CA1163196A - Aqueous spray-coated asa tablet - Google Patents
Aqueous spray-coated asa tabletInfo
- Publication number
- CA1163196A CA1163196A CA000382866A CA382866A CA1163196A CA 1163196 A CA1163196 A CA 1163196A CA 000382866 A CA000382866 A CA 000382866A CA 382866 A CA382866 A CA 382866A CA 1163196 A CA1163196 A CA 1163196A
- Authority
- CA
- Canada
- Prior art keywords
- hydroxypropyl methylcellulose
- asa
- tablet
- weight
- uncoated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Abstract
ABSTRACT OF THE DISCLOSURE
A method for preparing an easily-swallowed, powder-free, gastric-disintegrable and thinly coated ASA tablet, which does not have the characteristic ASA taste, does not produce the esophageal discomfort of an uncoated ASA tablet and does not disintegrate in the stomach materially slower than the uncoated ASA tablet, which comprises aqueous spray-coating hydroxypropyl methylcellulose onto all exterior surfaces of an ASA tablet, the amount of hydroxypropyl methylcellulose being between 0.5 and 2.0 parts by weight per 100 parts by weight of the ASA tablet. An aqueous solution of 2% to 15% by weight of hydroxypropyl methylcellulose and about 15% to 25% w/w of a plasticizer based on hydroxypropyl methylcellulose is sprayed onto uncoated ASA tablets in a slowly rotating baffled pan in a chamber equipped to measure and control both inlet and outlet air flow rates and both inlet and outlet air temperatures, said air flow rates and temperatures being sufficient to insure rapid evaporation of the water and to provide an evenly-applied thin coating of hydroxypropyl methylcellulose onto the uncoated tablets without causing their decomposition and/or physical disintegration. Preferred pan-rotation speeds, inlet and outlet air flow rates and temperatures are given. Other aspects of the invention are said thinly-coated tablets and said coated tablets when produced by said aqueous spray-coating method.
A method for preparing an easily-swallowed, powder-free, gastric-disintegrable and thinly coated ASA tablet, which does not have the characteristic ASA taste, does not produce the esophageal discomfort of an uncoated ASA tablet and does not disintegrate in the stomach materially slower than the uncoated ASA tablet, which comprises aqueous spray-coating hydroxypropyl methylcellulose onto all exterior surfaces of an ASA tablet, the amount of hydroxypropyl methylcellulose being between 0.5 and 2.0 parts by weight per 100 parts by weight of the ASA tablet. An aqueous solution of 2% to 15% by weight of hydroxypropyl methylcellulose and about 15% to 25% w/w of a plasticizer based on hydroxypropyl methylcellulose is sprayed onto uncoated ASA tablets in a slowly rotating baffled pan in a chamber equipped to measure and control both inlet and outlet air flow rates and both inlet and outlet air temperatures, said air flow rates and temperatures being sufficient to insure rapid evaporation of the water and to provide an evenly-applied thin coating of hydroxypropyl methylcellulose onto the uncoated tablets without causing their decomposition and/or physical disintegration. Preferred pan-rotation speeds, inlet and outlet air flow rates and temperatures are given. Other aspects of the invention are said thinly-coated tablets and said coated tablets when produced by said aqueous spray-coating method.
Description
~ :~631~
This invention relates to a coated acetylsalicylic acid tablet and its preparation. In particular, the invention relates to an aqueous spray-coating method of preparing an easily-swallowed, powder-free and gastric-disintegrable acetylsalicylic acid tablet and the tablet produced thereby.
Acetylsalicylic acid tablets historically have been difficult to film coat as they are friable~ dusty, and easily dissolved by water and organic solvents. Acetylsalicylic acid itself, hereinafter referred to as ASA or by its trade mark Aspirinl is readily decomposed by moisture and heat. Successful films have been applied from organic solvents using air as well as airless spray pro-ces~ing primarily because of the low flash points and rapid evaporation of the solvents involved.
S.F. Jeffries United States Patent 3,149,040, issued September 15, 1964,shows thin film coating of tablets with a particular mixture of cellulose acetate phthalate, a polyoxyethylene derivative of polypropylene glycol and plastici~er, said mixture applied in a non-aqueous system. No such coated Aspirin tablets are shown. Moreover, non-aqueous coating systems are now un-desirable from an environmental standpoint.
J.L. Anderson et al. United States Patent 3,341,416, issued September 12, 1967, discloses the encapsulation of minute particles of Aspirin in ethyl-cellulose, using a cyclohexane solu~ion of the latter. The encapsulated par-ticles are said to provide "a minimum amount of release" of Aspirin l'in the stomach" and a continuing release of Aspirin "slowly all along the extent of the intestinal tract."
E.H. Gans et al. United States Patent 3,388,041, issued June 11, 1968, teaches the preparation of a high dosage sustained release tablet containing Aspirin which comprises granulating Aspirin with a soluticn of a mixture of hydroxypropyl methylcellulose and ethylcellulose in a volatile organic solvent, ~ ~B~
drying the coated granules and compresslng the granules into sustained released tablets, which slowly release Aspirin "for a period of up to twelve hours". Gans et al. also discloses a preferred two-ply laminate tablet using two different Aspirin granulation compositions, namely: 1) said granulated Aspirin coated with the co~.bination of hydroxypropyl methylcellulose and ethylcellulose to pro-vide slow release of Aspirin over a period of up to twelve hours; and, 2) a com-position of an uncoated mixture of Aspirin and starch to p~ovide rapid release of Aspirin.
H.R. Hawthorn Australian Patent 477,515, published July 17, 1975, shows the application to Aspirin tablets of an enteric coating comprising a mixture of hydroxypropyl methylcellulose phthalate and ethyl cellulose using a solution of the coating materials in a mixture of methylene dichloride and alcohol, thereby providing a tablet with a coating of sufficient thickness to pass unchanged through the stomach.
R.E. Singiser United States Patent 3,256,111, issued June 14, 1966, shows a method of applying a protective glossy coating to previously coated and dried tablets by spray-coating hydroxypropyl methylcellulose in a non-aqueous solvent. Although Singiser appreciated the advantages of hydrcxypropyl methyl-cellulose being soluble in water as well as in organic solvents, he used only its non-aqueous solutions in his spray-coating method. The only previously coated tablets gloss-coated by Singiser are vitamin tablets.
Y. Tuji United States Patent 3,477,864, issued November 11, 1969, shows a process for coating tablets, etc., with a ~oisture-preventin~ and thermostable film, said process comprising: a~ preparing a coating composition by dissolving h~droxypropyl methylcellulose in a mixture of at least one low boiling aliphatic halide and at least one other selected low boiling organic solvent and adding to the solution one of three prescribed sealing agents; b) spraying the composition ~ ~319B
onto the tablets, etc., being rolled in a usual coating pan; c) drying the coat-ed tablets, etc.; and d) repeating the spraying and drying. The only tablets shown contain sodium chloride, sucrose, corn starch and magnesium stearate. The solvent system used to prepare the coating composition is environmentally un-desirable and the disintegration times of the coated tablets actually are greater than that of the uncoated tablets.
An article entitled "Coating tablets with water based solutions"
[Manufacturing Chemist ~ Aerosol News, p. 31J January 1976], which is based on trials by Manest~ Machines Ltd. Liverpool, England, recommends very low viscosi-ty grades ~between 6 and 15 cps) of hydroxypropyl methylcellulose, preferably with a water-soluble plasticizer, and slowly rotating pan speeds~ e.g., as low as
This invention relates to a coated acetylsalicylic acid tablet and its preparation. In particular, the invention relates to an aqueous spray-coating method of preparing an easily-swallowed, powder-free and gastric-disintegrable acetylsalicylic acid tablet and the tablet produced thereby.
Acetylsalicylic acid tablets historically have been difficult to film coat as they are friable~ dusty, and easily dissolved by water and organic solvents. Acetylsalicylic acid itself, hereinafter referred to as ASA or by its trade mark Aspirinl is readily decomposed by moisture and heat. Successful films have been applied from organic solvents using air as well as airless spray pro-ces~ing primarily because of the low flash points and rapid evaporation of the solvents involved.
S.F. Jeffries United States Patent 3,149,040, issued September 15, 1964,shows thin film coating of tablets with a particular mixture of cellulose acetate phthalate, a polyoxyethylene derivative of polypropylene glycol and plastici~er, said mixture applied in a non-aqueous system. No such coated Aspirin tablets are shown. Moreover, non-aqueous coating systems are now un-desirable from an environmental standpoint.
