CA2090912A1 - Pharmaceutical coated cores - Google Patents
Pharmaceutical coated coresInfo
- Publication number
- CA2090912A1 CA2090912A1 CA002090912A CA2090912A CA2090912A1 CA 2090912 A1 CA2090912 A1 CA 2090912A1 CA 002090912 A CA002090912 A CA 002090912A CA 2090912 A CA2090912 A CA 2090912A CA 2090912 A1 CA2090912 A1 CA 2090912A1
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- CA
- Canada
- Prior art keywords
- core
- pharmaceutical
- coating
- weight
- water
- 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.)
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT
PHARMACEUTICAL COATED CORES
A finely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid is described which pharmaceutical dosage form consists of a pharmaceutical coating on a crystalline or granular core of water-soluble or water-dispersible material.
PHARMACEUTICAL COATED CORES
A finely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid is described which pharmaceutical dosage form consists of a pharmaceutical coating on a crystalline or granular core of water-soluble or water-dispersible material.
Description
`-- 2~9~9~2 AHp-9914 /Cl PH~RMACE~TICAL COATED CORES
This invention relates to solid pharmaceutical or medicament coated cores which are essentially water soluble, the coating material being applied as a liquid to the solid core such that the core is wetted and partially dissolved by the coating material, and then dried. The pharmaceutical coated cores are for oral administration dissolved in hot or cold water or other pharmaceutically acceptable liquid.
Sugar coated pharmaceuticals are old in the art, the sugar coating generally being used to mask the taste of the usually insoluble pharmaceutical core. The sugar coating, however, is usually applied to a core which has previously been coated with a sealing coat to prevent inter mixture of the pharmaceutical containing core and the sugar coat. Note, for example, Example 12 of U.S. Patent Number 4,904,477 to Ho et al.
Other patents of interest are U.S. Patent 4,946,684 to Blank et al and U.S. Patent 4,371,516 to Gregory et al described therein. These patents deal with Fast Dissolving Dosage Forms comprising an open matrix network carrying a pharmaceutical, wherein the open matrix network is comprised of a water-soluble or water-dispersable carrier material. The carrier material can be gelatin, hydrolysed dextran, dextrin or mannitol. The carrier ~5 material and the pharmaceutical, which can be chlorpheniramine maleate, are dissol~ed or dispersed in water, and the solution or admixture is freeze dried to form solid dosage forms.
Many patents exist which disclose coating of nonpareil seeds, i.e. sugar pellets, with a pharmaceutical as a first step in the preparation of a core for further processing to make ~: sustained release medicaments. Such patents include U.S. Patents 2,921,883 and 4,810,501, the first of which discloses in Example .~
, 2 ~ 2 ~HP-99l~/CL
.
This invention relates to solid pharmaceutical or medicament coated cores which are essentially water soluble, the coating material being applied as a liquid to the solid core such that the core is wetted and partially dissolved by the coating material, and then dried. The pharmaceutical coated cores are for oral administration dissolved in hot or cold water or other pharmaceutically acceptable liquid.
Sugar coated pharmaceuticals are old in the art, the sugar coating generally being used to mask the taste of the usually insoluble pharmaceutical core. The sugar coating, however, is usually applied to a core which has previously been coated with a sealing coat to prevent inter mixture of the pharmaceutical containing core and the sugar coat. Note, for example, Example 12 of U.S. Patent Number 4,904,477 to Ho et al.
Other patents of interest are U.S. Patent 4,946,684 to Blank et al and U.S. Patent 4,371,516 to Gregory et al described therein. These patents deal with Fast Dissolving Dosage Forms comprising an open matrix network carrying a pharmaceutical, wherein the open matrix network is comprised of a water-soluble or water-dispersable carrier material. The carrier material can be gelatin, hydrolysed dextran, dextrin or mannitol. The carrier ~5 material and the pharmaceutical, which can be chlorpheniramine maleate, are dissol~ed or dispersed in water, and the solution or admixture is freeze dried to form solid dosage forms.
Many patents exist which disclose coating of nonpareil seeds, i.e. sugar pellets, with a pharmaceutical as a first step in the preparation of a core for further processing to make ~: sustained release medicaments. Such patents include U.S. Patents 2,921,883 and 4,810,501, the first of which discloses in Example .~
, 2 ~ 2 ~HP-99l~/CL
.
3 the coating of nonpareil seeds in a coating pan with a coating solution, formed by dissolving chlorprophenpyridamine maleate in a 10% gelatin solution, to form drug pellets which are then - coated with a fat-cellulosic coating solution to form a delayed release medicament. Patent 4,810,501 discloses in the example the spray coating of nonpareil seeds with a coating solution formed by mixing with water kaolin, diphenhydramine hydrochloride and hydroxypropyl cellulose. The drug layered pellets were then coated with ethyl cellulose to form sustained release pellets.
The pharmaceutical dosage forms of this invention, however, are for immediate release.
U.S. Patent No. 4,177,254 discloses solid penicillin dosage forms wherein an aqueous suspension of a penicillin and a binder is sprayed onto a fluidized bed comprising sucrose. The binder can be sucrose such that the binder admixed with the insoluble penicillin forms a layer on the sucrose particles in the fluidized bed, which layer comprises particles of penicillin dispersed throughout the binder. The solid dosage forms can be reconstituted with water to form a syrup.
