CA1217140A - Thin film coated tablets - Google Patents
Thin film coated tabletsInfo
- Publication number
- CA1217140A CA1217140A CA000457158A CA457158A CA1217140A CA 1217140 A CA1217140 A CA 1217140A CA 000457158 A CA000457158 A CA 000457158A CA 457158 A CA457158 A CA 457158A CA 1217140 A CA1217140 A CA 1217140A
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- CA
- Canada
- Prior art keywords
- tablet
- film
- active ingredient
- pharmaceutically active
- tablet according
- 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
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Classifications
-
- 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
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- 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
-
- 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
- A61K9/2813—Inorganic compounds
-
- 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
- A61K9/282—Organic compounds, e.g. fats
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- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A film coated tablet of improved swallowability and bioavailability and containing at least one pharmaceu-tically active ingredient, said tablet being thinly coated with a film comprising as film forming agents the combination of hydroxypropyl methylcellulose; ethylcellulose and poly-vinyl pyrrolidone; said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
A film coated tablet of improved swallowability and bioavailability and containing at least one pharmaceu-tically active ingredient, said tablet being thinly coated with a film comprising as film forming agents the combination of hydroxypropyl methylcellulose; ethylcellulose and poly-vinyl pyrrolidone; said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
Description
THIN FILM COATED TABLETS
This invention relates to film coated tablets of improved swallowability. More particularly, it concerns analgesic tablets having this characteristic and also having improved absorption rates.
Perhaps the most popular unit dosage form for admini-stering pharmaceutically active ingredients is the tablet.
Although this is a widely used dosage form, nevertheless for at least some people, swallowability of such tablets presents a problem. This problem was addressed in the U.S. Patent to John et al 4,302,440 in which the patentees sought to improve the swallowability of aspirin tablets. In accordance with this patent, easily swallowed, gastric-disintegrable aspirin tablets are made by thinly coating the aspirin tablet with an aqueous solution of hydroxypropyl methylcellulose (herein-after referred to as "HPMC") which is then dried.
In investigating the character of these HPMC coated aspirin tablets, Applicants found that the HPMC film on these tablets retards the absorption of the aspirin as compared with the uncoated tablet. This is an obvious disadvantage both ~rom the point of ~iaw of the bioavail-` ability of the active ingredient in these tablets and the rate at which the aspirin gets into the bloodstream of the subject.
It has now been that the bioavailability of the active ingredients in thinly coatad tablets coated with HPMC
may be signi~icantly improved if, in addition to HPMC, there is also included in the coating polyvinyl pyrrolidone (PVP) and ethylcellulose.
.
,~
:
, .. . . .
It is accordingly an object of an aspect of the present invention to provide a readily swallowable thinly coated tablet containing a pharmaceutically active material wherein the bioavailability of said pharmaceu-tically active material is improved as compared with othersimilarly coated tablets.
It is an object of an aspect of the present invention to provide a thinly coated tablet of the aforesaid mentioned type wherein the coating material comprises a combination of HPMC, PVP and ethylcellulose.
It is an object of an aspect of the present invention to provide a process for preparing tablets of the objects of this invention mentioned.
Various aspects of the invention are as follows:
7~
-2a-A film coated tablet of improved swallowability and bioavailability and containing at least one pharmaceutically active ingredient, said tablet being thinly coated T~ith a film comprising as film forming agents the combination of hydroxy-propyl methylcellulose; ethylcellulose and polyvinyl pyrrolidone;said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
A film coated tablet of improved swallowability and bioavailability containing at least one pharmaceutically acti~e ingredient; said tablet being thinly coated with a film comprising:
(a) as film forming agents the combination of hydroxypropyl methycellulose, ethylcellulose and polyvinyl pyrrolidone;
(b) a surfactant; and (c) a carbonate salt said film coating being sufficiently thin as to be substantially 20 totally disintegrated by the gastric fluids during the t.ime that the tablet is normally in the stomach of the subject after ingestion.
This invention relates to film coated tablets of improved swallowability. More particularly, it concerns analgesic tablets having this characteristic and also having improved absorption rates.
Perhaps the most popular unit dosage form for admini-stering pharmaceutically active ingredients is the tablet.
Although this is a widely used dosage form, nevertheless for at least some people, swallowability of such tablets presents a problem. This problem was addressed in the U.S. Patent to John et al 4,302,440 in which the patentees sought to improve the swallowability of aspirin tablets. In accordance with this patent, easily swallowed, gastric-disintegrable aspirin tablets are made by thinly coating the aspirin tablet with an aqueous solution of hydroxypropyl methylcellulose (herein-after referred to as "HPMC") which is then dried.
In investigating the character of these HPMC coated aspirin tablets, Applicants found that the HPMC film on these tablets retards the absorption of the aspirin as compared with the uncoated tablet. This is an obvious disadvantage both ~rom the point of ~iaw of the bioavail-` ability of the active ingredient in these tablets and the rate at which the aspirin gets into the bloodstream of the subject.
It has now been that the bioavailability of the active ingredients in thinly coatad tablets coated with HPMC
may be signi~icantly improved if, in addition to HPMC, there is also included in the coating polyvinyl pyrrolidone (PVP) and ethylcellulose.
.
,~
:
, .. . . .