J.L. Anderson et al. United States Patent 3,341,416, issued September 12, 1967, discloses the encapsulation of minute particles of Aspirin in ethyl-cellulose, using a cyclohexane solu~ion of the latter. The encapsulated par-ticles are said to provide "a minimum amount of release" of Aspirin l'in the stomach" and a continuing release of Aspirin "slowly all along the extent of the intestinal tract."
E.H. Gans et al. United States Patent 3,388,041, issued June 11, 1968, teaches the preparation of a high dosage sustained release tablet containing Aspirin which comprises granulating Aspirin with a soluticn of a mixture of hydroxypropyl methylcellulose and ethylcellulose in a volatile organic solvent, ~ ~B~
drying the coated granules and compresslng the granules into sustained released tablets, which slowly release Aspirin "for a period of up to twelve hours". Gans et al. also discloses a preferred two-ply laminate tablet using two different Aspirin granulation compositions, namely: 1) said granulated Aspirin coated with the co~.bination of hydroxypropyl methylcellulose and ethylcellulose to pro-vide slow release of Aspirin over a period of up to twelve hours; and, 2) a com-position of an uncoated mixture of Aspirin and starch to p~ovide rapid release of Aspirin.
H.R. Hawthorn Australian Patent 477,515, published July 17, 1975, shows the application to Aspirin tablets of an enteric coating comprising a mixture of hydroxypropyl methylcellulose phthalate and ethyl cellulose using a solution of the coating materials in a mixture of methylene dichloride and alcohol, thereby providing a tablet with a coating of sufficient thickness to pass unchanged through the stomach.
R.E. Singiser United States Patent 3,256,111, issued June 14, 1966, shows a method of applying a protective glossy coating to previously coated and dried tablets by spray-coating hydroxypropyl methylcellulose in a non-aqueous solvent. Although Singiser appreciated the advantages of hydrcxypropyl methyl-cellulose being soluble in water as well as in organic solvents, he used only its non-aqueous solutions in his spray-coating method. The only previously coated tablets gloss-coated by Singiser are vitamin tablets.
Y. Tuji United States Patent 3,477,864, issued November 11, 1969, shows a process for coating tablets, etc., with a ~oisture-preventin~ and thermostable film, said process comprising: a~ preparing a coating composition by dissolving h~droxypropyl methylcellulose in a mixture of at least one low boiling aliphatic halide and at least one other selected low boiling organic solvent and adding to the solution one of three prescribed sealing agents; b) spraying the composition ~ ~319B
onto the tablets, etc., being rolled in a usual coating pan; c) drying the coat-ed tablets, etc.; and d) repeating the spraying and drying. The only tablets shown contain sodium chloride, sucrose, corn starch and magnesium stearate. The solvent system used to prepare the coating composition is environmentally un-desirable and the disintegration times of the coated tablets actually are greater than that of the uncoated tablets.
An article entitled "Coating tablets with water based solutions"
[Manufacturing Chemist ~ Aerosol News, p. 31J January 1976], which is based on trials by Manest~ Machines Ltd. Liverpool, England, recommends very low viscosi-ty grades ~between 6 and 15 cps) of hydroxypropyl methylcellulose, preferably with a water-soluble plasticizer, and slowly rotating pan speeds~ e.g., as low as
2 1/2 rpm. Problems of aqueous spray-coating of tablets are discussed. There is no mention of any particular pharmaceutical ingredients in the uncoated tablets.
This publication states that "the plasticisers thatcan be used is limitcd to water solubles"; however, it states that "glycerol and propylene glycol were not particularly successful". Although this publication generally states "that even water-sensitive tablets can be successfully coated without the penetration of water affecting the material", it is believed that such a general statement would not lead one skilled in the art of pharmaceutical production to applicants' process described below. It is well known that manufacturers of Aspirin and Aspirin tablets, from start to finish~ scrupulously avoid all exposure of this analgesic or its tablets to water. In fact, manufacturers of Aspirin tablets control the humidity of processing rooms to prevent decomposition of the ~.spirin and its *ablets. According~y, it is believed to be non-obvious to purposely spray an aqueous coating solution with concurrent heating OlltO uncoated Aspirin tablets as unexpectedly done successfully by applicants in their process de-scribed hereinbelow.
~ ~83~96 S. Ohno et al. United States Patent 4,017,647~ issue~ April 12, 1977, relates to a "Method for Providing Enteric Coatings on Solid Dosage Forms". Ex-ample 3 of this patent shows aqueous spray-coating of Aspirin tablets with hydroxypropyl methylcellulose phthalate, treating the coated tablets with 3N
hydrochloric acid at 20C., washing the acid-treated product with water and dry-ing the washed enteric-coated tablets. These tablets, unlike applicants' tablets discussed below, I'remained unchanged in the simulated gastric fluid and were completely disintegrated in the simulated intestinal fluid within a period of from 4 minutes and 50 seconds to 5 minutes and 30 seconds". In contrast, appli-cants' coated tablets disintegrate in simulated gastric fluid in less than one minute.
P.R. Sheth United States Patent 4,167,558, issued September 11, 1979, relates to a sustained release Aspirin tablet con~aining from about 20% by weight to about 75% by weight of one or a mixture of hydrocolloids, e.g., hydroxypropyl methylcellulose, said tablet providing, upon contact with gastric fluid, a water impe~meablc barrier on its surface and which acquires and maintains a bulk densi-ty of less than one thereby being buoyant in said fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the Aspirin contained therein is released over a prolonged period.
In a method aspect, the invention resides in the method for preparing an easily-swallowed, powder-free, gastric-disintegrable and thinly-coated ASA
tablet which does not have the characteristic ASA taste and does not produce the esophageal discomfort of an uncoated ASA tablet and which does not disintegrate in the stomach materially slower than the uncoated ASA tablet, which comprises aqueous spray-coating hydroxypropyl methylcellulose onto all exterior surfaces of an ASA tablet, the amount of hydroxypropyl methylcellulose being between 0.5 and 2.0 parts by weight per 100 parts by weight of the ASA tablet. In an embodi-~ ~3~96 ment of this method aspect, an aqueous solution of hydroxypropyl cellulose, pre-ferably containing 2% to 15% by weight of hydroxypropyl methylcellwlose and about 15% to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcellulose, is sprayed onto uncoated ASA tablets in a slowly rotating baf-fled pan in a chamber equipped to measure and control both inlet and outlet air flow ra~es and both inlet and outlet air temperatures, the inlet and outlet air rates and temperatures being sufficient to insure rapid evaporation of the water and to provide an evenly-applied thin coating of hydroxypropyl methylcellulose onto the uncoated tablets without causing their decomposition and/or physical disintegration. In a preferred embodiment of this method aspect, the pan is a 48" to 60" perforated pan through which the drying air flows and is rotated at about 2.5 to 8.0 rpm, the inlet air flow rate is maintained at about 1500 to 4000 cubic feet per minute at a temperature ranging from about 35C. to 90C. and the outlet air flow rate is maintained at about 2000 to 5000 cubic feet per minute at a temperature ranging from about 35C. to 80C. Preferably, the dew point of the inlet air is monitored and regulated at about 2C. to 15C., the air being filtered to remove dust and any other contaminants. In a particularly preferred method embodiment, a 48" perforated coating pan is used, the inlet air flow rate is maintained within the range of about 1700 to 2500 cubic feet per minute at a temperature range of about 60C. to 80C., the outlet air flow rate is maintained within the range of about 2100 to 2700 cubic feet per minute at a ~emperature range of about 50C. to 70C.. Preferably, in this embodiment, there is used a 4% to 8% by weight solution of hydroxypropyl methylcellulose in water ccntaining about 15% to 25% w/w of glyceryl triacetate as plastici~er based on the weight of hydroxypropyl methylcellulose.
In a composition aspect, the invention resides in an easily-swallowed~
powder-free and gastric-disintegrable ASA tablet thinly-coated on all of its ex-_ 5 _ ~ ~3~
terior surfaces with hydroxypropyl methylcellulose~ said coating being sufficient-ly thin as to not materially alter the gastric rate of disintegration as compared with the uncoated ASA tablet, and which coated tablet does not have the charac-teristic ASA taste and does not produce the esophageal discomfort of the un-coated ASA tablet. A preferred embodiment of this aspect of the invention is the ASA tablet unifo-rmly coated with about 0.5 to 2 parts by weight of hydroxypropyl methylcellulose per 100 parts by weight of ASA tablet and preferably also about 15 to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcel-lulose. It is preferred that the hydroxypropyl methylcellulose produces a vis-cosity between 13.0 and 18.0 centipoises when measured as a 2% by weight aqueous solution. A particularly preferred embodiment is said preferred embodiment where the hydroxypropyl methylcellulose contains not less than 28.0% and r.ot more than 30.0~ of methoxy and not less than 7.0% nor more than 12.0% of hydroxypropoxy.