This invention provides a f;nely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid, the pharmaceutical dosage form consisting of a pharmaceutical coat;ng on a core wherein:
a) the core comprises about 90% to 100% by weight of a crystalline or granular water soluble or water dispersible material or mixtures thereof based on the weight of the core, said material having a particle size of 600~m-250um (30-60 U.S.) mesh and the core comprising about 90% to about 99% by weight of the pharmaceutical dosage form;
b) the pharmaceutical coating comprises about 25% to about 50% by weight of a water soluble or water dispersible material whlch may be the same or d;fferent material as the core based on the dry ` . :
A~P-99l~/Cl : -3-' weight of the coating and about 50% to about 75%
by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating compr;sing about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the core from an aqueous solution of the water soluble or water dispersible material and the water-soluble pharmaceutical containing about 50%
to 80% by weight of water by pan coating such . that the surface of the core is dissolved and intimately admixed with the coating solution thereby forming an ;ntimate bond between the core and the water-soluble pharmaceutical.
This invention is an improved solid pharmaceutical dosage form for oral administration dissolved or suspended in a liquid 25 and having a core such as sugar the surface of which has been : wetted with an aqueous base pharmaceutical coating solution and ; then dried such that the surface of the core is dissolved and ~:` intimately admixed with the coating solution thereby forming an 3 intimate bond between ~he core and the pharmaceutical upon drying. In a preferred embodiment, the sugar core consists essentially of about 90% to 100% by weight of sugar based on the ; weight of the sugar core, the sugar core comprising about 90% to about 99% by weight of the pharmaceutical dosage form. In said embodiment, the pharmaceutical coating consists essentially of about 25% to about 50% by weight of sugar based on the weight of .
- ';
2 ~ P-9g l ~/Cl the coating and about 50% to about 75% by weight of pharm~ceutical based on the weight of the dry coating, and the dry coating comprises about 1% to about 5% by weight of the pharmaceutical dosage form. In said preferred embodiment, the pharmaceutical coating is applied by pan coating to the sugar core from an aqueous solution o~ the sugar and a water-soluble pharmaceutical containing about 50% to about 80% by weight of water, preferably at least about 70% by wei~ht of water. Too much water requires a longer processing time and too little water lG inhibits formation of the intimate bond between the sugar core and the water soluble pharmaceutical upon drying.
The invention is described in relation to the practice of its preferred embodiment, i.e. wherein the core and coating solution comprise sugar. However, as explained below, other suitable materials may be utilized in the practice of the present invention. Furthermore, it should be noted that the core and the solute of the coating solution may be non-identical materials.
The pharmaceuticals or medicaments useful in the invention include, for example, nonnarcotic analgesics such as acetaminophen; antihistamines such as terfenadine, chlorpheniramine maleate, phenylephrine hydrochloride, diphenhydramine hydrochloride, bromopheniramine maleate and pheniramine maleate; nonsteroidal antiinflammatories such as ibuprofen, ketoprofen, etodolac and indomethacin; decongestants such as pseudoephedrine hydrochloride , phenylpropanolamine hydrochloride and ephedrine hydrochloride; cough suppressants such as dextromethorphan hydrobromide and guaifenesin;
bronchodilators such as epinephrine, isoproterenol hydrochloride and theophylline; and stimulants such as caffeine~
When more than one pharmaceutical is employed, they may be divided between the pan charge and the coating solution. The water-soluble pharmaceuticals are used as an ingredient of the 2 AHp - 9 9 l 4 / C l coating solution and water-insoluble or difficultly dispersible pharmaceuticals are used as an ingredient with sugar in the pan charge. The water-soluble pharmaceuticals generally include the acid addition salts, ie the inorganic and organic acid addition salts such as the hydrochlorides, the hydrobromides and the maleates. The nonnarcotic analgesics and the antiinflammatories generally have limited solubility, as do terfenadine and epinephrine. Since the coating solution is at least about 70~
water and relatively large proportions are used, pharmaceuticals such as guaifenesin and theophylline can be used since they are ` soluble to the extent required especially in warm water. At about 50Y to 60QC guaifenesin is quite soluble in such warm water and does not precipitate out at lower temperatures of about 25QC.
Accordingly, water-soluble pharmaceuticals are those that are soluble to an extent such that 12 to 20 grams of the final pharmaceutical dosage form will provide an adequate adult dosage of the water-soluble pharmaceutical.
In addition to the sugar and the pharmaceuticals, the pan charge can contain a water-soluble polymer to promote agglomeration of the sugar particles. Such polymers useful in this invention include water soluble polymers which are nontoxic and pharmacologically acceptable, particularly for oral administration~ Illustrative of such polymers are polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, block co-polymers of ethylene oxide and propylene oxide and polyethylene glycol.
Other polymers include the natural gums such as xanthan gum, karaya gum, and the like.
Similarly the coating solution can contai~ other water-soluble ingredients such as colors, flavors, binders, and thelike, in addition to the pharmaceutical.
After the coating step is completed, water insoluble agents such as anticaking agents can ~e added. These include colloidal silicon dioxide and tricalcium phosphate. Also flavoring agents such as citric acid can be added at this point.
.
., .
- . .
~ AHp-99l~/Cl The sugars which are both useful in the practice of the invention, and preferred as the core material and in the production of the coating solution, include sucrose, dextrose, glucose, fructose, lactose, and mannose. Sucrose is the preferred sugar primarily because of its availability and low cost. However, materials other than sugars are also useful.
Generally, these materials must be either crystalline or granular. Further, they must be water-soluble or water dispersible. These include cellulosic derivatives such as sodium carboxy methyl cellulose, ethyl hydroxymethyl cellulose and methyl hydroxypropyl cellulose. These also include non-caloric sugars such as sorbitol, mannitol and zylitol. Also useful are low molecular weight polyethylene glycols, such as those having molecular weights of about 1000 to about 1500. The weight ratio of sugar to pharmaceutical is about 90:10 to about 98:2 such that the amount of a single adult dose of the dosage form of the invention will be about 12 to 20 grams, an amount that can readily be mixed with or dissolved in the pharmaceutically acceptable liquid, and can be packaged in individual sachet 2G dosages.
