule shell is made by a heat-melting method which involves heating a capsule forming composition (preferably in powdery form) in a mold, followed by inserting a pestle into the mold to coat the melted capsule forming composition onto the pestle. The hard capsule shell is formed after hardened and dried, and removed from the pestle. The present invention also relates to a capsule forming composition which comprises a polymer and optionally a plasticizer. The polymer is preferred to be a cellulose or cellulose derivative, a polymer or copolymer of acrylate or acrylate derivative, a vinyl polymer, a polyolefin, poly(2-ethyl-2-oxazoline), or aginate. Finally, the present invention relates to an apparatus for making the hard capsule shell.
BACKGROUND OF THE INVENTION
Pharmaceutical capsules with telescopically engaged body and cap portions are called hard capsules or hard shell capsules. The most frequently used pharmaceutical capsules are generally made of gelatin. Optionally, plasticizer such as glycerin and sorbitol, opaque agent, dye, pigment and other additives can be blended in.
Gelatin is manufactured by the hydrolysis of animal by-products which contain collagen, which is usually found in animal bones, animal skins, and white animal connective tissues. The collagen-containing material is boiled in water, leaving behind the colorless or pale yellow protein which constitutes the hydrophilic colloid material of the gelatin.
The techniques for manufacturing the gelatin capsules are well developed. In general, a capsule molding pin is immersed in a gelatin aqueous solution and then withdrawn therefrom. The gelatin solution adhering to the pin is dried, thus obtaining the capsule shell. Some of the representative hard gelatin capsules include Warner-Lambert Company's PRE-FIT™, SNAP-FIT™, and CONI-SNAP™ series of hard gelatin capsules and Scherer's LOX-IT™ hard gelatin capsules.
However, because the primary sources of gelatin are from animals (such as bovine, pigs etc), gelatin-made capsules are not widely accepted by consumers. For example, Vegetarians, the Hebrews, and the Muslims do not ingest pigs and by-products of pigs. Also, Vegetarians and the Hindus will not eat beef or by-products of beef. These people are generally unwilling or feeling uneasy to utilize gelatin capsules for their medications or dietary supplements. Recently, there has been concerned about cross-species contamination. For example, the outbreak of bone spongiform encephalopathy, also known as BSE or “Mad Cow Disease,” suggests that a disease initially infested in cows can be transmitted to humans. Thus, the use of gelatin capsules becomes a concern and it is more desirable to replace gelatin capsule with capsules derived from other natural or synthetic sources.
Medical capsules using a base other than gelatin are also known in the art. Typically, capsules based on water-soluble cellulose derivatives are widely used. For example, in 1950, U.S. Pat. No. 2,526,683 to Murphy first described a process for preparing methyl cellulose medicinal capsules by a so-called “dip coating” or “dip molding” process. The process consists of dipping a capusle forming pin pre-heated to 40-85° C. into a cellulose ether solution kept at a temperature below the incipient gelation temperature (10-30° C.), withdrawing the pins at a predetermined withdrawal speed and then placing the pins in ovens kept at temperatures above the gelation temperature (45-85° C.), exposing the pins to a lower temperature first and then gradually to higher temperature until the film is dry. The dry capsule is then stripped, cut to size, and the body and caps are fitted together. The Murphy patent is the original patent for the manufacture of methyl cellulose capsule. Its drying process uses infrared lamps and cooling by air.
The methyl cellulose capsules according to Murphy's U.S. Pat. No. 2,526,683 have several advantages over conventional gelatin capsules, such as resistance to microorganisms and greater stability under extreme humidity conditions. However, these capsules failed to dissolve in the gastrointestinal fluid at body temperature in an acceptable time.
Sarkar's U.S. Pat. No. 4,001,211 descibe a medicinal capsule using thermal gelling cellulose ethers such as methyl cellulose and hydroxypropylmethyl cellulose. These cellulose ethers are soluble in cold water and insoluble in hot water. The viscosity of aqueous solutions decreases with the rise in temperature and then rapidly increases through a relatively narrow range of temperature with gel formation a few degrees above the temperature at which minimum viscosity is observed. Sarkar's capsules are prepared by a pin dip coating process by blending a water soluble methyl and C
2
-C
3
hydroxyalkyl cellulose ethers to achieve an essentially Newtonian dip coating solution. Blends of low viscosity methyl cellulose and hydroxypropylmethyl cellulose provide particularly suitable dip solution properties, gel yield strength, and capsule dissolution rates.
Muto's U.S. Pat. No. 4,993,137 is directed to the manufacture of capsules made from the improved methyl cellulose ether of Sarkar. Muto discloses a process for gelling the solution by dipping solution coated pins into thermally controlled water.
Grosswald et al.'s U.S. Pat. No. 5,698,155 describe a method and apparatus to manufacture pharmaceutical capsules which use an aqueous solution of a thermogelling cellulose ether composition and use capsule body pins and capsule cap pins as molds. The method involves heating the pins, dipping the pins into the cellulose-containing aqueous solution to cause the solution to gelatinize on the surface of the pins, removing the pins, and drying the gelatinized solution on the surface of the pins to form the capsule bodies and capsule caps.
Yamamoto et al.'s U.S. Pat. No. 5,756,123 discloses a capsule shell containing 79.6-98.7% by weight of a hydroxypropylmethyl cellulose (HPMC) as a water-soluble cellulose derivative base, 0.03-0.5% by weight of carrageenan as a gelling agent, and 0.14-3.19% by weight of a potassium ion and/or a calcium as a co-gelling agent. The capsule shell is prepared by blending the HPMC with carrageenan in the water to form an aqueous solution, and drying the aqueous solution to form a capsule shell using the conventional immersion molding method.
In the invention to be presented in the following sections, a novel heat-melting method for preparing hard capsule shell is provided. The method involves adding a capsule forming composition to a mold. The composition contains a polymer and optionally a plasticizer but does not contain any solvent. The polymer is not a gelatin. The capsule forming composition is heated inside the mold to become a melted solution. A pestle which can fittedly insert into the mold and which is also heated to above the melting temperature of the composition is then inserted into the mold with pressure to allow the melted composition evenly coated onto the pestle. The pestle with melted composition is then withdrawn from the mold and upon drying, the capsule is removed from the pestle. This method differs from the conventional dip coating method for no gelling solution or solvent is involved. The capsule shell formed by this method is cost-effective and does not have the common imperfections found in capsules made by conventional dip coating method, such as wrinkles, starred ends and corrugations.
SUMMARY OF THE INVENTION
The present invention provides a method for manufacturing a hard capsule shell. The method comprises: (1) adding a capsule forming composition to a mold having at least an opening shaped as a capsule cap or a capsule body; (2) heating the mold and a capsule forming pestle having a diameter smaller than the mold opening to a temperature which is above a melting temperature of the capsule forming composition; (3) applying pressure to insert the heated capsule forming pestle into the o
Chen Gan-Lin
Lee Chien-Yuan
Liu Cheng-Hsiung
Chao Fei-Fei
Lechert Jr. Stephen J.
Venable LLP
Yung Shin Pharmaceutical Co., Ltd.
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