The plasticizer is preferably glyceryl triacetate.
The method aspect of the invention was developed to apply a thin coat-ing of film of hydroxypropyl methylcellulose from an aqueous system to the sur-face of conventional ASA tablets for the purpose of: a) greatly improving the ease with which such tablets may be swallowed; b) greatly reducing if not eli-minating the incidence of epigastric distress; c) providing a tablet readily disintegrable in the stomach; d) eliminating the dust of packaging and handling of finished ASA tablets; and, e) impro~ing their appearance and salability.
Specific benefits provided by the method and composition aspects of the invention include: a) method covers dusty tablet surface with a slick shiny film, reducing powdery perception; b) method completely masks characteristic taste of ASA, thereby eliminating nausea and/or discomfort due to the taste of uncoated ASA
tablets; c) tablet can be easily swallowed, especially by children and elderly people who often have difficulty in swallowing tablets; d) tablet easily and ~ ~3~9~
quickly passes through mouth, throat and esophagus to the stomach without dis integration, thereby eliminating epi-gastric distress, e.g., "heart burn" and throat irritation caused by ingesting uncoated ASA tablets; e) disintegrates quickly in the stomach, thereby providing ASA for rapid entry into the blood stream.
The method aspect of the invention provides the following advantages:
a~ can be applied to ASA tablets of commercial production wi*hout special treat-ments or reformulation to increase hardness or durability to withstand breakage during film-coating manipulations; b) produces ASA tablets which resist disin-tegration in the mouth but still disintegrate in the stomach or simulated gastric fluid in less than one minute; c) does not change stability or shelf life of original tablets; d) does not slow the disintegration of the tablet in the stomach or in simulated gastric fluid test systems, i.e., USP Disintegration Test, e) is an environmentally safe process, i.e., it does not involve the use of organic solvents in the film-coating solutions, such as alcohol, methylene chloride, chlorothene, acetone, ether, and the like; f~ does not alter the dis-solution profile; g) does not result in measurable differences in salicylate blood levels compared with uncoated tablet; h) improves the appearance of the product and prevents the formation of tablet dust inside bottles of packaged goods; i) reduces difficulties encountered with high-speed automatic packaging equipment by eliminating crumbling tablets and loose powder; and, j) the trans-parent film can be applied over embossed face designs and logos without loss of fine detail.
The manner of ~aking and using the instant invention will now be generally described so as to enable a person skilled in the art of pharmaceutical development to make and use the same, as follows.
Special coating conditions are required to carry out the method aspect ~ ~31~
of the invention. Very large volumes of warm or heated air are required for the rapid evaporatiGn of moisture to prevent the chemical decomposition of the Aspirin as a result of being exposed to aqueous solutions during the coating opera~.ion. Rapid moisture evaporation is also essential to prevent the physical disintegration and destruction of the tablet during the coating procedure.
Since ASA tablets are rslatively soft, fragile~ and their surfaces and edges are easily damaged by the attrition encountered in conventional coating pans, special-ly designed pans capable of an efficient but gentle mixing action are required.
This complex action may be obtained by using large (~ 120 cm) diameter coating pans operating at unusually slow speeds of about 2.5 to 8.0 rpm, equipped with smooth baffles only slightly inclined to the direction of rotation. The tablets are thoroughly mixed with new surfaces being constantly exposed to the spray guns, but the tablets are never lifted and drcpped. Efficient mixing ac-tion is necessary to obtain a uniformly coated product when operating at such slow speeds of rotation.
The preferred hydroxypropyl methylcellulose used in the method aspect of the invention is known as hydroxypropyl methylcellulose 2910, a propylene glycol ether of methylcellulose containing not less than 28.0% and not more than 30.0% of methoxy ~-OCH3), and not less than 7.0% and not more than 12.0% of hydroxypropoxy ~-OCH2CHOHCH3), calculated on a dry basis. The preferred hydroxy-propyl methylcellulose produces a viscosity between 13.0 cps and 18.0 cps when measured as a 2% by weight aqueous solution. Other viscosities down to 3 cps are satisfactory. Acceptable coating solution compositions are especially those which range from 2% to 15% by weight of hydroxypropyl methylcellulose, preferred concentrations being between 4% and 8% by weight.
A variety of plasticizers may be advantageously employed in the coating solution, preferably at a concentration of about 15% to 25% w/w based on the ~ :~B3~9B
weight of hydroxypropyl methylcellulose. Glyceryl triacetate is the preferred plasticizer; other suitable plasticizers are glycerin, propylene glycol, dibutyl sebacate, polyethylene glycol 4,000 or 6,000, and the like.
Optionally, additional ingredients can be added to the coating solution, e.g., colorants, flavors, sweetening agents, deodorants, defoaming agents, stabil-izing agents, antioxidants, preservatives, surfactants and opacifying agents.
The aqueous film coating solutions are prepared by adding the plas-ticizer to approximately one-third the volume of purified water with rapid agita-tion; heat the mixture and add the hydroxypropyl methylcellulose with rapid agi-tation to disperse the ingredients; add the remaining two thirds volume of puri-fied water cold with agitation to dissolve. Allow the solution to stand to de-aerate. If dyes, pigments, flavorants~ deodorants~ surfactants, sweetening agents, antioxidants, preservatives or defoaming agents are desired, they may be added at this point. The aqueous coating solutions are then ready for applica-tion to the ASA tablets.
In practicing the method aspect of the invention, the following tablet-coating equipment was preferably used.
Coating Pan - ACCELA-COTA Model 48 or 60 ~Thomas Engineering, Inc., Hoffman Estates, Illinois) equipped with a 48-inch (122 cm) or 60-inch (152 cm) perforated coating pan operating at a rotational speed of about 2.5 to 8.0 rpm and providing 1500 to 4000, cu ft/min (cfm) of inlet air at a temperature ranging from about 35C. to 90C., preferably 60C. to 80C., with exhaust air measured at about 2000 to 50CO cfm, the temperature ranging from about 35C. to 80C., preferably about 50C. to 70C.
Spraying Unit - Airless Nordson Versa-Spray Circulating ~Iydraulic Pump, Model 100060, manufactured by Nordson Corporation of Amherst, Ohio, operating at 650 lbs. hydraulic pressure. Two or three automatic spray guns each fitted *
Trademark _ 9 _ ~ ~ ~3 ~ ~6 with nozzles having an orifice diameter of O.011" and a 0.009" turbulence plate are used to deliver a uniform spray pattern 2cross the tablet bed. The nozzle has an oriice of 0.011" and produces a fanned spray pattern approximately 14"
wide at a distance of 12" ~en operating under a pressure of 500 psi.
Control Unit (For the Nordson Airless Spray Unit~-Spray cycles are controlled through an automated timing panel, components of which are manufac-tured by Eagle Signal Manufacturing Division, Gulf ~ Western Industries, Inc., Davenport, IA 52803.
Spraying Unit-Air - Graco Model 953-887 Port~ble Tablst Coater Volumetric/Timed Spray Air/Airless, manufactured by Graco Inc. of Franklin Park, Illinois. Two or three automatic air spray guns Model 210744 each fitted with a 1.40 mm diameter nozzle and 1.17 mm needle to produce a fanned spray pattern of 15" wide at a distance of 8".
Control Unit (For the Graco Unit) - The air guns are controlled ~con-tinucus spray mode) via an automated air powered timing panel manufactured by Graco, Inc.
The following examples will further illustrate the invention without, however, limiting it thereto.
Example 1 1.25 kg. of hydroxypropyl methylcellulose 15 cps and 0.25 kg. of tri-acetin are rapidly agitated in 8 kg. of hot purified water. 15.5 kg. of cold purified water is added with agitation ~o dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust and spray equipment.
The resulting coating solution has the following composition:
g 8 w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin (glyceryl triacetate) 1.0 Purified Water 94-0 100. 0 Prepare uncoated Aspirin tablets, each containing 325 mg. ASA, having the appropriate logo and having the following composition.
w/w%
Starch 20 125 kg. of uncoated tablets, each weighing 405 mg., are placed in a 48" ACCELA COTA*, and are dedusted and preheated.
The film coating solution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray process.
Total application time is slightly over one hour.
A total of 4 mg. of film is applied per tablet.