It is accordingly an object of an aspect of the present invention to provide a readily swallowable thinly coated tablet containing a pharmaceutically active material wherein the bioavailability of said pharmaceu-tically active material is improved as compared with othersimilarly coated tablets.
It is an object of an aspect of the present invention to provide a thinly coated tablet of the aforesaid mentioned type wherein the coating material comprises a combination of HPMC, PVP and ethylcellulose.
It is an object of an aspect of the present invention to provide a process for preparing tablets of the objects of this invention mentioned.
Various aspects of the invention are as follows:
7~
-2a-A film coated tablet of improved swallowability and bioavailability and containing at least one pharmaceutically active ingredient, said tablet being thinly coated T~ith a film comprising as film forming agents the combination of hydroxy-propyl methylcellulose; ethylcellulose and polyvinyl pyrrolidone;said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
A film coated tablet of improved swallowability and bioavailability containing at least one pharmaceutically acti~e ingredient; said tablet being thinly coated with a film comprising:
(a) as film forming agents the combination of hydroxypropyl methycellulose, ethylcellulose and polyvinyl pyrrolidone;
(b) a surfactant; and (c) a carbonate salt said film coating being sufficiently thin as to be substantially 20 totally disintegrated by the gastric fluids during the t.ime that the tablet is normally in the stomach of the subject after ingestion.
2~7 -2b-A coating solution usefu~ for coating tablets comprising a volatile organic sol~ent system having dissolved therein based on the total weight of said coating solution:
(a) from about 4% to about 5% of a combination of film forming agents;
(b) from about 0.5~ to about 1.0% by weight of surfactant; and (c) from about 0.5% to about 1.5% of a carbonate salt said combination of fiLm forming agents comprising hydroxy-propyl methylcellulose, ethylcellulose and polyvinyl pyrrolidone.
....... . .
_ ~ 2~
-2c-It is a feature of the tablets of the present invention that they are thinly coated and disintegrable in gastric fluids. They are intended to alleviate the esophageal dis-comfort encountered by some people in swallowing tablets but not to increase the disintegration time of the tablets in the stomach. The effort is to keep this disintegration time as close to that of the uncoated tablet. In this respect, the purposes of coating the present tablets are quite different from the purposes for which tablets are provided with an enteric coating in prior art processes and products~
In the latter cases, the coatings are intended to resist disintegration in the stomach so that the acti~e ingredients do not come into contact with the gastrointestinal mucosa until the tablet enters the intestine. With this purpose in mind, the enteric coatings will be thicker than the thin coatings contemplated by the present invention.
The present invention is applicable to tablets con-taining any of a wide variety of materials and particularly, to tablets that contain pharmaceutically active ingredients.
It has been found to be especially useful in table~s con-taining analgesics. By way of exemplifying pharmaceutically active ingredients that may be contained in the present :
tablets, the following may be mentioned: analgesics (e.g.
aspirin, acetaminophen (APAP), magnesium salicylate, salicylamide and sodium salicylate; either with or without adjuvants such as caffeine); antihistamines (e.g. chlorphen-iramine maleate and brompheniramine maleate); decongestants (e.g. pseudoephedrine HCl, and phenylpropanolamine HCl);
and antitussives (e.g. dextromet~phan HBr, and diphenhydramine HCl), etc. The above inyredients may comprise the sole pharmaceutically active agent in the tablet, or may be used in combination with other pharmaceutically active ingredients.
In addition, other tablet adjuvants may also form part of the tablets prepared in accordance with this invention.
These include such materials as alkalizing agents, bulking agents, lubricants, stabilizers, disintegrants such as corn starch; modified starch such as StaRx-1500 sold by Colorcon, Inc.; Primojel and Explotab both sold by Edward Mendell Co., Inc.; lubricants such as magnesium and zinc stearate;
stearic acid; talc; silicon fluid, dimethylpolysiloxane fluid 360 Medical Type, sold by Dow Corning CorpO;
bulking agents such as microcrystalline cellulose such as Avicel p~ 101; Avicel pH 105 both sold by FMC Corporation;
Elcema 100, 150 or 250 sold by Degussa Corp., spray dried lactose and dicalcium phosphate; stabilizers or surfactants suc~ as Tween 20~ 60 or 80 sold by Atlas Chemical Corp;
sodium lauryl sulfate; anticaking agents such as Cab-O-Sil sold by Cabot Corp., S~loid 244 FP sold by Devisen Chemical Inc., Aerosil, Supernat 50 S, both sold by De~ussa Corp.
The tablets which are to be coated according to the present invention may be prepared in any of a number of ways well known to those skilled in this art. The particular tabletting procedure employed forms no part of the invention with which we are concerned.
. ~
: `:
, As indicated above, the instant tablets are provided with a thin film of a film forming combination of HPMC, PVP and ethylcellulose. The thickness of the film is most conveniently expressed as the percent by weight of the film based on the weight of the uncoated tablet. This may vary somewhat. The only limitation is that the film is suffici-ently thin so that it will be readily disintegrable in gastric fluids. Generally, the film will be in the range of from about 0.5% to about 5.0~ by weight based on the weight of the uncoated tablet. Optimally, this will be in the range of from about 1% to about 3% on the same weight basis.