The invention will now be further described in the following examples.
EXA~PLE 1 ` 25 ~` In the following example a finely divided solid dosage form ` was prepared having three pharmaceutical ingredients. The charge to the coating pan contained acetaminophen in addition to the sucrose and the coating solution contained pseudoephedrine HCI
and dextromethorphan HBr as well as the sucrose. The coating pan was a 60 inch Pellegrini Model T-300 and the pump for the coating solution was a Graco-Monark 5:1 airless sprayer equipped with an 0.043 cm (0.017) inch tip and with an 45.72 cm (18 inch) fan width delivering approximately 380-400 ml of coating solution per minute. The drying air inlet temperature was set at 50QC and 2 ~ 2 AHP - 9 9 1 ~ / c l -` full air flow was 59.m3 (2100 feet3) per minute and partial air flow was 31.13 (1100 feet3) per minute. The coating pan was set to rotate at 12RPM.
The ingredients used were as follows:
Pan Charge: Sucrose Cane NF (extra fine) 30-60 mesh 244 kg Hydroxypropylmethylcellulose E-5 (HPMC) 512 g Compap L (90% Acetaminophen) 9,074 g lG The sucrose comprised about 95.3~ of the pan charge and the pharmaceutically comprised about 3.2~.
Coating Pseudoephedrine, HCl 1,008 g Solution: Dextromethorphan ~Br 504 g Sucrose, Cane NF (extra fine) 30-60 mesh 1,008 g Water 7,560 g Appearance: Clear Solution ~ The sucrose comprised about 40% of the coating solids and :` the pharmaceutical comprised about 60~ of the coating solids.
The 60" Pellegrini Pan was prewarmed for 20 minutes with full air (50QC) and then charged with sucrose, Compap L and HPMC.
With the door cover '1On" and exhaust outlet "off" the batch was then tumbled for five (5) minutes at 12 RPM to insure a uniform dry blend before the start of the spraying process.
The goal of the spraying process was to apply the coating solution as fast as possible to keep the batch as wet as possible without triggering the formation of sugar lumps.
The coating cycles, all at 12 RPM, were as follows and the total process time for coating was 127.5 minutes.
~ 8pray Time Tumble Full AirPart ~ir 1 8'00" 3'00" 8'00"
2 4'00" 2'00" 9'00"
3 4'30" 2'00" 17'00"
The pharmaceutical dosage forms of this invention, however, are for immediate release.
U.S. Patent No. 4,177,254 discloses solid penicillin dosage forms wherein an aqueous suspension of a penicillin and a binder is sprayed onto a fluidized bed comprising sucrose. The binder can be sucrose such that the binder admixed with the insoluble penicillin forms a layer on the sucrose particles in the fluidized bed, which layer comprises particles of penicillin dispersed throughout the binder. The solid dosage forms can be reconstituted with water to form a syrup.
This invention provides a f;nely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid, the pharmaceutical dosage form consisting of a pharmaceutical coat;ng on a core wherein:
a) the core comprises about 90% to 100% by weight of a crystalline or granular water soluble or water dispersible material or mixtures thereof based on the weight of the core, said material having a particle size of 600~m-250um (30-60 U.S.) mesh and the core comprising about 90% to about 99% by weight of the pharmaceutical dosage form;
b) the pharmaceutical coating comprises about 25% to about 50% by weight of a water soluble or water dispersible material whlch may be the same or d;fferent material as the core based on the dry ` . :
A~P-99l~/Cl : -3-' weight of the coating and about 50% to about 75%
by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating compr;sing about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the core from an aqueous solution of the water soluble or water dispersible material and the water-soluble pharmaceutical containing about 50%
to 80% by weight of water by pan coating such . that the surface of the core is dissolved and intimately admixed with the coating solution thereby forming an ;ntimate bond between the core and the water-soluble pharmaceutical.
This invention is an improved solid pharmaceutical dosage form for oral administration dissolved or suspended in a liquid 25 and having a core such as sugar the surface of which has been : wetted with an aqueous base pharmaceutical coating solution and ; then dried such that the surface of the core is dissolved and ~:` intimately admixed with the coating solution thereby forming an 3 intimate bond between ~he core and the pharmaceutical upon drying. In a preferred embodiment, the sugar core consists essentially of about 90% to 100% by weight of sugar based on the ; weight of the sugar core, the sugar core comprising about 90% to about 99% by weight of the pharmaceutical dosage form. In said embodiment, the pharmaceutical coating consists essentially of about 25% to about 50% by weight of sugar based on the weight of .
- ';
2 ~ P-9g l ~/Cl the coating and about 50% to about 75% by weight of pharm~ceutical based on the weight of the dry coating, and the dry coating comprises about 1% to about 5% by weight of the pharmaceutical dosage form. In said preferred embodiment, the pharmaceutical coating is applied by pan coating to the sugar core from an aqueous solution o~ the sugar and a water-soluble pharmaceutical containing about 50% to about 80% by weight of water, preferably at least about 70% by wei~ht of water. Too much water requires a longer processing time and too little water lG inhibits formation of the intimate bond between the sugar core and the water soluble pharmaceutical upon drying.
The invention is described in relation to the practice of its preferred embodiment, i.e. wherein the core and coating solution comprise sugar. However, as explained below, other suitable materials may be utilized in the practice of the present invention. Furthermore, it should be noted that the core and the solute of the coating solution may be non-identical materials.