Example 2 The aqueous coating solution and preparation are the same as in Example 1.
w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin 1.0 Purified Water 94.0 100.0 Prepare 125 kg. of uncoated ASA tablets, each containing 325 mg. ASA, having the appropriate logo and having the following composition:
Trademark
This publication states that "the plasticisers thatcan be used is limitcd to water solubles"; however, it states that "glycerol and propylene glycol were not particularly successful". Although this publication generally states "that even water-sensitive tablets can be successfully coated without the penetration of water affecting the material", it is believed that such a general statement would not lead one skilled in the art of pharmaceutical production to applicants' process described below. It is well known that manufacturers of Aspirin and Aspirin tablets, from start to finish~ scrupulously avoid all exposure of this analgesic or its tablets to water. In fact, manufacturers of Aspirin tablets control the humidity of processing rooms to prevent decomposition of the ~.spirin and its *ablets. According~y, it is believed to be non-obvious to purposely spray an aqueous coating solution with concurrent heating OlltO uncoated Aspirin tablets as unexpectedly done successfully by applicants in their process de-scribed hereinbelow.
~ ~83~96 S. Ohno et al. United States Patent 4,017,647~ issue~ April 12, 1977, relates to a "Method for Providing Enteric Coatings on Solid Dosage Forms". Ex-ample 3 of this patent shows aqueous spray-coating of Aspirin tablets with hydroxypropyl methylcellulose phthalate, treating the coated tablets with 3N
hydrochloric acid at 20C., washing the acid-treated product with water and dry-ing the washed enteric-coated tablets. These tablets, unlike applicants' tablets discussed below, I'remained unchanged in the simulated gastric fluid and were completely disintegrated in the simulated intestinal fluid within a period of from 4 minutes and 50 seconds to 5 minutes and 30 seconds". In contrast, appli-cants' coated tablets disintegrate in simulated gastric fluid in less than one minute.
P.R. Sheth United States Patent 4,167,558, issued September 11, 1979, relates to a sustained release Aspirin tablet con~aining from about 20% by weight to about 75% by weight of one or a mixture of hydrocolloids, e.g., hydroxypropyl methylcellulose, said tablet providing, upon contact with gastric fluid, a water impe~meablc barrier on its surface and which acquires and maintains a bulk densi-ty of less than one thereby being buoyant in said fluid and remaining buoyant in the gastric fluid of the stomach until substantially all of the Aspirin contained therein is released over a prolonged period.
In a method aspect, the invention resides in the method for preparing an easily-swallowed, powder-free, gastric-disintegrable and thinly-coated ASA
tablet which does not have the characteristic ASA taste and does not produce the esophageal discomfort of an uncoated ASA tablet and which does not disintegrate in the stomach materially slower than the uncoated ASA tablet, which comprises aqueous spray-coating hydroxypropyl methylcellulose onto all exterior surfaces of an ASA tablet, the amount of hydroxypropyl methylcellulose being between 0.5 and 2.0 parts by weight per 100 parts by weight of the ASA tablet. In an embodi-~ ~3~96 ment of this method aspect, an aqueous solution of hydroxypropyl cellulose, pre-ferably containing 2% to 15% by weight of hydroxypropyl methylcellwlose and about 15% to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcellulose, is sprayed onto uncoated ASA tablets in a slowly rotating baf-fled pan in a chamber equipped to measure and control both inlet and outlet air flow ra~es and both inlet and outlet air temperatures, the inlet and outlet air rates and temperatures being sufficient to insure rapid evaporation of the water and to provide an evenly-applied thin coating of hydroxypropyl methylcellulose onto the uncoated tablets without causing their decomposition and/or physical disintegration. In a preferred embodiment of this method aspect, the pan is a 48" to 60" perforated pan through which the drying air flows and is rotated at about 2.5 to 8.0 rpm, the inlet air flow rate is maintained at about 1500 to 4000 cubic feet per minute at a temperature ranging from about 35C. to 90C. and the outlet air flow rate is maintained at about 2000 to 5000 cubic feet per minute at a temperature ranging from about 35C. to 80C. Preferably, the dew point of the inlet air is monitored and regulated at about 2C. to 15C., the air being filtered to remove dust and any other contaminants. In a particularly preferred method embodiment, a 48" perforated coating pan is used, the inlet air flow rate is maintained within the range of about 1700 to 2500 cubic feet per minute at a temperature range of about 60C. to 80C., the outlet air flow rate is maintained within the range of about 2100 to 2700 cubic feet per minute at a ~emperature range of about 50C. to 70C.. Preferably, in this embodiment, there is used a 4% to 8% by weight solution of hydroxypropyl methylcellulose in water ccntaining about 15% to 25% w/w of glyceryl triacetate as plastici~er based on the weight of hydroxypropyl methylcellulose.
In a composition aspect, the invention resides in an easily-swallowed~
powder-free and gastric-disintegrable ASA tablet thinly-coated on all of its ex-_ 5 _ ~ ~3~
terior surfaces with hydroxypropyl methylcellulose~ said coating being sufficient-ly thin as to not materially alter the gastric rate of disintegration as compared with the uncoated ASA tablet, and which coated tablet does not have the charac-teristic ASA taste and does not produce the esophageal discomfort of the un-coated ASA tablet. A preferred embodiment of this aspect of the invention is the ASA tablet unifo-rmly coated with about 0.5 to 2 parts by weight of hydroxypropyl methylcellulose per 100 parts by weight of ASA tablet and preferably also about 15 to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcel-lulose. It is preferred that the hydroxypropyl methylcellulose produces a vis-cosity between 13.0 and 18.0 centipoises when measured as a 2% by weight aqueous solution. A particularly preferred embodiment is said preferred embodiment where the hydroxypropyl methylcellulose contains not less than 28.0% and r.ot more than 30.0~ of methoxy and not less than 7.0% nor more than 12.0% of hydroxypropoxy.
The plasticizer is preferably glyceryl triacetate.
The method aspect of the invention was developed to apply a thin coat-ing of film of hydroxypropyl methylcellulose from an aqueous system to the sur-face of conventional ASA tablets for the purpose of: a) greatly improving the ease with which such tablets may be swallowed; b) greatly reducing if not eli-minating the incidence of epigastric distress; c) providing a tablet readily disintegrable in the stomach; d) eliminating the dust of packaging and handling of finished ASA tablets; and, e) impro~ing their appearance and salability.
Specific benefits provided by the method and composition aspects of the invention include: a) method covers dusty tablet surface with a slick shiny film, reducing powdery perception; b) method completely masks characteristic taste of ASA, thereby eliminating nausea and/or discomfort due to the taste of uncoated ASA
tablets; c) tablet can be easily swallowed, especially by children and elderly people who often have difficulty in swallowing tablets; d) tablet easily and ~ ~3~9~
quickly passes through mouth, throat and esophagus to the stomach without dis integration, thereby eliminating epi-gastric distress, e.g., "heart burn" and throat irritation caused by ingesting uncoated ASA tablets; e) disintegrates quickly in the stomach, thereby providing ASA for rapid entry into the blood stream.
The method aspect of the invention provides the following advantages:
a~ can be applied to ASA tablets of commercial production wi*hout special treat-ments or reformulation to increase hardness or durability to withstand breakage during film-coating manipulations; b) produces ASA tablets which resist disin-tegration in the mouth but still disintegrate in the stomach or simulated gastric fluid in less than one minute; c) does not change stability or shelf life of original tablets; d) does not slow the disintegration of the tablet in the stomach or in simulated gastric fluid test systems, i.e., USP Disintegration Test, e) is an environmentally safe process, i.e., it does not involve the use of organic solvents in the film-coating solutions, such as alcohol, methylene chloride, chlorothene, acetone, ether, and the like; f~ does not alter the dis-solution profile; g) does not result in measurable differences in salicylate blood levels compared with uncoated tablet; h) improves the appearance of the product and prevents the formation of tablet dust inside bottles of packaged goods; i) reduces difficulties encountered with high-speed automatic packaging equipment by eliminating crumbling tablets and loose powder; and, j) the trans-parent film can be applied over embossed face designs and logos without loss of fine detail.
The manner of ~aking and using the instant invention will now be generally described so as to enable a person skilled in the art of pharmaceutical development to make and use the same, as follows.
Special coating conditions are required to carry out the method aspect ~ ~31~
of the invention. Very large volumes of warm or heated air are required for the rapid evaporatiGn of moisture to prevent the chemical decomposition of the Aspirin as a result of being exposed to aqueous solutions during the coating opera~.ion. Rapid moisture evaporation is also essential to prevent the physical disintegration and destruction of the tablet during the coating procedure.
Since ASA tablets are rslatively soft, fragile~ and their surfaces and edges are easily damaged by the attrition encountered in conventional coating pans, special-ly designed pans capable of an efficient but gentle mixing action are required.