The combined quantity of HPMC, PVP and ethylcellulose that may be contained in film of the tablets of interest may also vary. Usually, this will constitute between about 0.25% to about 2.7% by weight based on the total weight of the uncoated tablet, with the preferred range being from about 0.54% to about 1.62% on the same weight basis.
The relative quantities of the individual film formers may also be present in the film over a range of concentration. Based on the total weight of the uncoated tablet, these ranges on a weight basis may be as follows:
HPMC from about 0.09% to about 0.90~; PVP from about 0.09%
to about 0.90%; ethylcellulose from about 0.09% to about o.90%.
HPMC is a propylene glycol ether of methylcelluloseO
A number of commercial HPMCs are available ~n the market that can be used in this invention. Among them, mention a~ ~
may be made of Methocel E (Dow3; Methocel F (Dow); Methocel J
(Dow); Methocel K (Dow); Viscotran MHPC (Henkel) etc. A
material of choice is marketed under the trade designation Methocel E-15 premium. This is characterized as having a viscosity of 15 cps at room temperature.
PVP employed herein is a linear polymer of l-vinyl-pyrrolidone that conforms to the general formula:
CH CH2 ~
x ~ N~ o where x is the degree of polymerization. This too is avail-able commercially under several trade names. A material that has been found to be especially useful is sold by GAF
Corporation under the trade name POVIDONE K-29-32 having a molecular weight of about 40,000.
Ethylcellulose utilized is an ethyl ether of cellulose. A suitable ethycellulose is marketed by the Dow Chemical Company under the trade designation Ethoce~ N-10.
This ~aterial has a viscosity of about 10 cps.
In certain preferred forms of this invention, it has been found ~o be advantageous to incorporate a carbonate salt in the films that are deposited on the tablets. This has an advantage in that it serves to facilitate the rupturing of the film on the coated tablet when the`latter comes in contact with the acidic gastric 1uids. In this fashion, the active ingredien~s of the tablet become available for absorption into the bloodstream more rapidly In some instances, the carbonate salt may also serve as an opacifyer for the film.
Any of several carbonate salts may be used for this purpose. By way of illustration, the following may be mentioned:
magnesium caxbonate; calcium carbonate; sodium carbona~e and sodium bicarbonate. However, magnesium carbonate has been 7~
found to be particularly suitable. The carbonate salt will ordinarily comprise about 0.06% to about 0.60~ by weight of the uncoated tablet. In a preferred form of this invention, the range will be from about 0.12% to about 0.36% on the same weight basis.
It has also been found useful to incorporate a surfact-ant in the thin film coating of the present tablets. This serves to solubilize the film and/or the active ingredients in the ~astric fluids and therefore, also acts to accelerate the absorption of the active ingredients into the bloodstream.
Many well known surfactants may be used for this purpose.
These include such materials as sodium lauryl sulfate, Tween 80, Tween 60, Tween 20, Arlacel 20 all sold by Atlas Chemical Co., and dioctylsodiumsulfosuccinate. From among this group, sodium lauryl sulfate has been found to be particularly useful. When present in the instant film coating, the surfactant will comprise from about 0.03% to about 0.30%
by weight based on the total weight of the uncoated tablet, with the preferred range being from about 0.06% to about 0.18%
on the same weight basis.
The film coate~ tablets of this in~ention are prepared by coating the tablets with a solution of HPMC, PVP and ethyl-cellulose in a volatile solvent system. A number of volatile solvents, alone or in combination with each other, may be used as the principal vehicle. These include such solvents as methylene chloride, methanol, ethyl alcohol and isopropyl alcohol. Gaod results have been obtained with a solvent system comprising a combination of methylene chloride and methanol.
The volatile solvent system will usually comprise from about 80~ to about 95% by weight based on the total weight o~ film coating solution. In a preferred aspect of this invention, it will constitute between about 85% to about 90%
g by weight on the same weight basis.
When the col~ination of methylene chloride and methanol is used as the solvent system, the major portion of the solvent system will generally be methylene chloride. For the most part, the weight ratio of methylene chloride to methanol will be in the range of from about 50:50 to about 80:20 with the preferred range being from about 60:40 to 70:30.
The combination of film forming agents (i.e HPMC, PVP
and ethylc~llulose) will constitute from about 4% to about 5%
by weight based on the film coating solution. The content of the individual film forming agents of this combination may vary with HPMC comprising from about 1% to about 3% by weight of the film coating solution, PVP comprising from about 1% to about 3% and ethylcellulose comprising about 1% to about 3% on the same weight basis.
In addition to the above ingredients, one or more sur-factants (i.e~ the surfactant component) are ad~antayeously included in the film coating solution. Usually, this will comprise from about 0.5~ to about 1.0% by weight of the film coating solution. Optimally, this range will be from about 0.6% to about 0.9% on the same weight basis As a further ingredient, it is useful to incorporate a carbonate salt in the film coating solution. This may comprise one or more carbonates. As previously indicated, magnesium carbonate is the carbonate of choice. The carbonate component will generally comprise from about 0.5%
to about 1.5~ by weight of the film coating solution with the preferred range being from about 0.9~ to about 1.1% on the same weight basis.
The tablets of ~he present in~ention may be coated with film coating solution described abo~e using any of the coating procedures well known in this art. In one typical procedure, a weighed quantity of uncoated tablets is placed in a coating pan (eOg. Accella Cote pan).