The pharmaceuticals or medicaments useful in the invention include, for example, nonnarcotic analgesics such as acetaminophen; antihistamines such as terfenadine, chlorpheniramine maleate, phenylephrine hydrochloride, diphenhydramine hydrochloride, bromopheniramine maleate and pheniramine maleate; nonsteroidal antiinflammatories such as ibuprofen, ketoprofen, etodolac and indomethacin; decongestants such as pseudoephedrine hydrochloride , phenylpropanolamine hydrochloride and ephedrine hydrochloride; cough suppressants such as dextromethorphan hydrobromide and guaifenesin;
bronchodilators such as epinephrine, isoproterenol hydrochloride and theophylline; and stimulants such as caffeine~
When more than one pharmaceutical is employed, they may be divided between the pan charge and the coating solution. The water-soluble pharmaceuticals are used as an ingredient of the 2 AHp - 9 9 l 4 / C l coating solution and water-insoluble or difficultly dispersible pharmaceuticals are used as an ingredient with sugar in the pan charge. The water-soluble pharmaceuticals generally include the acid addition salts, ie the inorganic and organic acid addition salts such as the hydrochlorides, the hydrobromides and the maleates. The nonnarcotic analgesics and the antiinflammatories generally have limited solubility, as do terfenadine and epinephrine. Since the coating solution is at least about 70~
water and relatively large proportions are used, pharmaceuticals such as guaifenesin and theophylline can be used since they are ` soluble to the extent required especially in warm water. At about 50Y to 60QC guaifenesin is quite soluble in such warm water and does not precipitate out at lower temperatures of about 25QC.
Accordingly, water-soluble pharmaceuticals are those that are soluble to an extent such that 12 to 20 grams of the final pharmaceutical dosage form will provide an adequate adult dosage of the water-soluble pharmaceutical.
In addition to the sugar and the pharmaceuticals, the pan charge can contain a water-soluble polymer to promote agglomeration of the sugar particles. Such polymers useful in this invention include water soluble polymers which are nontoxic and pharmacologically acceptable, particularly for oral administration~ Illustrative of such polymers are polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, block co-polymers of ethylene oxide and propylene oxide and polyethylene glycol.
Other polymers include the natural gums such as xanthan gum, karaya gum, and the like.
Similarly the coating solution can contai~ other water-soluble ingredients such as colors, flavors, binders, and thelike, in addition to the pharmaceutical.
After the coating step is completed, water insoluble agents such as anticaking agents can ~e added. These include colloidal silicon dioxide and tricalcium phosphate. Also flavoring agents such as citric acid can be added at this point.
.
., .
- . .
~ AHp-99l~/Cl The sugars which are both useful in the practice of the invention, and preferred as the core material and in the production of the coating solution, include sucrose, dextrose, glucose, fructose, lactose, and mannose. Sucrose is the preferred sugar primarily because of its availability and low cost. However, materials other than sugars are also useful.
Generally, these materials must be either crystalline or granular. Further, they must be water-soluble or water dispersible. These include cellulosic derivatives such as sodium carboxy methyl cellulose, ethyl hydroxymethyl cellulose and methyl hydroxypropyl cellulose. These also include non-caloric sugars such as sorbitol, mannitol and zylitol. Also useful are low molecular weight polyethylene glycols, such as those having molecular weights of about 1000 to about 1500. The weight ratio of sugar to pharmaceutical is about 90:10 to about 98:2 such that the amount of a single adult dose of the dosage form of the invention will be about 12 to 20 grams, an amount that can readily be mixed with or dissolved in the pharmaceutically acceptable liquid, and can be packaged in individual sachet 2G dosages.
The invention will now be further described in the following examples.
EXA~PLE 1 ` 25 ~` In the following example a finely divided solid dosage form ` was prepared having three pharmaceutical ingredients. The charge to the coating pan contained acetaminophen in addition to the sucrose and the coating solution contained pseudoephedrine HCI
and dextromethorphan HBr as well as the sucrose. The coating pan was a 60 inch Pellegrini Model T-300 and the pump for the coating solution was a Graco-Monark 5:1 airless sprayer equipped with an 0.043 cm (0.017) inch tip and with an 45.72 cm (18 inch) fan width delivering approximately 380-400 ml of coating solution per minute. The drying air inlet temperature was set at 50QC and 2 ~ 2 AHP - 9 9 1 ~ / c l -` full air flow was 59.m3 (2100 feet3) per minute and partial air flow was 31.13 (1100 feet3) per minute. The coating pan was set to rotate at 12RPM.
The ingredients used were as follows:
Pan Charge: Sucrose Cane NF (extra fine) 30-60 mesh 244 kg Hydroxypropylmethylcellulose E-5 (HPMC) 512 g Compap L (90% Acetaminophen) 9,074 g lG The sucrose comprised about 95.3~ of the pan charge and the pharmaceutically comprised about 3.2~.
Coating Pseudoephedrine, HCl 1,008 g Solution: Dextromethorphan ~Br 504 g Sucrose, Cane NF (extra fine) 30-60 mesh 1,008 g Water 7,560 g Appearance: Clear Solution ~ The sucrose comprised about 40% of the coating solids and :` the pharmaceutical comprised about 60~ of the coating solids.
The 60" Pellegrini Pan was prewarmed for 20 minutes with full air (50QC) and then charged with sucrose, Compap L and HPMC.
With the door cover '1On" and exhaust outlet "off" the batch was then tumbled for five (5) minutes at 12 RPM to insure a uniform dry blend before the start of the spraying process.