This complex action may be obtained by using large (~ 120 cm) diameter coating pans operating at unusually slow speeds of about 2.5 to 8.0 rpm, equipped with smooth baffles only slightly inclined to the direction of rotation. The tablets are thoroughly mixed with new surfaces being constantly exposed to the spray guns, but the tablets are never lifted and drcpped. Efficient mixing ac-tion is necessary to obtain a uniformly coated product when operating at such slow speeds of rotation.
The preferred hydroxypropyl methylcellulose used in the method aspect of the invention is known as hydroxypropyl methylcellulose 2910, a propylene glycol ether of methylcellulose containing not less than 28.0% and not more than 30.0% of methoxy ~-OCH3), and not less than 7.0% and not more than 12.0% of hydroxypropoxy ~-OCH2CHOHCH3), calculated on a dry basis. The preferred hydroxy-propyl methylcellulose produces a viscosity between 13.0 cps and 18.0 cps when measured as a 2% by weight aqueous solution. Other viscosities down to 3 cps are satisfactory. Acceptable coating solution compositions are especially those which range from 2% to 15% by weight of hydroxypropyl methylcellulose, preferred concentrations being between 4% and 8% by weight.
A variety of plasticizers may be advantageously employed in the coating solution, preferably at a concentration of about 15% to 25% w/w based on the ~ :~B3~9B
weight of hydroxypropyl methylcellulose. Glyceryl triacetate is the preferred plasticizer; other suitable plasticizers are glycerin, propylene glycol, dibutyl sebacate, polyethylene glycol 4,000 or 6,000, and the like.
Optionally, additional ingredients can be added to the coating solution, e.g., colorants, flavors, sweetening agents, deodorants, defoaming agents, stabil-izing agents, antioxidants, preservatives, surfactants and opacifying agents.
The aqueous film coating solutions are prepared by adding the plas-ticizer to approximately one-third the volume of purified water with rapid agita-tion; heat the mixture and add the hydroxypropyl methylcellulose with rapid agi-tation to disperse the ingredients; add the remaining two thirds volume of puri-fied water cold with agitation to dissolve. Allow the solution to stand to de-aerate. If dyes, pigments, flavorants~ deodorants~ surfactants, sweetening agents, antioxidants, preservatives or defoaming agents are desired, they may be added at this point. The aqueous coating solutions are then ready for applica-tion to the ASA tablets.
In practicing the method aspect of the invention, the following tablet-coating equipment was preferably used.
Coating Pan - ACCELA-COTA Model 48 or 60 ~Thomas Engineering, Inc., Hoffman Estates, Illinois) equipped with a 48-inch (122 cm) or 60-inch (152 cm) perforated coating pan operating at a rotational speed of about 2.5 to 8.0 rpm and providing 1500 to 4000, cu ft/min (cfm) of inlet air at a temperature ranging from about 35C. to 90C., preferably 60C. to 80C., with exhaust air measured at about 2000 to 50CO cfm, the temperature ranging from about 35C. to 80C., preferably about 50C. to 70C.
Spraying Unit - Airless Nordson Versa-Spray Circulating ~Iydraulic Pump, Model 100060, manufactured by Nordson Corporation of Amherst, Ohio, operating at 650 lbs. hydraulic pressure. Two or three automatic spray guns each fitted *
Trademark _ 9 _ ~ ~ ~3 ~ ~6 with nozzles having an orifice diameter of O.011" and a 0.009" turbulence plate are used to deliver a uniform spray pattern 2cross the tablet bed. The nozzle has an oriice of 0.011" and produces a fanned spray pattern approximately 14"
wide at a distance of 12" ~en operating under a pressure of 500 psi.
Control Unit (For the Nordson Airless Spray Unit~-Spray cycles are controlled through an automated timing panel, components of which are manufac-tured by Eagle Signal Manufacturing Division, Gulf ~ Western Industries, Inc., Davenport, IA 52803.
Spraying Unit-Air - Graco Model 953-887 Port~ble Tablst Coater Volumetric/Timed Spray Air/Airless, manufactured by Graco Inc. of Franklin Park, Illinois. Two or three automatic air spray guns Model 210744 each fitted with a 1.40 mm diameter nozzle and 1.17 mm needle to produce a fanned spray pattern of 15" wide at a distance of 8".
Control Unit (For the Graco Unit) - The air guns are controlled ~con-tinucus spray mode) via an automated air powered timing panel manufactured by Graco, Inc.
The following examples will further illustrate the invention without, however, limiting it thereto.
Example 1 1.25 kg. of hydroxypropyl methylcellulose 15 cps and 0.25 kg. of tri-acetin are rapidly agitated in 8 kg. of hot purified water. 15.5 kg. of cold purified water is added with agitation ~o dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust and spray equipment.
The resulting coating solution has the following composition:
g 8 w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin (glyceryl triacetate) 1.0 Purified Water 94-0 100. 0 Prepare uncoated Aspirin tablets, each containing 325 mg. ASA, having the appropriate logo and having the following composition.
w/w%
Starch 20 125 kg. of uncoated tablets, each weighing 405 mg., are placed in a 48" ACCELA COTA*, and are dedusted and preheated.
The film coating solution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray process.
Total application time is slightly over one hour.
A total of 4 mg. of film is applied per tablet.
Example 2 The aqueous coating solution and preparation are the same as in Example 1.
w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin 1.0 Purified Water 94.0 100.0 Prepare 125 kg. of uncoated ASA tablets, each containing 325 mg. ASA, having the appropriate logo and having the following composition:
Trademark
3 ~ ~ ~
W/w%
Starch 20 Individual uncoated tablet weigh~ is 405 mg Place uncoated tablets in a 48" ACCELA COTA , dedust and preheat.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and 2 continuous spray process.
Total application time is slightly less than one hour (50 minutes).
A total of 4 mg. of film is applied per tablet.
Example 3 1.2 kg. of hydroxypropyl methylcellulose 15 cps and 0.24 kg. of tri-acetin are rapidly agitated in 9.56 kg. of hot purified water. 19.0 kg. of cold purified water is added with agitation to dissolution. Allow solution to de-aerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray equipment.
The resulting aqueous coating solution has the ollowing composition:
w/w%
Hydroxypropyl methylcellulose 15 cps 4.0 Triacetin 0.8 Purified Water 95.2 100.0 Prepare ASA tablets ~325 mg. ASA each) having the appropriate logo and the following composition:
w/w%
Starch 20 Trademark ~ ~331~
Individual uncoated tablet we;ght ls 405 mg. 125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating so]ution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray process.
Total application time is slightly over one hour.
A total of 4 mg. of film is applied per tablet.
_ample 4 The aqueous coating solution and preparation are the same as in Ex-ample 3.
1 0 w/w%
Hydroxypropyl methylcellulose 15 cps 4.0 Triacetin 0.8 Purified Water 95.2 100.0 Prepare ASA tablets ~325 mg. ASA each) having the appropriate logo and the following composition:
w/w%
Starch 20 Individual tablet weight uncoated is 405 mg~ 125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time is about one hour.
A total of 4 mg. of film is applied per tablet.
*
Trademark ~ ~31~B
~ le 5 1.2 kg. of hydroxypropyl methylcellulose 15 cps and 0.24 kg. of tri-acetin are rapidly agitated in 6.56 kg. of hot purified water. 12,0 kg. of cold purified wzter is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray cquipment.
The resulting solution has the following composition:
_w%
Hydroxypropyl methylcellulose 15 cps 6.0 lo Triacetin 1.2 Purified Water 92.8 100.0 Prepare uncoated ASA tablets ~500 mg. ASA each~ with the following composition:
w/w%
Starch 20 Indiviclual uncoated tablet weight is 623 mg.
125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray pro-cess.
Total application time is slightly over one hour.
A total of 6 mg. of film is applied per tablet.
Trademark ~ 1~3~
Example_6 The aqueous coating solution and preparation are the same as in Ex-ample 5.
w/w%
Hydroxypropyl methylcelluiose 15 cps 6.0 Triacetin 1.2 Purified Water 92.8 100. 0 Prepare uncoated ASA tablets (500 mg. ASA each) with the following composition:
w/w%
Starch 20 Individual uncoated tablet weight uncoated is 623 mg.
125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedustedpreheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time lS less than one hour.
- A total of 6 mg. of film is applied per tablet.
Example 7 2.5 kg. of hydroxypropyl methylcellulose 15 cps and 0.5 kg. triacetin are rapidly agltated in 16 kg. of ho~ purified water. 31 kg. o cold purified water is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan~ex-haust, and spray equipment.