The following Examples are given to further illustrate the present invention. It is to be understood, however, that the invention is not limited thereto.
EXAMPLE l A. Coating Formulation (CE 1822-31) ~ by Wt.
Methylene chloride 60.00 Methocel 15 cps (HPMC) 1.50 Ethocel 10 cps 1.50 PVP 1.50 Methanol 30.00 Sodium lauryl sulfate 0.50 Magnesium carbonate 1.00 Propylene glycol 0.75 Mineral oil, light 0.25 Tween 80 0.25 Opaspray Yellow K-1-218~ 2.75 Methocel 15 cps, Ethocel 10 cps and PVP are first dissolved in methylene chloride. Methanol is added to the mix to complete the solution. Sodium lauryl sulfate, magnesium carbonate, propylene glycol, mineral oil light, Tween 80 and Opaspray Yellow K-1-2184 are mixed together separately to form flurry. It is then added to the polymer solution and thoroughly mixed together.
The tablet core is formed from two adjacent layers Tablet formulation 87301-68 is a typical core composition.
Percentages are based on the weight of the layer.
~ i3 Layer I:
Aspirin (80 mesh) 84.749 Corn starch 15.001 Sodium lauryl sulfate (phos. buffered) 0.250 Layer II:
Magnesium carbonate (granular) 44.955 Calcium carbonate (granular)39.960 Corn starch (10% aq. paste~4.995 Corn starch (dry powder) 9.590 Castor oil (hydrogenated, powder~ 0.500 Water, deionized QS to 100 The tablets are coated by placing a weighed amount in a coating pan sold by Thomson Engineering Co. under the name Accela-Cote pan. The temperature of the tablet bed is brought up to 40-45C. The film coating formulation such as the aforementioned coating formulation CE 1822-31, is sprayed continuously onto the tablets~while the pan is in motion.
Spraying is done by the GRECO UniYersal Spray Pump sold by Greco, Inc. The vapoxs are exhausted out of the pan through an exhaust vent.
Suf~icient film coating solution is sprayed onto the tablets to achie~e a uniform film coat and the tablet weight is increased by 3%. The coating operation is then stopped and the coated tablets are dried in the pan with hot air for about 15 minutes, jogging the pan e~ery few minutes.
A study was conducted to evaluate the effect on the rate of absorption of aspirin (as measured by the total salicylic acid blood levels) from aspirin containing tablets ~1, r coated with a coating solution containing HPMC as compared with a coating solution containing HPMC, PVP and ethylcellulose.
The respective coatings were applied to an uncoated aspirin tablet coded as Tablet No. 87301-68 and having the foregoing composition.
Using the same procedure two batches of Tablets 87301-68 were respectively coated with coating formulations CE 1637-68 according to the invention and CE 1822-31 as a control. The first one of these formulations is given in the following Table. The second one is the same composition as is given above.
TABLE I
Coating Formulation Methylene chloride 61.275 Methocel 15 cps 3.375 Methanol 31.600 Propylene glycol 0.200 Mineral oil, light 0.075 Tween 80 0~100 Opaspray Yel'ow K-1-21843.375 Tablets coated with the control coating formula CE 1637 68 (Tablet 1594-42) and tablets coated with the coating formula CE 1822-31 according to the present invention (Tablet 1822~36) were fed to subjects under standardized conditions. Plasma salicylate concentration was detexmined in blood samples taken from the subjects 10, 20 and 40 minutes after administration of the tablets. Two studies were run, one identified as BC 5-80 and BC 28-80 respectively. In each -` ~2~ f~
of these studies, uncoated aspirin tablets were used as con-trols. The results of these studies are summarized in Table II below.
TABLE II
Aspirin Bioavailability Geometric Mean Plasma Salicylate Concentration in Blood (~/ml) ,.. _ Test No. BC 5-80 Test No. BC-28-80 min min Tablet #
Uncoated aspirin5 22 47 8 29 52 Control:
Tablet #
Coating Invention:
Tablet #
Coating CE ~822-31 2 11 44 As will be apparent from Table II, film coating CE 1822-31 improved early time absorption levels of aspirin (as measured by total salicylic acid) enough to give reasonable levels at 20 minutes and levels equivalent to uncoated aspirin tablets at 40 minutes. In contrast, the tablets with film coating OE 1637-68 (containing only HPMC as the film forming agent) gave significantly lower total salicylic acid levels than .~
,. . . .
uncoated aspirin at lO, 20 and 40 minutes.
Although the invention has been described with reference to specific forms thereof, it will be understood that many changes and modifications may be made without departing from the spirit of this invention.
(a) from about 4% to about 5% of a combination of film forming agents;
(b) from about 0.5~ to about 1.0% by weight of surfactant; and (c) from about 0.5% to about 1.5% of a carbonate salt said combination of fiLm forming agents comprising hydroxy-propyl methylcellulose, ethylcellulose and polyvinyl pyrrolidone.
....... . .