The goal of the spraying process was to apply the coating solution as fast as possible to keep the batch as wet as possible without triggering the formation of sugar lumps.
The coating cycles, all at 12 RPM, were as follows and the total process time for coating was 127.5 minutes.
~ 8pray Time Tumble Full AirPart ~ir 1 8'00" 3'00" 8'00"
2 4'00" 2'00" 9'00"
3 4'30" 2'00" 17'00"
4 2'30" 2'00" 7'00"
' - ~ .
- - ' .
, .
,~, . .
. .
.
2 ~ 9 ~ AHP-99l4 /Cl 2'00~' l'oo" 4'00"
6 2'00" 1'30" 13'00"
7 30'00" (40~c) 5'00" (40QC) The coated core through Cycle #7 comprised about 95.4% by weight of sucrose and about 4.1% by weight of pharmaceutical.
At the end of Cycle #7, the moisture content was 0.21%. At - this point anticaking additives were added, colloidal silicon dioxide in the amount of 128 grams and tricalcium phosphate in the amount of 38~ grams. After tumbling for an additional 5 minutes, the moisture content was 0.15%. The total yield was 250 kilograms, i.e. about 98%.
The product was sub~ected to a screen analysis, i.e. a loO
gram sample, Rotap, for 5 minutes, and is compared to a screen analysis of the sucrose raw material as follows:
~p~ Mc~ib (U~./am~ 211/850 30/600 40/425 60/251) 80/180 Pan Sucr~ O Trace 13 40 42 4 ~penmcnt 14 Mcsh (U~ 20/850 30/600 40/425 60/250 ~ Pan ` Batcb: 0 2.7 3~ 51 14 0.2 r~cc Due to agglomeration of sugar grains during the coating process, the comparison set forth above indicates a shift from the finer to the coarser end. This is a clear indication that the water from the coating solution is not only dissolving the 2 5 surface of the substrate but also causing a bond between the grains as well.
_0 In the following example a finely divided solid dosage form o~ the invention was prepared having four pharmaceutical ingredients. The charge to the coating pan contained acetaminophen in addition to the sucrose, and the coating solution contained pseudoephedrine hydrochloride, diPhenylhydramine hydrochloride and dextromethorphan . .
-~ AHP-991~ /C1 hydrochloride as well as the sucrose. The equipment was the same as that used in Example 1.
- The ingredients used were as follows, Pan Charge: Sucrose, Cane NF (30-60 U.S./600 - 250 ~m mesh) 233 kg Hydroxypropylmethyl cellulose E-5 (HPMC) 600 g Compap L (90% Acetaminophen) 13600 g The sucrose comprises about 94.3% of the pan charge and the pharmaceutical comprises about 4.9% of the pan charge.
Coating Pseudoephedrine, HC1 750 g 10 Solution: Diphenylhydramine HCl 630 g Dextromethorphan HBr 378 g D&C Yellow #10 3024 mg FD&C Yellow #6 636 mg Sucrose, Cane NF 756 g ~; Water 7560 ml The sucrose comprised about 30% of the coating solids and the pharmaceuticals comprised about 70% of the coating solids.
- Sweetener Blend: Sucrose, Cane NF 720 g Nutrasweet 730 g Blended in bag for 1 minute ~Q Flavor Blend; Sucrose, Cane NF 3360 g Natural Lemon Flavor #16774900 g Natural Honey Flavor 1200 g Blend half of sucrose with lemon flavor in bag for 1 ` minute.
Blend other half of sucrose with honey flavor in bag for 1 ~` 25 minute.
Flavor/Anticaking Citric Acid, Fine Granular 7200 g ` Blend: Tri Calcium Phosphate 288 g Colloidal Silicon Dioxide 144 g The 60" Pellegrini pan was prewarmed for 20 minutes with full air (50QC) and then charged with sucrose, Compap L and HPMC.
With the door cover "on" and exhaust outlet "off" the batch was then tumbled for five (5) minutes at 12 RPM to insure a uniform dry blend before the start of the spraying process.
' The water was heated in a 113.6 1 (30 gallon) kettle to 55Q-60QC and there were dissolved therein the dyes, all of the ~; .
.
. .
.
- .
~ 2 AHP-9914/Cl _ 10 _ .
sucrose, the diphenylhydramine hydrochloride, the dextromethorphan hydrobromide and the pseudoephedrine hydrochloride and the admixture was mixed to a clear solution.
The coating solution was held at a temperature of above 22~C
until application.
The goal of the spraying process was to apply the coating solution as fast as possible to keep the batch as wet as possible without triggering the formation of sugar lumps.
The drying air inlet temperature was set at 50QC and full lG air flow was 59.5 - 61.3 m3 (~100-2200 feet3) per minute, partial air flow was 42.5 - 44.3 m3 (1500-1600 feet3) per minute, and exhaust was 22.2 m3 (800 feet3) p~r minute.
The coating cycles, all at 13 RPM, were as follows and the total process time for coating was about 156.5 minutes.
Step No Air Partial # Spray Time Tumble FUll Air Air 1 8'00" 3'00" 12'00"
2 4'00" 2'00" 16'00"
3 4'00" 2'00" 12'00"
0 4 Sprinkle sweetener blend ~- 2'00" (Exhaust open) 3'00" 2'00" 12'00"
6 Sprinkle lemon blend 3'00" (Exhaust open) 7 2'00" 1'30" 9'30"
8 Sprinkle honey flavor blend 3'00" (Exhaust open) 9 3'00" 1'30" 17'00"
10. Sprinkle 15 kg sucrose over a period of 3 minutes with no air tumbling, exhaust open, for dusting purposes, at a pan speed of 9RPM.