*
Trademark 1 1~31~
The resul~ing aqueous coating solution has the following composition:
w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin 1.0 Purified Water 9~.0 100.0 Prepare 280 kg. of uncoated ASA tablets (325 mg. ASA each) with the following composition:
~/w%
Starch 20 Individual uncoated tablet weight is 405 mg.
280 kg. of uncoated tablets are placed in a 60'l ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applicd via a Graco Air System utilizing three automatic air spr2y guns and a continuous spray process.
Total application time is about one and one half hours.
A total of 4 mg. of film is applied per tablet.
Example 8 1.2 kg. of hydroxypropyl methylcellulose 6 cps and 0.24 kg. of tri-acetin are rapidly agitated in 4.56 kg. of hot purified water. 9 kg. of cold purified water is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray equipment.
The resulting aqueous coating solution has the following composition:
Trademark ~ ~3;~
w/w%
Hydroxypropyl methylcellulose 6 cps 8~0 Triacetin 1.6 Purified Water 90-~
100.0 Prepare uncoated ASA tablets ~325 mg. ASA each) with the following composition:
w/w%
Starch 20 Individual tablet weight uncoated is 405 mg.
125 kg. of uncoated tablets are placed in a 48" ACCELA COTA, and are dedusted and preheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time is less than forty five minutes.
A total of 4 mg. of film is applied per tablet.
The coated tablets of Examples 1 - 8 disintegrate ~USP method) in less than cne minute; their moisture levels range from 1 - 2%; and their NAS (non-ASA salicylate) content meets llSP specifications. Surprisingly, it was found that the moisture content of the coated tablets in some instances actually was less than moisture content of the uncoated tablets.
*
Trademark
W/w%
Starch 20 Individual uncoated tablet weigh~ is 405 mg Place uncoated tablets in a 48" ACCELA COTA , dedust and preheat.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and 2 continuous spray process.
Total application time is slightly less than one hour (50 minutes).
A total of 4 mg. of film is applied per tablet.
Example 3 1.2 kg. of hydroxypropyl methylcellulose 15 cps and 0.24 kg. of tri-acetin are rapidly agitated in 9.56 kg. of hot purified water. 19.0 kg. of cold purified water is added with agitation to dissolution. Allow solution to de-aerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray equipment.
The resulting aqueous coating solution has the ollowing composition:
w/w%
Hydroxypropyl methylcellulose 15 cps 4.0 Triacetin 0.8 Purified Water 95.2 100.0 Prepare ASA tablets ~325 mg. ASA each) having the appropriate logo and the following composition:
w/w%
Starch 20 Trademark ~ ~331~
Individual uncoated tablet we;ght ls 405 mg. 125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating so]ution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray process.
Total application time is slightly over one hour.
A total of 4 mg. of film is applied per tablet.
_ample 4 The aqueous coating solution and preparation are the same as in Ex-ample 3.
1 0 w/w%
Hydroxypropyl methylcellulose 15 cps 4.0 Triacetin 0.8 Purified Water 95.2 100.0 Prepare ASA tablets ~325 mg. ASA each) having the appropriate logo and the following composition:
w/w%
Starch 20 Individual tablet weight uncoated is 405 mg~ 125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time is about one hour.
A total of 4 mg. of film is applied per tablet.
*
Trademark ~ ~31~B
~ le 5 1.2 kg. of hydroxypropyl methylcellulose 15 cps and 0.24 kg. of tri-acetin are rapidly agitated in 6.56 kg. of hot purified water. 12,0 kg. of cold purified wzter is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray cquipment.
The resulting solution has the following composition:
_w%
Hydroxypropyl methylcellulose 15 cps 6.0 lo Triacetin 1.2 Purified Water 92.8 100.0 Prepare uncoated ASA tablets ~500 mg. ASA each~ with the following composition:
w/w%
Starch 20 Indiviclual uncoated tablet weight is 623 mg.
125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applied via a Nordson Airless Spray System utilizing two automatic spray guns and an intermittant spray pro-cess.
Total application time is slightly over one hour.
A total of 6 mg. of film is applied per tablet.
Trademark ~ 1~3~
Example_6 The aqueous coating solution and preparation are the same as in Ex-ample 5.
w/w%
Hydroxypropyl methylcelluiose 15 cps 6.0 Triacetin 1.2 Purified Water 92.8 100. 0 Prepare uncoated ASA tablets (500 mg. ASA each) with the following composition:
w/w%
Starch 20 Individual uncoated tablet weight uncoated is 623 mg.
125 kg. of tablets are placed in a 48" ACCELA COTA , and are dedustedpreheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time lS less than one hour.
- A total of 6 mg. of film is applied per tablet.
Example 7 2.5 kg. of hydroxypropyl methylcellulose 15 cps and 0.5 kg. triacetin are rapidly agltated in 16 kg. of ho~ purified water. 31 kg. o cold purified water is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan~ex-haust, and spray equipment.
*
Trademark 1 1~31~
The resul~ing aqueous coating solution has the following composition:
w/w%
Hydroxypropyl methylcellulose 15 cps 5.0 Triacetin 1.0 Purified Water 9~.0 100.0 Prepare 280 kg. of uncoated ASA tablets (325 mg. ASA each) with the following composition:
~/w%
Starch 20 Individual uncoated tablet weight is 405 mg.
280 kg. of uncoated tablets are placed in a 60'l ACCELA COTA , and are dedusted and preheated.
The aqueous film coating solution is applicd via a Graco Air System utilizing three automatic air spr2y guns and a continuous spray process.
Total application time is about one and one half hours.
A total of 4 mg. of film is applied per tablet.
Example 8 1.2 kg. of hydroxypropyl methylcellulose 6 cps and 0.24 kg. of tri-acetin are rapidly agitated in 4.56 kg. of hot purified water. 9 kg. of cold purified water is added with agitation to dissolve. Allow solution to deaerate before using. The solution is prepared in excess to allow for losses to the pan, exhaust, and spray equipment.
The resulting aqueous coating solution has the following composition:
Trademark ~ ~3;~
w/w%
Hydroxypropyl methylcellulose 6 cps 8~0 Triacetin 1.6 Purified Water 90-~
100.0 Prepare uncoated ASA tablets ~325 mg. ASA each) with the following composition:
w/w%
Starch 20 Individual tablet weight uncoated is 405 mg.
125 kg. of uncoated tablets are placed in a 48" ACCELA COTA, and are dedusted and preheated.
The aqueous film coating solution is applied via a Graco Air System utilizing two automatic air spray guns and a continuous spray process.
Total application time is less than forty five minutes.
A total of 4 mg. of film is applied per tablet.
The coated tablets of Examples 1 - 8 disintegrate ~USP method) in less than cne minute; their moisture levels range from 1 - 2%; and their NAS (non-ASA salicylate) content meets llSP specifications. Surprisingly, it was found that the moisture content of the coated tablets in some instances actually was less than moisture content of the uncoated tablets.
*
Trademark
Claims (21)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. The method for preparing an easily-swallowed, powder-free, gastric-disintegrable and thinly-coated acetylsalicylic acid (ASA) tablet which does not have the characteristic ASA taste and does not produce the esophageal discomfort of an uncoated ASA tablet and which does not disintegrate in the stomach materially slower than the uncoated ASA tablet, which comprises aqueous spray-coating hydroxypropyl methylcellulose onto all exterior surfaces of an ASA tablet, the amount of hydroxypropyl methylcellulose being between 0.5 and 2.0 parts by weight per 100 parts by weight of the ASA tablet.
2. The method according to claim 1 wherein said aqueous spray-coating is effected by spraying an aqueous solution of hydroxypropyl methylcellulose onto uncoated ASA tablets in a slowly rotating baffled pan in a chamber equipped to measure and control both inlet and outlet air flow rates and inlet and outlet air temperatures, the inlet and outlet air rates and temperatures being sufficient to insure rapid evaporation of the water and to provide an evenly-applied thin coating of hydroxypropyl methylcellulose onto the uncoated tablets without causing their decomposition and/or physical disintegration.
3. The method according to claim 2 where the pan is a 48 to 60 inch perforated pan through which the drying air flows and is rotated at about 2.5 to 8.0 rpm, the inlet air flow rate is maintained at about 1500 to 4000 cubic feet per minute at a temperature ranging from about 35°C. to 90°C. and the outlet air flow rate is maintained at about 2000 to 5000 cubic feet per minute at a temperature ranging from about 35°C. to 80°C.
4. The method according to claim 2 where the dew point of the inlet air is monitored and regulated to about 2°C. to 15°C. and the air is filtered to remove dust and any other contaminants.