_ ~ 2~
-2c-It is a feature of the tablets of the present invention that they are thinly coated and disintegrable in gastric fluids. They are intended to alleviate the esophageal dis-comfort encountered by some people in swallowing tablets but not to increase the disintegration time of the tablets in the stomach. The effort is to keep this disintegration time as close to that of the uncoated tablet. In this respect, the purposes of coating the present tablets are quite different from the purposes for which tablets are provided with an enteric coating in prior art processes and products~
In the latter cases, the coatings are intended to resist disintegration in the stomach so that the acti~e ingredients do not come into contact with the gastrointestinal mucosa until the tablet enters the intestine. With this purpose in mind, the enteric coatings will be thicker than the thin coatings contemplated by the present invention.
The present invention is applicable to tablets con-taining any of a wide variety of materials and particularly, to tablets that contain pharmaceutically active ingredients.
It has been found to be especially useful in table~s con-taining analgesics. By way of exemplifying pharmaceutically active ingredients that may be contained in the present :
tablets, the following may be mentioned: analgesics (e.g.
aspirin, acetaminophen (APAP), magnesium salicylate, salicylamide and sodium salicylate; either with or without adjuvants such as caffeine); antihistamines (e.g. chlorphen-iramine maleate and brompheniramine maleate); decongestants (e.g. pseudoephedrine HCl, and phenylpropanolamine HCl);
and antitussives (e.g. dextromet~phan HBr, and diphenhydramine HCl), etc. The above inyredients may comprise the sole pharmaceutically active agent in the tablet, or may be used in combination with other pharmaceutically active ingredients.
In addition, other tablet adjuvants may also form part of the tablets prepared in accordance with this invention.
These include such materials as alkalizing agents, bulking agents, lubricants, stabilizers, disintegrants such as corn starch; modified starch such as StaRx-1500 sold by Colorcon, Inc.; Primojel and Explotab both sold by Edward Mendell Co., Inc.; lubricants such as magnesium and zinc stearate;
stearic acid; talc; silicon fluid, dimethylpolysiloxane fluid 360 Medical Type, sold by Dow Corning CorpO;
bulking agents such as microcrystalline cellulose such as Avicel p~ 101; Avicel pH 105 both sold by FMC Corporation;
Elcema 100, 150 or 250 sold by Degussa Corp., spray dried lactose and dicalcium phosphate; stabilizers or surfactants suc~ as Tween 20~ 60 or 80 sold by Atlas Chemical Corp;
sodium lauryl sulfate; anticaking agents such as Cab-O-Sil sold by Cabot Corp., S~loid 244 FP sold by Devisen Chemical Inc., Aerosil, Supernat 50 S, both sold by De~ussa Corp.
The tablets which are to be coated according to the present invention may be prepared in any of a number of ways well known to those skilled in this art. The particular tabletting procedure employed forms no part of the invention with which we are concerned.
. ~
: `:
, As indicated above, the instant tablets are provided with a thin film of a film forming combination of HPMC, PVP and ethylcellulose. The thickness of the film is most conveniently expressed as the percent by weight of the film based on the weight of the uncoated tablet. This may vary somewhat. The only limitation is that the film is suffici-ently thin so that it will be readily disintegrable in gastric fluids. Generally, the film will be in the range of from about 0.5% to about 5.0~ by weight based on the weight of the uncoated tablet. Optimally, this will be in the range of from about 1% to about 3% on the same weight basis.
The combined quantity of HPMC, PVP and ethylcellulose that may be contained in film of the tablets of interest may also vary. Usually, this will constitute between about 0.25% to about 2.7% by weight based on the total weight of the uncoated tablet, with the preferred range being from about 0.54% to about 1.62% on the same weight basis.
The relative quantities of the individual film formers may also be present in the film over a range of concentration. Based on the total weight of the uncoated tablet, these ranges on a weight basis may be as follows:
HPMC from about 0.09% to about 0.90~; PVP from about 0.09%
to about 0.90%; ethylcellulose from about 0.09% to about o.90%.
HPMC is a propylene glycol ether of methylcelluloseO
A number of commercial HPMCs are available ~n the market that can be used in this invention. Among them, mention a~ ~
may be made of Methocel E (Dow3; Methocel F (Dow); Methocel J
(Dow); Methocel K (Dow); Viscotran MHPC (Henkel) etc. A
material of choice is marketed under the trade designation Methocel E-15 premium. This is characterized as having a viscosity of 15 cps at room temperature.
PVP employed herein is a linear polymer of l-vinyl-pyrrolidone that conforms to the general formula:
CH CH2 ~
x ~ N~ o where x is the degree of polymerization. This too is avail-able commercially under several trade names. A material that has been found to be especially useful is sold by GAF
Corporation under the trade name POVIDONE K-29-32 having a molecular weight of about 40,000.
Ethylcellulose utilized is an ethyl ether of cellulose. A suitable ethycellulose is marketed by the Dow Chemical Company under the trade designation Ethoce~ N-10.
This ~aterial has a viscosity of about 10 cps.
In certain preferred forms of this invention, it has been found ~o be advantageous to incorporate a carbonate salt in the films that are deposited on the tablets. This has an advantage in that it serves to facilitate the rupturing of the film on the coated tablet when the`latter comes in contact with the acidic gastric 1uids. In this fashion, the active ingredien~s of the tablet become available for absorption into the bloodstream more rapidly In some instances, the carbonate salt may also serve as an opacifyer for the film.