11. Partial air drying for 30 minutes at 9RPM and at the end of cycle 11 the moisture content was 0.28~ but after an additional ten minutes with partial air tumbling, the moisture content was O. 09% .
" 35 `
.
2 ~ 9 ~ 2 12. The flavor/anticaking blend was added to the batch with tumbling for five minutes at 13 RPM.
13. The pan was unloaded and the batch was screened through a #10 mesh screen and no lumps were observed. The yield was 259 kg, i.e. 98%.
After about 13-14 minutes of full air during step 9, some sticking was noticed on the pan sides. This sticking was alleviated by the dusting step 10 and the problem disappeared.
The coated core through step 9 comprised about 93.6% by weight of sucrose and about 5.6% by weight of pharmaceutical.
The finished dosage form through step 11 comprised about 92.97%
by weight of sucrose and about 5.15% by weight of pharmaceutical.
, , O
` 35 ,~
. : ;
' - ~ .
- - ' .
, .
,~, . .
. .
.
2 ~ 9 ~ AHP-99l4 /Cl 2'00~' l'oo" 4'00"
6 2'00" 1'30" 13'00"
7 30'00" (40~c) 5'00" (40QC) The coated core through Cycle #7 comprised about 95.4% by weight of sucrose and about 4.1% by weight of pharmaceutical.
At the end of Cycle #7, the moisture content was 0.21%. At - this point anticaking additives were added, colloidal silicon dioxide in the amount of 128 grams and tricalcium phosphate in the amount of 38~ grams. After tumbling for an additional 5 minutes, the moisture content was 0.15%. The total yield was 250 kilograms, i.e. about 98%.
The product was sub~ected to a screen analysis, i.e. a loO
gram sample, Rotap, for 5 minutes, and is compared to a screen analysis of the sucrose raw material as follows:
~p~ Mc~ib (U~./am~ 211/850 30/600 40/425 60/251) 80/180 Pan Sucr~ O Trace 13 40 42 4 ~penmcnt 14 Mcsh (U~ 20/850 30/600 40/425 60/250 ~ Pan ` Batcb: 0 2.7 3~ 51 14 0.2 r~cc Due to agglomeration of sugar grains during the coating process, the comparison set forth above indicates a shift from the finer to the coarser end. This is a clear indication that the water from the coating solution is not only dissolving the 2 5 surface of the substrate but also causing a bond between the grains as well.
_0 In the following example a finely divided solid dosage form o~ the invention was prepared having four pharmaceutical ingredients. The charge to the coating pan contained acetaminophen in addition to the sucrose, and the coating solution contained pseudoephedrine hydrochloride, diPhenylhydramine hydrochloride and dextromethorphan . .
-~ AHP-991~ /C1 hydrochloride as well as the sucrose. The equipment was the same as that used in Example 1.
- The ingredients used were as follows, Pan Charge: Sucrose, Cane NF (30-60 U.S./600 - 250 ~m mesh) 233 kg Hydroxypropylmethyl cellulose E-5 (HPMC) 600 g Compap L (90% Acetaminophen) 13600 g The sucrose comprises about 94.3% of the pan charge and the pharmaceutical comprises about 4.9% of the pan charge.
Coating Pseudoephedrine, HC1 750 g 10 Solution: Diphenylhydramine HCl 630 g Dextromethorphan HBr 378 g D&C Yellow #10 3024 mg FD&C Yellow #6 636 mg Sucrose, Cane NF 756 g ~; Water 7560 ml The sucrose comprised about 30% of the coating solids and the pharmaceuticals comprised about 70% of the coating solids.
- Sweetener Blend: Sucrose, Cane NF 720 g Nutrasweet 730 g Blended in bag for 1 minute ~Q Flavor Blend; Sucrose, Cane NF 3360 g Natural Lemon Flavor #16774900 g Natural Honey Flavor 1200 g Blend half of sucrose with lemon flavor in bag for 1 ` minute.
Blend other half of sucrose with honey flavor in bag for 1 ~` 25 minute.
Flavor/Anticaking Citric Acid, Fine Granular 7200 g ` Blend: Tri Calcium Phosphate 288 g Colloidal Silicon Dioxide 144 g The 60" Pellegrini pan was prewarmed for 20 minutes with full air (50QC) and then charged with sucrose, Compap L and HPMC.
With the door cover "on" and exhaust outlet "off" the batch was then tumbled for five (5) minutes at 12 RPM to insure a uniform dry blend before the start of the spraying process.
' The water was heated in a 113.6 1 (30 gallon) kettle to 55Q-60QC and there were dissolved therein the dyes, all of the ~; .
.
. .
.
- .
~ 2 AHP-9914/Cl _ 10 _ .
sucrose, the diphenylhydramine hydrochloride, the dextromethorphan hydrobromide and the pseudoephedrine hydrochloride and the admixture was mixed to a clear solution.
The coating solution was held at a temperature of above 22~C
until application.
The goal of the spraying process was to apply the coating solution as fast as possible to keep the batch as wet as possible without triggering the formation of sugar lumps.
The drying air inlet temperature was set at 50QC and full lG air flow was 59.5 - 61.3 m3 (~100-2200 feet3) per minute, partial air flow was 42.5 - 44.3 m3 (1500-1600 feet3) per minute, and exhaust was 22.2 m3 (800 feet3) p~r minute.
The coating cycles, all at 13 RPM, were as follows and the total process time for coating was about 156.5 minutes.