5. The method according to claim 2 where a 48" perforated coating pan is used, the inlet air flow rate is maintained within the range of about 1700 to 2500 cubic feet per minute at a temperature range of about 60°C. to 80°C. and the outlet air flow rate is maintained within the range of about 2100 to 2700 cubic feet per minute at a temperature range of about 50°C. to 70°C.
6. The method according to claim 2 using a 2% to 15% by weight solution of hydroxypropyl methylcellulose in water.
7. The method according to claim 2 using a 4% to 8% by weight solution of hydroxypropyl methylcellulose in water.
8. The method according to claim 2 using a 2% to 15% by weight solution of hydroxypropyl methylcellulose in water containing about 15% to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcellulose.
9. The method according to claim 2 using a 4% to 8% by weight solution of hydroxypropyl methylcellulose in water containing about 15% to 25% w/w of glyceryl triacetate as plasticizer based on the weight of hydroxypropyl methyl-cellulose.
10. An easily-swallowed, powder-free and gastric-disintegrable acetyl-salicylic acid (ASA) tablet thinly-coated on all of its exterior surfaces with hydroxypropyl methylcellulose, said coating being sufficiently thin as to not materially alter the gastric rate of disintegration as compared with the un-coated ASA tablet, and which coated tablet does not have the characteristic ASA
taste and does not produce the esophageal discomfort of the uncoated ASA tablet.
taste and does not produce the esophageal discomfort of the uncoated ASA tablet.
11. The ASA tablet according to claim 10 which is uniformly coated with about 0.5 to 2 parts by weight of hydroxypropyl methylcellulose per 100 parts by weight of the ASA tablet.
12. The ASA tablet according to claim 10 or 11 where the hydroxypropyl methylcellulose contains not less than 28.0% and not more than 30.0% of methoxy and not less than 7.0% nor more than 12.0% of hydroxypropoxy.
13. The ASA tablet according to claim 10 or 11 where hydroxypropyl methylcellulose produces a viscosity between 13.0 and 18.0 centipoises when measured as a 2% by weight aqueous solution.
14. The ASA tablet according to claim 10 or 11 where the hydroxypropyl methylcellulose contains about 15 to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcellulose.
15. The ASA tablet according to claim 10 or 11 where hydroxypropyl methylcellulose contains about 15 to 25% w/w of glyceryl triacetate as plasticizer based on the weight of hydroxypropyl methylcellulose.
16. An easily-swallowed, powder-free and gastric-disintegrable acetyl-salicylic acid (ASA) tablet bearing a thin aqueous spray-coating of hydroxypropyl methylcellulose on all of its exterior surfaces, said coating being sufficiently thin as to not materially alter the gastric rate of disintegration as compared with the uncoated ASA tablet, and which coated tablet does not have the characteristic ASA taste and does not produce the esophageal discomfort of the uncoated ASA tablet.
17. The ASA tablet according to claim 16 which is uniformly coated with about 0.5 to 2 parts by weight of hydroxypropyl methylcellulose per 100 parts by weight of the ASA tablet.
18. The ASA tablet according to claim 16 or 17 where the hydroxypropyl methylcellulose contains not less than 28.0% and not more than 30.0% of methoxy and not less than 7.0% nor more than 12.0% of hydroxypropoxy.
19. The ASA tablet according to claim 16 or 17 where hydroxypropyl methylcellulose produces a viscosity between 13.0 and 18.0 centipoises when measured as a 2% by weight aqueous solution.
20. The ASA tablet according to claim 16 or 17 where the hydroxypropyl methylcellulose contains about 15 to 25% w/w of a plasticizer based on the weight of hydroxypropyl methylcellulose.
21. The ASA tablet according to claim 16 or 17 where hydroxypropyl methylcellulose contains about 15 to 25% w/w of glyceryl triacetate as plasticizer based on the weight of hydroxypropyl methylcellulose.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06174249 US4302440B1 (en) | 1980-07-31 | 1980-07-31 | Easily-swallowed, powder-free and gastric-disintegrable aspirin tablet thinly-coated with hydroxypropyl methylcellulose and aqueous spray-coating preparation thereof |
| US174,249 | 1980-07-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1163196A true CA1163196A (en) | 1984-03-06 |
Family
ID=22635437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000382866A Expired CA1163196A (en) | 1980-07-31 | 1981-07-30 | Aqueous spray-coated asa tablet |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4302440B1 (en) |
| CA (1) | CA1163196A (en) |
| MX (1) | MX6817E (en) |
| PH (1) | PH17136A (en) |
| ZA (1) | ZA815123B (en) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK151608C (en) * | 1982-08-13 | 1988-06-20 | Benzon As Alfred | PROCEDURE FOR PREPARING A PHARMACEUTICAL PERORAL POLYDEPOT PREPARATION WITH CONTROLLED RELEASE |
| US4600645A (en) * | 1985-01-31 | 1986-07-15 | Warner-Lambert Company | Process for treating dosage forms |
| GB8524001D0 (en) * | 1985-09-30 | 1985-11-06 | Glaxo Group Ltd | Pharmaceutical composition |
| US4693896A (en) * | 1985-10-07 | 1987-09-15 | Fmc Corporation | Ethylcellulose-coated, gastric-disintegrable aspirin tablet |
| US4775536A (en) * | 1986-02-24 | 1988-10-04 | Bristol-Myers Company | Enteric coated tablet and process for making |
| US4716042A (en) * | 1986-06-16 | 1987-12-29 | American Home Products Corporation | Stabilized coated aspirin tablets |
| US4802924A (en) * | 1986-06-19 | 1989-02-07 | Colorcon, Inc. | Coatings based on polydextrose for aqueous film coating of pharmaceutical food and confectionary products |
| NL193682C (en) * | 1987-05-14 | 2000-07-04 | Glaxo Group Ltd | Coated Cefuroxime Maxetil Composition. |
| ATE105474T1 (en) * | 1987-07-09 | 1994-05-15 | Wellcome Found | FLAVORED FILM-COATED TABLET. |
| US4880636A (en) * | 1988-05-13 | 1989-11-14 | Franz Robert M | Film coated tablet of ranitidine HCl |
| US4857337A (en) * | 1988-05-24 | 1989-08-15 | American Home Products Corp. (Del) | Enteric coated aspirin tablets |
| US4931286A (en) * | 1989-04-19 | 1990-06-05 | Aqualon Company | High gloss cellulose tablet coating |
| CA2011684C (en) * | 1989-07-31 | 2000-05-02 | Lawrence J. Daher | Aqueous film coating |
| US6482516B1 (en) * | 1993-07-20 | 2002-11-19 | Banner Pharmacaps, Inc. | Enrobed tablet |
| US5248516A (en) * | 1989-12-19 | 1993-09-28 | Fmc Corporation | Film-forming composition: method of producing same and use for coating pharmaceuticals and foods and the like |
| DE69121098T2 (en) * | 1990-04-04 | 1997-01-23 | Berwind Pharma Service | AQUEOUS FILM-FORMING COATING COMPOSITIONS MALTODEXTRIN AND CELLULOSE DERIVATIVES |
| EP0452862B1 (en) * | 1990-04-18 | 1995-07-19 | Asahi Kasei Kogyo Kabushiki Kaisha | Spherical seed cores, spherical granules and process for production thereof |
| JP2542122B2 (en) * | 1990-04-18 | 1996-10-09 | 旭化成工業株式会社 | Spherical nucleus, spherical granule and method for producing the same |
| CA2046089C (en) * | 1990-07-02 | 2003-12-30 | J. David Angerer | High solids low viscosity polysaccharides |
| US5098715A (en) * | 1990-12-20 | 1992-03-24 | Burroughs Wellcome Co. | Flavored film-coated tablet |
| CA2107229C (en) * | 1991-04-30 | 1997-07-22 | Thomas A. Wheatley | Taste-masked medicaments and their preparation |
| GB2256648B (en) * | 1991-05-29 | 1995-08-30 | Colorcon Ltd | Wax polish composition |
| WO1993014158A1 (en) * | 1992-01-17 | 1993-07-22 | Berwind Pharmaceutical Services, Inc. | Film coatings and film coating compositions based on cellulosic polymers and lactose |
| AU680019B2 (en) * | 1993-08-30 | 1997-07-17 | Warner-Lambert Company Llc | Tablet coating based on a melt-spun mixture of a saccharide and apolymer |