Any of several carbonate salts may be used for this purpose. By way of illustration, the following may be mentioned:
magnesium caxbonate; calcium carbonate; sodium carbona~e and sodium bicarbonate. However, magnesium carbonate has been 7~
found to be particularly suitable. The carbonate salt will ordinarily comprise about 0.06% to about 0.60~ by weight of the uncoated tablet. In a preferred form of this invention, the range will be from about 0.12% to about 0.36% on the same weight basis.
It has also been found useful to incorporate a surfact-ant in the thin film coating of the present tablets. This serves to solubilize the film and/or the active ingredients in the ~astric fluids and therefore, also acts to accelerate the absorption of the active ingredients into the bloodstream.
Many well known surfactants may be used for this purpose.
These include such materials as sodium lauryl sulfate, Tween 80, Tween 60, Tween 20, Arlacel 20 all sold by Atlas Chemical Co., and dioctylsodiumsulfosuccinate. From among this group, sodium lauryl sulfate has been found to be particularly useful. When present in the instant film coating, the surfactant will comprise from about 0.03% to about 0.30%
by weight based on the total weight of the uncoated tablet, with the preferred range being from about 0.06% to about 0.18%
on the same weight basis.
The film coate~ tablets of this in~ention are prepared by coating the tablets with a solution of HPMC, PVP and ethyl-cellulose in a volatile solvent system. A number of volatile solvents, alone or in combination with each other, may be used as the principal vehicle. These include such solvents as methylene chloride, methanol, ethyl alcohol and isopropyl alcohol. Gaod results have been obtained with a solvent system comprising a combination of methylene chloride and methanol.
The volatile solvent system will usually comprise from about 80~ to about 95% by weight based on the total weight o~ film coating solution. In a preferred aspect of this invention, it will constitute between about 85% to about 90%
g by weight on the same weight basis.
When the col~ination of methylene chloride and methanol is used as the solvent system, the major portion of the solvent system will generally be methylene chloride. For the most part, the weight ratio of methylene chloride to methanol will be in the range of from about 50:50 to about 80:20 with the preferred range being from about 60:40 to 70:30.
The combination of film forming agents (i.e HPMC, PVP
and ethylc~llulose) will constitute from about 4% to about 5%
by weight based on the film coating solution. The content of the individual film forming agents of this combination may vary with HPMC comprising from about 1% to about 3% by weight of the film coating solution, PVP comprising from about 1% to about 3% and ethylcellulose comprising about 1% to about 3% on the same weight basis.
In addition to the above ingredients, one or more sur-factants (i.e~ the surfactant component) are ad~antayeously included in the film coating solution. Usually, this will comprise from about 0.5~ to about 1.0% by weight of the film coating solution. Optimally, this range will be from about 0.6% to about 0.9% on the same weight basis As a further ingredient, it is useful to incorporate a carbonate salt in the film coating solution. This may comprise one or more carbonates. As previously indicated, magnesium carbonate is the carbonate of choice. The carbonate component will generally comprise from about 0.5%
to about 1.5~ by weight of the film coating solution with the preferred range being from about 0.9~ to about 1.1% on the same weight basis.
The tablets of ~he present in~ention may be coated with film coating solution described abo~e using any of the coating procedures well known in this art. In one typical procedure, a weighed quantity of uncoated tablets is placed in a coating pan (eOg. Accella Cote pan).
The following Examples are given to further illustrate the present invention. It is to be understood, however, that the invention is not limited thereto.
EXAMPLE l A. Coating Formulation (CE 1822-31) ~ by Wt.
Methylene chloride 60.00 Methocel 15 cps (HPMC) 1.50 Ethocel 10 cps 1.50 PVP 1.50 Methanol 30.00 Sodium lauryl sulfate 0.50 Magnesium carbonate 1.00 Propylene glycol 0.75 Mineral oil, light 0.25 Tween 80 0.25 Opaspray Yellow K-1-218~ 2.75 Methocel 15 cps, Ethocel 10 cps and PVP are first dissolved in methylene chloride. Methanol is added to the mix to complete the solution. Sodium lauryl sulfate, magnesium carbonate, propylene glycol, mineral oil light, Tween 80 and Opaspray Yellow K-1-2184 are mixed together separately to form flurry. It is then added to the polymer solution and thoroughly mixed together.
The tablet core is formed from two adjacent layers Tablet formulation 87301-68 is a typical core composition.
Percentages are based on the weight of the layer.
~ i3 Layer I:
Aspirin (80 mesh) 84.749 Corn starch 15.001 Sodium lauryl sulfate (phos. buffered) 0.250 Layer II:
Magnesium carbonate (granular) 44.955 Calcium carbonate (granular)39.960 Corn starch (10% aq. paste~4.995 Corn starch (dry powder) 9.590 Castor oil (hydrogenated, powder~ 0.500 Water, deionized QS to 100 The tablets are coated by placing a weighed amount in a coating pan sold by Thomson Engineering Co. under the name Accela-Cote pan. The temperature of the tablet bed is brought up to 40-45C. The film coating formulation such as the aforementioned coating formulation CE 1822-31, is sprayed continuously onto the tablets~while the pan is in motion.
Spraying is done by the GRECO UniYersal Spray Pump sold by Greco, Inc. The vapoxs are exhausted out of the pan through an exhaust vent.
Suf~icient film coating solution is sprayed onto the tablets to achie~e a uniform film coat and the tablet weight is increased by 3%. The coating operation is then stopped and the coated tablets are dried in the pan with hot air for about 15 minutes, jogging the pan e~ery few minutes.
A study was conducted to evaluate the effect on the rate of absorption of aspirin (as measured by the total salicylic acid blood levels) from aspirin containing tablets ~1, r coated with a coating solution containing HPMC as compared with a coating solution containing HPMC, PVP and ethylcellulose.
The respective coatings were applied to an uncoated aspirin tablet coded as Tablet No. 87301-68 and having the foregoing composition.
Using the same procedure two batches of Tablets 87301-68 were respectively coated with coating formulations CE 1637-68 according to the invention and CE 1822-31 as a control. The first one of these formulations is given in the following Table. The second one is the same composition as is given above.
TABLE I
Coating Formulation Methylene chloride 61.275 Methocel 15 cps 3.375 Methanol 31.600 Propylene glycol 0.200 Mineral oil, light 0.075 Tween 80 0~100 Opaspray Yel'ow K-1-21843.375 Tablets coated with the control coating formula CE 1637 68 (Tablet 1594-42) and tablets coated with the coating formula CE 1822-31 according to the present invention (Tablet 1822~36) were fed to subjects under standardized conditions. Plasma salicylate concentration was detexmined in blood samples taken from the subjects 10, 20 and 40 minutes after administration of the tablets. Two studies were run, one identified as BC 5-80 and BC 28-80 respectively. In each -` ~2~ f~
of these studies, uncoated aspirin tablets were used as con-trols. The results of these studies are summarized in Table II below.
TABLE II
Aspirin Bioavailability Geometric Mean Plasma Salicylate Concentration in Blood (~/ml) ,.. _ Test No. BC 5-80 Test No. BC-28-80 min min Tablet #
Uncoated aspirin5 22 47 8 29 52 Control:
Tablet #
Coating Invention:
Tablet #
Coating CE ~822-31 2 11 44 As will be apparent from Table II, film coating CE 1822-31 improved early time absorption levels of aspirin (as measured by total salicylic acid) enough to give reasonable levels at 20 minutes and levels equivalent to uncoated aspirin tablets at 40 minutes. In contrast, the tablets with film coating OE 1637-68 (containing only HPMC as the film forming agent) gave significantly lower total salicylic acid levels than .~
,. . . .
uncoated aspirin at lO, 20 and 40 minutes.
Although the invention has been described with reference to specific forms thereof, it will be understood that many changes and modifications may be made without departing from the spirit of this invention.
Claims (28)
1. A film coated tablet of improved swallowability and bioavailability and containing at least one pharmaceutically active ingredient, said tablet being thinly coated with a film comprising as film forming agents the combination of hydroxy-propyl methylcellulose; ethylcellulose and polyvinyl pyrrolidone;
said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
2. A film coated tablet according to Claim 1 in which the weight of said film coating is in the range of from about 1% to about 3% by weight based on the total weight of the uncoated tablet.
3. A film coated tablet according to Claim 2 in which the film forming agents are present in film in the following percent ranges based on the weight of the uncoated tablet:
(a) hydroxypropyl methylcellulose from about 0.09% to about 0.90%
(b) ethylcellulose from about 0.09% to about 0.90%
(c) polyvinyl pyrrolidone from about 0.09% to about 0.90%
(a) hydroxypropyl methylcellulose from about 0.09% to about 0.90%
(b) ethylcellulose from about 0.09% to about 0.90%
(c) polyvinyl pyrrolidone from about 0.09% to about 0.90%
4. A tablet according to Claim 1, 2 or 3 in which the pharmaceutically active ingredient comprises an analgesic.
5. A tablet according to Claim 1, 2 or 3 in which said pharmaceutically active ingredient comprises aspirin.
6. A tablet according to Claim 1, 2 or 3 in which said pharmaceutically active ingredient comprises acetaminophen.
7. A film coated tablet of improved swallowability and bioavailability containing at least one pharmaceutically active ingredient; said tablet being thinly coated with a film comprising:
(a) as film forming agents the combination of hydroxypropyl methycellulose, ethylcellulose and polyvinyl pyrrolidone;
(b) a surfactant; and (c) a carbonate salt said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
(a) as film forming agents the combination of hydroxypropyl methycellulose, ethylcellulose and polyvinyl pyrrolidone;
(b) a surfactant; and (c) a carbonate salt said film coating being sufficiently thin as to be substantially totally disintegrated by the gastric fluids during the time that the tablet is normally in the stomach of the subject after ingestion.
8. A film coated tablet according to Claim 7 in which the weight of said film coating is in the range of from about 1% to about 3% by weight based on the total weight of the uncoated tablet.
9. A film coated tablet according to Claim 8 in which the film forming agents are present in film in the following percent ranges based on the weight of the uncoated tablet:
(a) hydroxypropyl methylcellulose from about 0.09% to about 0.90%
(b) ethylcellulose from about 0.09% to about 0.90%
(c) polyvinyl pyrrolidone from about 0.09% to about 0.90%
(a) hydroxypropyl methylcellulose from about 0.09% to about 0.90%
(b) ethylcellulose from about 0.09% to about 0.90%
(c) polyvinyl pyrrolidone from about 0.09% to about 0.90%
10. A film coated tablet according to Claim 9 in which there is also present in said tablet the following ingredients in the percent ranges listed below based on the weight of the uncoated tablet:
(a) surfactant from about 0.03% to about 0.30%
(b) carbonate salt from about 0.06% to about 0.60%
(a) surfactant from about 0.03% to about 0.30%
(b) carbonate salt from about 0.06% to about 0.60%
11. A film coated tablet according to Claim 10 in which said surfactant is sodium lauryl sulfate.
12. A film coated tablet according to Claim 10 in which the carbonate salt is magnesium carbonate.
13. A film coated tablet according to Claim 10 in which said surfactant is sodium lauryl sulfate and said carbonate salt is magnesium carbonate.
14. A tablet according to Claim 7, 8 or 9 in which the pharmaceutically active ingredient comprises an analgesic.
15. A tablet according to Claim 7, 8 or 9 in which said pharmaceutically active ingredient comprises aspirin.
16. A tablet according to Claim 7, 8 or 9 in which said pharmaceutically active ingredient comprises acetaminophen.
17. A coating solution useful for coating tablets comprising a volatile organic solvent system having dissolved wherein based on the total weight of said coating solution:
(a) from about 4% to about 5% of a combination of film forming agents;
(b) from about 0.5% to about 1.0% by weight of surfactant; and (c) from about 0.5% to about 1.5% of a carbonate salt said combination of film forming agents comprising hydroxy-propyl methylcellulose, ethylcellulose and polyvinyl pyrrolidone.
(a) from about 4% to about 5% of a combination of film forming agents;
(b) from about 0.5% to about 1.0% by weight of surfactant; and (c) from about 0.5% to about 1.5% of a carbonate salt said combination of film forming agents comprising hydroxy-propyl methylcellulose, ethylcellulose and polyvinyl pyrrolidone.
18. A coating solution according to Claim 17 in which said surfactant is sodium lauryl sulfate.
19. A coating solution according to Claim 17 in which the carbonate salt is magnesium carbonate.
20. A coating solution according to Claim 17 in which the surfactant is sodium lauryl sulfate and the carbonate salt is magnesium carbonate.
21. A process for coating tablets which comprises depositing on the surface of said tablets a coating solution of Claim 17, 18 or 19.
22. A tablet according to claim 10, 11 or 12 in which the pharmaceutically active ingredient comprises an analgesic.
23. A tablet according to claim 13 in which the pharmaceutically active ingredient comprises an analgesic.
24. A tablet according to claim 10, 11 or 12 in which said pharmaceutically active ingredient comprises aspirin.
25. A tablet according to claim 13 in which said pharmaceutically active ingredient comprises aspirin.
26. A tablet according to claim 10, 11 or 12 in which said pharmaceutically active ingredient comprises acetaminophen.
27. A tablet according to claim 13 in which said pharmaceutically active ingredient comprises acetaminophen.
28. A process for coating tablets which comprises depositing on the surface of said tablets a coating solution of claim 20 and drying said tablets to remove said volatile organic solvent system.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50673883A | 1983-06-22 | 1983-06-22 | |
| US506,738 | 1983-06-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1217140A true CA1217140A (en) | 1987-01-27 |
Family
ID=24015821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000457158A Expired CA1217140A (en) | 1983-06-22 | 1984-06-21 | Thin film coated tablets |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1217140A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4931286A (en) * | 1989-04-19 | 1990-06-05 | Aqualon Company | High gloss cellulose tablet coating |
| US5198227A (en) * | 1990-01-22 | 1993-03-30 | Mcneil-Ppc, Inc. | Dual subcoated simulated capsule medicament |
| US5658589A (en) * | 1989-04-28 | 1997-08-19 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| WO1997039747A1 (en) * | 1996-04-23 | 1997-10-30 | F. H. Faulding & Co. Limited | Taste masked paracetamol compositions |
-
1984
- 1984-06-21 CA CA000457158A patent/CA1217140A/en not_active Expired
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4931286A (en) * | 1989-04-19 | 1990-06-05 | Aqualon Company | High gloss cellulose tablet coating |
| US5658589A (en) * | 1989-04-28 | 1997-08-19 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US5770225A (en) * | 1989-04-28 | 1998-06-23 | Mcneil-Ppc, Inc. | Process of preparing a subcoated simulated capsule-like medicament |
| US5916592A (en) * | 1989-04-28 | 1999-06-29 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US6120801A (en) * | 1989-04-28 | 2000-09-19 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US6214380B1 (en) | 1989-04-28 | 2001-04-10 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US6326026B1 (en) | 1989-04-28 | 2001-12-04 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US7087242B2 (en) | 1989-04-28 | 2006-08-08 | Mcneil-Ppc, Inc. | Subcoated simulated capsule-like medicament |
| US5198227A (en) * | 1990-01-22 | 1993-03-30 | Mcneil-Ppc, Inc. | Dual subcoated simulated capsule medicament |
| US5296233A (en) * | 1990-01-22 | 1994-03-22 | Mcneil-Ppc, Inc. | Dual subcoated simulated capsule-like medicament |
| WO1997039747A1 (en) * | 1996-04-23 | 1997-10-30 | F. H. Faulding & Co. Limited | Taste masked paracetamol compositions |
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