Step No Air Partial # Spray Time Tumble FUll Air Air 1 8'00" 3'00" 12'00"
2 4'00" 2'00" 16'00"
3 4'00" 2'00" 12'00"
0 4 Sprinkle sweetener blend ~- 2'00" (Exhaust open) 3'00" 2'00" 12'00"
6 Sprinkle lemon blend 3'00" (Exhaust open) 7 2'00" 1'30" 9'30"
8 Sprinkle honey flavor blend 3'00" (Exhaust open) 9 3'00" 1'30" 17'00"
10. Sprinkle 15 kg sucrose over a period of 3 minutes with no air tumbling, exhaust open, for dusting purposes, at a pan speed of 9RPM.
11. Partial air drying for 30 minutes at 9RPM and at the end of cycle 11 the moisture content was 0.28~ but after an additional ten minutes with partial air tumbling, the moisture content was O. 09% .
" 35 `
.
2 ~ 9 ~ 2 12. The flavor/anticaking blend was added to the batch with tumbling for five minutes at 13 RPM.
13. The pan was unloaded and the batch was screened through a #10 mesh screen and no lumps were observed. The yield was 259 kg, i.e. 98%.
After about 13-14 minutes of full air during step 9, some sticking was noticed on the pan sides. This sticking was alleviated by the dusting step 10 and the problem disappeared.
The coated core through step 9 comprised about 93.6% by weight of sucrose and about 5.6% by weight of pharmaceutical.
The finished dosage form through step 11 comprised about 92.97%
by weight of sucrose and about 5.15% by weight of pharmaceutical.
, , O
` 35 ,~
. : ;
Claims (12)
1. A finely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid, the pharmaceutical dosage form consisting of a pharmaceutical coating on a core wherein:
a) the core comprises about 90% to 100% by weight of a crystalline or granular water soluble or water dispersible material or mixtures -thereof based on the weight of the core, said material having a particle size of 600µm-250µm (30-60 U.S.) mesh and the core comprising about 90% to about 99% by weight of the pharmaceutical. dosage form;
b) the pharmaceutical coating comprises about 25% to about 50% by weight of a water soluble or water dispersible material. which may be the same or different material as the core based on the dry weight of the coating and about 50% to about 75%
by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating comprising about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the core from an aqueous solution of the water soluble or water dispersible material and the water-soluble pharmaceutical containing about 50%
to 80% by weight of water by pan coating such that the surface of the core is dissolved and intimately admixed with the coating solution thereby forming an intimate bond between the core and the water-soluble pharmaceutical.
a) the core comprises about 90% to 100% by weight of a crystalline or granular water soluble or water dispersible material or mixtures -thereof based on the weight of the core, said material having a particle size of 600µm-250µm (30-60 U.S.) mesh and the core comprising about 90% to about 99% by weight of the pharmaceutical. dosage form;
b) the pharmaceutical coating comprises about 25% to about 50% by weight of a water soluble or water dispersible material. which may be the same or different material as the core based on the dry weight of the coating and about 50% to about 75%
by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating comprising about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the core from an aqueous solution of the water soluble or water dispersible material and the water-soluble pharmaceutical containing about 50%
to 80% by weight of water by pan coating such that the surface of the core is dissolved and intimately admixed with the coating solution thereby forming an intimate bond between the core and the water-soluble pharmaceutical.
2. A finely divided solid pharmaceutical dosage form as claimed in Claim 1 wherein the pharmaceutical coating contains at least one water-soluble medicament selected from the group consisting of antihistamines, decongestants, cough suppressants and bronchodilators.
3. A finely divided solid pharmaceutical dosage form as claimed in Claim 1 wherein the core additionally contains at least one medicament selected from the group consisting of nonnarcotic analgesics and nonsteroidal antiinflammatories.
4. A finely divided solid pharmaceutical dosage form as claimed in Claim 1 wherein the core material is selected from the group consisting of sugars, non-caloric sugars, cellulosic derivatives and low molecular weight polyethylene glycols, and the pharmaceutical coating having been applied to the core from an aqueous solution comprising a compound selected from the group consisting of sugars, non-caloric sugars, cellulosic derivatives and low molecular weight polyethylene glycols, and the water-soluble pharmaceutical containing at least about 70% by weight of water.
5. A finely divided solid pharmaceutical. dosage form as claimed in Claim 1 wherein the core comprises 90% to 100% by weight of sucrose.
6. A finely divided solid pharmaceutical dosage form as Claimed in Claim 1 wherein the core contains a non-narcotic analgesic.
7. A finely divided solid pharmaceutical dosage form as claimed in Claim 1 wherein the core contains acetaminophen and the pharmaceutical coating contains pseudoephedrine hydrochloride, dextromethorphan, hydrobromide and optionally dextrome-thorphan hydrobromide.
8. A finely divided solid pharmaceutical dosage form for oral administration dissolved or suspended in a pharmaceutically acceptable liquid, the pharmaceutical dosage form consisting of a pharmaceutical coating on a sugar core wherein:
a) the sugar core consists essentially of about 90%
to 100% by weight of sugar based on the weight of the sugar core, the sugar having a particle size of 600 µm - 250 µm (30-60 U.S.) mesh and the sugar core comprising about 90% to about 99% by weight of the pharmaceutical dosage form;
b) the pharmaceutical. coating consists essentially of about 25% to about 50% by weight of sugar based on the dry weight of the coating and about 50% to about 75% by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating comprising about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the sugar core from an aqueous solution of sugar and the water-soluble pharmaceutical containing about 50% to 80% by weight of water by pan coating such that the surface of the sugar core is dissolved and intimately admixed with the coating solution thereby forming an intimate bond between the sugar core and the water-soluble pharmaceutical.
a) the sugar core consists essentially of about 90%
to 100% by weight of sugar based on the weight of the sugar core, the sugar having a particle size of 600 µm - 250 µm (30-60 U.S.) mesh and the sugar core comprising about 90% to about 99% by weight of the pharmaceutical dosage form;
b) the pharmaceutical. coating consists essentially of about 25% to about 50% by weight of sugar based on the dry weight of the coating and about 50% to about 75% by weight of at least one water-soluble pharmaceutical based on the dry weight of the coating and the coating comprising about 1% to about 5% by weight of the pharmaceutical dosage form;
and c) the pharmaceutical coating having been applied to the sugar core from an aqueous solution of sugar and the water-soluble pharmaceutical containing about 50% to 80% by weight of water by pan coating such that the surface of the sugar core is dissolved and intimately admixed with the coating solution thereby forming an intimate bond between the sugar core and the water-soluble pharmaceutical.
9. A finely divided solid pharmaceutical dosage form as claimed in Claim 8 wherein the pharmaceutical coating contains at least one water-soluble medicament selected from the group consisting of antihistamines, decongestants, cough suppressants and bronchodilators.
10. A finely divided solid pharmaceutical dosage form as claimed in Claim 8 wherein the core additionally contains at least one medicament selected from the group consisting of nonnarcotic analgesics and nonsteroidal antiinflammatories.
11. A finely divided solid pharmaceutical dosage form as claimed in Claim 8 wherein the core contains a non-narcotic analgesic.
12. A finely divided solid pharmaceutical dosage form as claimed in Claim 8 wherein the core contains acetaminophen and the pharmaceutical coating contains pseudoephedrine hydrochloride, dextromethorphan hydrobromide and optionally dextromethophan hydrobromide.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84715192A | 1992-03-05 | 1992-03-05 | |
| US847,151 | 1992-03-05 | ||
| US857293A | 1993-02-09 | 1993-02-09 | |
| US008,572 | 1993-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2090912A1 true CA2090912A1 (en) | 1993-09-06 |
Family
ID=26678331
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002090912A Abandoned CA2090912A1 (en) | 1992-03-05 | 1993-03-03 | Pharmaceutical coated cores |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0559463A1 (en) |
| JP (1) | JPH069376A (en) |
| AU (1) | AU670567B2 (en) |
| CA (1) | CA2090912A1 (en) |
| MX (1) | MX9301189A (en) |
| UY (1) | UY23551A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19856149C1 (en) * | 1998-12-04 | 2000-06-15 | Basf Ag | Process for the production of agglomerates with a core-shell structure |
| BR0009557A (en) | 1999-04-06 | 2002-05-28 | Ethypharm Lab Prod Ethiques | Pharmaceutical suspension for ibuprofen drinking |
| FR2791889B1 (en) * | 2000-04-05 | 2005-09-16 | Ethypharm Lab Prod Ethiques | IBUPROFEN ORAL PHARMACEUTICAL SUSPENSION |
| FR2881049B1 (en) * | 2005-01-24 | 2008-12-26 | Vetoquinol Sa Sa | MEDICAMENT FOR ORAL ADMINISTRATION COMPRISING A CYCLO-OXYGENASE-2 INHIBITOR, AND PROCESS FOR PREPARING THE SAME |
| US8940796B2 (en) | 2006-02-21 | 2015-01-27 | Wyeth Llc | Phenylephrine liquid formulations |
| US9005652B2 (en) | 2006-07-25 | 2015-04-14 | Wyeth | Chewable tablet containing phenylephrine |
| BR112020020941A2 (en) * | 2018-04-16 | 2021-03-02 | Bristol-Myers Squibb Company | apixaban formulations |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3446891A (en) * | 1966-05-16 | 1969-05-27 | Hoffmann La Roche | Encapsulated acacia syrup adhesive overlaid n-acetyl-p-aminophenol beadlet cores retaining thereon dextromethorphan,chlorpheniramine,and phenylephrine |
| AT336190B (en) * | 1974-07-23 | 1977-04-25 | Hurka Wilhelm | METHOD FOR MANUFACTURING MICROPELLETS FOR THE TREATMENT OF DISEASES OF THE MOUTH AND THROAT |
| GB1561301A (en) * | 1976-01-02 | 1980-02-20 | Beecham Group Ltd | Orally administrable pharmaceutical composition |
| JPS6327424A (en) * | 1986-07-17 | 1988-02-05 | Shionogi & Co Ltd | Sustained release pharmaceutical and production thereof |
| US5084287A (en) * | 1990-03-15 | 1992-01-28 | Warner-Lambert Company | Pharmaceutically useful micropellets with a drug-coated core and controlled-release polymeric coat |
-
1993
- 1993-03-02 AU AU33890/93A patent/AU670567B2/en not_active Ceased
- 1993-03-03 CA CA002090912A patent/CA2090912A1/en not_active Abandoned
- 1993-03-03 MX MX9301189A patent/MX9301189A/en not_active IP Right Cessation
- 1993-03-03 JP JP5042582A patent/JPH069376A/en active Pending
- 1993-03-04 EP EP19930301642 patent/EP0559463A1/en not_active Withdrawn
- 1993-03-04 UY UY23551A patent/UY23551A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU670567B2 (en) | 1996-07-25 |
| UY23551A1 (en) | 1993-09-01 |
| JPH069376A (en) | 1994-01-18 |
| AU3389093A (en) | 1993-09-09 |
| EP0559463A1 (en) | 1993-09-08 |
| MX9301189A (en) | 1994-07-29 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Dead |