| US5702723A (en) * | 1994-08-02 | 1997-12-30 | Griffin; David | Multi-stage delivery system for ingestible medications or nutrients |
| ATE277606T1 (en) * | 1997-06-11 | 2004-10-15 | Procter & Gamble | FILM-COATED TABLET FOR IMPROVED TOLERABILITY IN THE UPPER GITTERIAL TRACT |
| US6372246B1 (en) | 1998-12-16 | 2002-04-16 | Ortho-Mcneil Pharmaceutical, Inc. | Polyethylene glycol coating for electrostatic dry deposition of pharmaceuticals |
| US6723342B1 (en) | 1999-02-08 | 2004-04-20 | Fmc Corporation | Edible coating composition |
| US6432448B1 (en) | 1999-02-08 | 2002-08-13 | Fmc Corporation | Edible coating composition |
| US20020054903A1 (en) * | 1999-10-19 | 2002-05-09 | Joseph Tyler | Direct compression polymer tablet core |
| US6733780B1 (en) | 1999-10-19 | 2004-05-11 | Genzyme Corporation | Direct compression polymer tablet core |
| US6761901B1 (en) * | 2000-05-02 | 2004-07-13 | Enzrel Inc. | Liposome drug delivery |
| MXPA01007406A (en) * | 2000-07-20 | 2003-05-19 | Du Pont Canada | High temperature and high humidity release coating for polymer film. |
| BR0115585A (en) | 2000-11-28 | 2005-12-13 | Fmc Corp | Ready-release, hardenable, edible, dry and wet coating compositions, solid dosage form and method for coating a pharmaceutical or veterinary solid dosage form, confectionery, seed, animal feed, fertilizer, pesticide tablet or food |
| US6932861B2 (en) | 2000-11-28 | 2005-08-23 | Fmc Corporation | Edible PGA coating composition |
| GB0113403D0 (en) * | 2001-06-02 | 2001-07-25 | Bioprogress Tech Int Inc | Tablet enrobing |
| AU2003210477A1 (en) * | 2002-01-09 | 2003-07-30 | Enzrel, Inc. | Liposome drug delivery of polycyclic, aromatic, antioxidant or anti-inflammatory compounds |
| TW200306866A (en) * | 2002-05-07 | 2003-12-01 | Akzo Nobel Nv | A method to improve surface properties of pharmaceutical tablets |
| AU2003237894A1 (en) * | 2002-05-20 | 2003-12-12 | Oradel Medical Ltd. | Liposome drug delivery |
| US7632521B2 (en) * | 2003-07-15 | 2009-12-15 | Eurand, Inc. | Controlled release potassium chloride tablets |
| PL2316430T3 (en) | 2004-10-08 | 2012-11-30 | Forward Pharma As | Controlled release pharmaceutical compositions comprising a fumaric acid ester |
| US20070281022A1 (en) * | 2004-10-27 | 2007-12-06 | Bunick Frank J | Dosage forms having a microreliefed surface and methods and apparatus for their production |
| US7985418B2 (en) | 2004-11-01 | 2011-07-26 | Genzyme Corporation | Aliphatic amine polymer salts for tableting |
| US20060177415A1 (en) * | 2004-11-01 | 2006-08-10 | Burke Steven K | Once a day formulation for phosphate binders |
| US20060263453A1 (en) * | 2004-11-01 | 2006-11-23 | Thomas Smith | Methods and compositions for modulating glutamate dehydrogenase |
| EP1951266A2 (en) | 2005-09-02 | 2008-08-06 | Genzyme Corporation | Method for removing phosphate and polymer used therefore |
| CN101272762B (en) | 2005-09-15 | 2013-02-06 | 基酶有限公司 | Sachet formulation for amine polymers |
| JP2010504975A (en) | 2006-09-29 | 2010-02-18 | ゲンズイメ コーポレーション | Amide dendrimer composition |
| US20100029788A1 (en) * | 2006-09-29 | 2010-02-04 | John Pelesko | Wet edible pearlescent film coatings |
| JP2010513271A (en) | 2006-12-14 | 2010-04-30 | ゲンズイメ コーポレーション | Amide-amine polymer composition |
| US20080145493A1 (en) * | 2006-12-14 | 2008-06-19 | Sensient Colors Inc. | Pearlescent pigment compositions and methods for making and using the same |
| CN102807791B (en) * | 2007-11-09 | 2014-10-15 | 联合碳化化学品及塑料技术公司 | Method for preparing very low viscosity cellulose ether and product |
| RU2552951C2 (en) | 2009-01-09 | 2015-06-10 | Форвард Фарма А/С | Pharmaceutical composition, containing one or more fumaric acid ethers in degradable matrix |
| SG174658A1 (en) | 2010-04-01 | 2011-10-28 | Theravida Inc | Pharmaceutical formulations for the treatment of overactive bladder |
| CN104603194B (en) | 2012-07-17 | 2017-11-24 | 陶氏环球技术有限责任公司 | Composition comprising organic liquid diluent and low-viscosity cellulose ether |
| KR102600541B1 (en) | 2016-01-20 | 2023-11-08 | 테라비다, 인코포레이티드 | Methods and compositions for treating hyperhidrosis |
| JP2021130618A (en) * | 2020-02-18 | 2021-09-09 | 沢井製薬株式会社 | Method for producing granule including nuclear particle, granule including nuclear particle, pharmaceutical composition that includes granule including nuclear particle, and pharmaceutical preparation including pharmaceutical composition |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3388041A (en) * | 1964-01-27 | 1968-06-11 | Richardson Merrell Inc | High dosage sustained release tablet |
| US3383236A (en) * | 1964-04-17 | 1968-05-14 | Merck & Co Inc | Continuous pharmaceutical film coating process |
| US3256111A (en) * | 1964-12-04 | 1966-06-14 | Abbott Lab | Method for coating tablets |
| US3981984A (en) * | 1968-04-01 | 1976-09-21 | Colorcon Incorporated | Color film coating of tablets and the like |
| IL43853A0 (en) * | 1973-02-16 | 1974-03-14 | Sparamedica Ag | Pharmaceutical compositions and their manufacture |
| JPS50129727A (en) * | 1974-04-04 | 1975-10-14 | ||
| US4154636A (en) * | 1975-08-27 | 1979-05-15 | Freund Industrial Co., Ltd. | Method of film-coating medicines |
| US4167558A (en) * | 1976-02-13 | 1979-09-11 | Hoffmann-La Roche Inc. | Novel sustained release tablet formulations |
| US4226849A (en) * | 1979-06-14 | 1980-10-07 | Forest Laboratories Inc. | Sustained release therapeutic compositions |
-
1980
- 1980-07-31 US US06174249 patent/US4302440B1/en not_active Expired - Lifetime
-
1981
- 1981-07-27 ZA ZA815123A patent/ZA815123B/en unknown
- 1981-07-30 MX MX819584U patent/MX6817E/en unknown
- 1981-07-30 CA CA000382866A patent/CA1163196A/en not_active Expired
- 1981-07-31 PH PH25990A patent/PH17136A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US4302440B1 (en) | 1986-08-05 |
| PH17136A (en) | 1984-06-04 |
| MX6817E (en) | 1986-08-05 |
| ZA815123B (en) | 1982-07-28 |
| US4302440A (en) | 1981-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1163196A (en) | Aqueous spray-coated asa tablet | |
| US5770225A (en) | Process of preparing a subcoated simulated capsule-like medicament | |
| US5098715A (en) | Flavored film-coated tablet | |
| CA2461275C (en) | Compositions containing sucralose | |
| US3420931A (en) | Pharmaceutical dragee | |
| CA2272237C (en) | Film coatings and film coating compositions based on dextrin | |
| JP2002515074A (en) | Moisture-proof film coating material composition, method and coated molded product | |
| JPH07103047B2 (en) | Polydextrose-based coating for aqueous film coating of pharmaceutical, food and confectionery products | |
| IE910190A1 (en) | Dual subcoated simulated capsule-like medicament | |
| US3480468A (en) | Process of preparing pharmaceutical tablet with orange-peel-like protective sugar coating | |
| EP0781549B1 (en) | A method of manufacturing a solid preparation coated with a non-solvent coating | |
| JPH0776517A (en) | Composition for medicine | |
| US20060118003A1 (en) | Light-blocking agent and film-forming composition | |
| US5683717A (en) | Gelatin coated medicament and process for making same | |
| CA1223209A (en) | Capsule shaped tablets | |
| Hemchand et al. | Recent advances in different aspects of tablet coating | |
| JP3417772B2 (en) | Solvent-free coated solid preparation and subsequent treatment method | |
| Pathak et al. | Evaluation of pentaerythritol (rosin) estergum as coating materials | |
| EP0298768A2 (en) | Flavoured film-coated tablet | |
| WO1989005634A1 (en) | A sustained-release solid medicament form and a method for the preparation therefof | |
| Kamble et al. | Enteric Coated Drug Delivery System |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |