CA1110972A - Tableting of microcapsules - Google Patents
Tableting of microcapsulesInfo
- Publication number
- CA1110972A CA1110972A CA300,184A CA300184A CA1110972A CA 1110972 A CA1110972 A CA 1110972A CA 300184 A CA300184 A CA 300184A CA 1110972 A CA1110972 A CA 1110972A
- Authority
- CA
- Canada
- Prior art keywords
- substance
- tablet
- microencapsulated
- tablets
- waxy
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Preparation (AREA)
- General Preparation And Processing Of Foods (AREA)
Abstract
Abstract of the disclosure :
A tablet or other solid shaped article produced by compression which comprises a microencapsulated substance or a substance that is itself brittle or has a brittle coating and more than 2 % w/w, of a water-soluble, natural or synthetic waxy sub? ?ance having a melting point of at least 30°C and a process for preparing the tablet or article.
A tablet or other solid shaped article produced by compression which comprises a microencapsulated substance or a substance that is itself brittle or has a brittle coating and more than 2 % w/w, of a water-soluble, natural or synthetic waxy sub? ?ance having a melting point of at least 30°C and a process for preparing the tablet or article.
Description
This invention relates to the tableting o~ brittle micro-capsules and other particles that are brittle and/or have a brittle coat.
Microcapsules have many applications as the micro-encapsulated substance is protected from external influences and vice versa, for example, stability is increased and chances of undesirable reactions with other components in a mixture are substantially eliminated, unpleasant tastes and smells can be masked, and possi-bilities of irritation hy noxious substances reduced. Micro-encapsulated substances are generally in the form of a flowable powder which in desirable for many purposes.
For other applications, for example, in pharmaceutical use, it is advantageous to provide a substance in unit form to assist correct dosing. Although it is possible to provide a unit dose comprising granules or a powder in a sachet, this form of prepara-tion is not entirely satisfactory, and the most common conventional unit dose forms of solid pharmaceutical preparations are tablets of all kinds, with pills, cachets, hard and soft gelatin capsules being less common for technical and commercial reasons. Other forms of preparations such as troches and wafers are rare nowadays.
Unit doses containing a known amount of a substance are also useful in any situation where it is desired to produce a solution of known strength.
Attempts have been made to produce unit dose preparations comprising microcapsules. Gelatin capsules containing microcapsules have been prepared, but these are not suitable for pharmaceutical use when active substances are used in high doses because the capsules containing a suitable unit dose are too large to swallow. Attempts
Microcapsules have many applications as the micro-encapsulated substance is protected from external influences and vice versa, for example, stability is increased and chances of undesirable reactions with other components in a mixture are substantially eliminated, unpleasant tastes and smells can be masked, and possi-bilities of irritation hy noxious substances reduced. Micro-encapsulated substances are generally in the form of a flowable powder which in desirable for many purposes.
For other applications, for example, in pharmaceutical use, it is advantageous to provide a substance in unit form to assist correct dosing. Although it is possible to provide a unit dose comprising granules or a powder in a sachet, this form of prepara-tion is not entirely satisfactory, and the most common conventional unit dose forms of solid pharmaceutical preparations are tablets of all kinds, with pills, cachets, hard and soft gelatin capsules being less common for technical and commercial reasons. Other forms of preparations such as troches and wafers are rare nowadays.
Unit doses containing a known amount of a substance are also useful in any situation where it is desired to produce a solution of known strength.
Attempts have been made to produce unit dose preparations comprising microcapsules. Gelatin capsules containing microcapsules have been prepared, but these are not suitable for pharmaceutical use when active substances are used in high doses because the capsules containing a suitable unit dose are too large to swallow. Attempts
-2-?
have been made to produce tablets comprising microcapsules, but -2a-~ 72 ~ OR 77/F 272 again the problem is size: most microcapsules are very brittle so large amounts of carriers for example, mixtures of lactose, microcrystalline cellulose and starch, have been found to be necessary to prevent rupture of the microcapsules on compression.
This leads to tablets that are unacceptably large. In some cases, however, it has been found possible to produce a tablet of acceptable si~e comprising microcapsules, but in these cases, both involving salicylic acid acetate, the size and shape of the salicylic acid acetate paxticles to be encapsulated must be carefully controlled and a low proportion of encapsulating material is used.
Polyethylene glycols have been used in small amounts as lubri-cantsinconventional tablets, but they have not previously been proposed as carriers in attempts to tablet microcapsules. The present invention is based on the observation that even brittle microcapsules can be tableted successfully, i.e. the microcap-sules retain their original properties, when a polyethylene glycol or another water-soluble, natural or synthetic waxy sub-stance having similar physical and mechanical properties to polyethylene glycol, hereafter termed "waxy-substance"~is used as carrier.
The present invention provides a tablet or another solid, shaped article produced by compression which comprises a microencapsu-led substance or a substance that is itself brittle or a substan-ce that has a brittle coating, and more than 2 % w/w, calcu-lated on the microcapsules, brittle substance or substance ha-ving a brittle coating, of a water-soluble natural or synthetic waxy substance having a melting point of at least 30 C, preferably ~1¢;~72 IIOE 77/F 272 within the range of from 30 to 100C.
The term "brittle" is used herein to denote a microencapsu-lated substance, a substance or a coating that would crack i~
tableted or formed into a solid, shaped article by compression in the absence of the waxy substance used in the present inven-tion.
The invention also provides a process for preparing the tablet or other solid, shaped article of the invention, which comprises admixing the microencapsulated substance, brittle sub--stance or substance having a brittle coating and the waxy sub-stance and, if desired, one or more carriers, and bringing the mixture into tablet form or the other desired compressed solid form, or applying a solution of the waxy substance i.n an organic solvent to the microencapsulated substance, brittle substance 1S or substance having a brittle coating, if desired, before or after admixture with one or more carriers, and bringi.ng the treated microencapsulated substance, brittle substance or sub-stance having a brittle coating and any carriers present into tablet form or the other desired compressed solid form.
The mixture may be tableted by any method, for example, direct compression, wet granulation or dry granulation, and the resulting tablets may be subjected to any post-treatment, for example, coating, lac~uering or sintering. Sintering has been found to be particularly advantageous, the sintering -tempera-ture preferably being about 10C above the melting point of the ~axy substance used. (The term "tablet" as used in this paragraph and hereafter includes the other solid, shaped ar-ticles, for example, pills, pellets and lozenges, produced by . -- 4 ~ 72 l~oE 77/F 272 compression, anc~'~ableting" includes the manufacture o~ such articles by compression.~
Substances having brittle coatings, which can be tableted successfully according to the invention, are those coated with for example an acrylic resin, ethylcellulose, nylon, ~lyceryl-monostearate or beeswaxy.
Any water-soluble, waxy substance having the required mel-ting point may be used in-the tablets of the invention, for example certain ethylene glycol derivatives, for example, poly-ethyleneglycol, and certain stearates, for example, sodiumstearate and polyoxyl 40 stearate. The preferred substance is polyethylene glycol (called "PEG" hereafter), which is avai]-able commercially in various grades, the number assigned to a grade as in PEG 2000 indicating the average molecular weight of the polymer.
Polyethyleneglycol has been used in the preparation of con-ventional tablets containing non-microencapsulated substances, but always in small amounts. We have found that when used in amounts of more than 2 %, which is about the previous limit, and preferably 5 % or more, the effect on microcapsules is quite unexpected. The accompanying drawing shows the effect of increasing amounts of PEG 6000 on the release rate of KCl from tablets containing microencapsulated KCl (KCl microcapsules being particular]y brittle), which is to decrease the number of microcapsules ruptured during tableting~ This effect occurs when the amounts o~ PEG 6000 exceeds 2 %.
The amount of the waxy substance used is therefore greater than 2 % w/w, calculated on the microcapsules, brittle substance, -~ ~7~ IIOE 77/E 272 or substance having a briitle coating, preferably 5 % or more and advantageously not more thar 10 ~. Upper limits are deter-mined by the size of the tablet, but in many cases amounts o~
waxy substance in excess o~ 10 ~ produce little more effect on the protection of the microcapsules, brittle substance, or substance having a brittle coating, so not more than 10 % is the advantageous amount of waxy carrier in many cases. In gene-ral, the upper limit of the waxy substance is 20 %.
Some of the waxy carriers are finely divided substances, ~or example, PEG 6000, which has a melting point within the range of from 55 to 60C, is available as a powder, but most of the other grades of PEG having suitable melting points are in the form of waxy flakes. It is necessary to mill such a sub-stance to a fine powder before use if it is to be admixed with the other components of the tablet. It is advisable to mill those grades having melting points in the lower end of the specified range in the presence of a cooling agent, e. y. 50 solid CO2, to prevent melting. This also applies to any other suitable substance that is available in a form other than a powder and that is to be admixed with the other components rather than applied in the form of a solution.
As mentioned above, other carriers may be present, and it is advisable, especially when tabletingmicrocapsules or other substances having a particularly brittle coat or particularly brittle substances to choose carriers that do not have sharp edges or corners. Microcrystalline cellulose, which has long, fibrous particles, is an example of a particularly suitable additional carrier. Other carriers which may be used are lactose, ~ 72 I~OE_77/~ 272 starches and sugars.
The microencapsulated substance, brittle substance or substance having a brittle coating may be any pharmacologi-cally active substance, for example, a drug, a dietary supp-lement or a vitamin, especially any substance for w}lich con-trolled release is required. This may be to enable release of the active substance in the duodenum or ileum rather than the stomach/ or to ensure that the active substance, for example, salicylic acid acetate, is released at a controlled rate in the stomach to decrease the chance of damage to the gastric mucosa.
The method of this invention has been found to be parti-cularly use~ul in the production of tablets comprising micro encapsulated potassium chloride, these microcapsules being particularly brittle. The potassium chloride tablets of the invention have disintegration times such that the microcapsules are readily released and dispersed in the stomach, thus avoiding a high local concentration of potassium chloride. Slow release microcapsules are especially used to reduce gastric irritation by causing release of the potassium chloride to occur slowly throughout the gastro-intestinal tract.
The preferred waxy substance for such tablets is a PEG, and the tablets are preferably sintered.
The tablets of the invention may comprise one active suh-stance in microencapsulated or coated form and ar,othe~ substan-ce or even the same substance in the matrix of the tahlet, again to provide controlled release, for example, tablets com-prising microencapsulated potassium chloride with a diuretic, ~ 7~ HOE 77/F 272 for example, frusemicle, in the matrix. The term "in the matrix"
means within the ta~let but outside the microcapsule or coated form.
In addition to tablets ~or pharmaceutical (including veterinary) use, the tablets of the invention may comprise, for example, fertili~ers, pesticides, disinfectants, or any other substance that is required per se in unit form or is re-quired in unit form for adding to a determined amount of water or other solvent to produce a solution of known strength. The tablets of the invention are a form of preparation that is not only more convenient but also safer to handle.
Further examples of substances for which slow release is advantageous are trace additives for water supplies, nutritio-nal and trace additives for fish ponds, and disinfection agents for swi~ning pools. Such substances may be microencapsulated or coated and tableted in accordance with the invention.
Microencapsulation or coating improve the stability of substances, and are particularly useful for preserving the ac-tivity if flavouring agents and vitamins, which are, accor-dingly, further suitable ingredients for the tablets of theinvention.
The following Examples illustrate the invention.
Tablets having the following composition were prepared:
ÇiOE 77/F 272 A B C D
mg mg mg mg KCl microcapsules 940 940 940 940 N-~2-furfuryl)-4-chloro- - - - 20 5-sulfamoyl-anthranilic acid Microcrystalline cellu- 94 94 94 94 lose Magnesium stearate 3 3 3 3 Amberlite IRP resin *100 100 100 100 Carbopol 934 10 10 10 10 The components were admixed thoroughly and compressed t:o tahlets. Tablets A to C, together with tablets having the same formulation except that they contain no PEG, were used to ob-tain the data presented in the accompanying drawing. Curve 1 shows the releasP from tablets containing no PEG, curves ~, 3 and 4 show the release from tablets corresponding to Example 1 B, A and C respectively. *Amberlite IRP resin is the po-tassium salt of a cross-linked carboxylic acid cation exchange resin~
It is used as a tablèt disintegrant and it is unlikely that it either contributes to the potassium ions released or binds the rPleased potassium ions.
Tablets were prepared as described in Example 1 ~ except ~ Je~ t~ 3J~ /?~,~
.' ' ' ' , .
~ 97 ~ HOE 77/F 272 that PEG 1000 was used instead of PEG 6000. The PEG 1000 was milled to a fine powder in the presence of 50 % solid CO2 be-fore use.
Tablets were prepared as described in Example 2 except that PEG 3~000 was used instead of PEG 1000.
Tablets were prepared as described in Example 2 except that instead of PEG 1000 there was used 50 % by weight of PEG 1000 and 50 % by weiyht of PEG 35000 Tablets were prepared as described in Examp]e 1A and were then sintered for 1 hour at 70 C. The hardness of the tablets was increased by this treatment.
Tablets were prepared as described in Exa~ple 1A and were then sugar coated in a coating pan using talc in syrup as the grossing coat and Tartrazine lake dispersed in syrup as the colour coating.
Tablets were prepared as described in Example 1 and were then film coated by spraying an aqueous solution of hydroxy-- propylmethylcellulose on to the tablets in a coating pan.
Tablets were prepared as described in Example 1A except that 20 mg of polyvinylpyrrolidone was used instead of the B Carbopol 934 G~ , Pt~ ~ ~r~d ~
:
37~ ~IOE 77/ F 272 Tablets ~ere prepared as described in Exa~ple 1A except that the microcrystalline cellu7ose was replaced by 94 mg of lactose.
Tablets were prepared as described in Example 1A except that the Arnberlite IRP resin was replaced by 100 rng starch.
Tablets were prepared as described in Example 1A except that the An~erlite IRP resin WaS replaced by 40 mg Primogel (ultra amylopectin).
EX~MPEE 12 Tablets having the following formula were prepared:
mg 1. KCl microcapsules 940 2. Lactose 94
have been made to produce tablets comprising microcapsules, but -2a-~ 72 ~ OR 77/F 272 again the problem is size: most microcapsules are very brittle so large amounts of carriers for example, mixtures of lactose, microcrystalline cellulose and starch, have been found to be necessary to prevent rupture of the microcapsules on compression.
This leads to tablets that are unacceptably large. In some cases, however, it has been found possible to produce a tablet of acceptable si~e comprising microcapsules, but in these cases, both involving salicylic acid acetate, the size and shape of the salicylic acid acetate paxticles to be encapsulated must be carefully controlled and a low proportion of encapsulating material is used.
Polyethylene glycols have been used in small amounts as lubri-cantsinconventional tablets, but they have not previously been proposed as carriers in attempts to tablet microcapsules. The present invention is based on the observation that even brittle microcapsules can be tableted successfully, i.e. the microcap-sules retain their original properties, when a polyethylene glycol or another water-soluble, natural or synthetic waxy sub-stance having similar physical and mechanical properties to polyethylene glycol, hereafter termed "waxy-substance"~is used as carrier.
The present invention provides a tablet or another solid, shaped article produced by compression which comprises a microencapsu-led substance or a substance that is itself brittle or a substan-ce that has a brittle coating, and more than 2 % w/w, calcu-lated on the microcapsules, brittle substance or substance ha-ving a brittle coating, of a water-soluble natural or synthetic waxy substance having a melting point of at least 30 C, preferably ~1¢;~72 IIOE 77/F 272 within the range of from 30 to 100C.
The term "brittle" is used herein to denote a microencapsu-lated substance, a substance or a coating that would crack i~
tableted or formed into a solid, shaped article by compression in the absence of the waxy substance used in the present inven-tion.
The invention also provides a process for preparing the tablet or other solid, shaped article of the invention, which comprises admixing the microencapsulated substance, brittle sub--stance or substance having a brittle coating and the waxy sub-stance and, if desired, one or more carriers, and bringing the mixture into tablet form or the other desired compressed solid form, or applying a solution of the waxy substance i.n an organic solvent to the microencapsulated substance, brittle substance 1S or substance having a brittle coating, if desired, before or after admixture with one or more carriers, and bringi.ng the treated microencapsulated substance, brittle substance or sub-stance having a brittle coating and any carriers present into tablet form or the other desired compressed solid form.
The mixture may be tableted by any method, for example, direct compression, wet granulation or dry granulation, and the resulting tablets may be subjected to any post-treatment, for example, coating, lac~uering or sintering. Sintering has been found to be particularly advantageous, the sintering -tempera-ture preferably being about 10C above the melting point of the ~axy substance used. (The term "tablet" as used in this paragraph and hereafter includes the other solid, shaped ar-ticles, for example, pills, pellets and lozenges, produced by . -- 4 ~ 72 l~oE 77/F 272 compression, anc~'~ableting" includes the manufacture o~ such articles by compression.~
Substances having brittle coatings, which can be tableted successfully according to the invention, are those coated with for example an acrylic resin, ethylcellulose, nylon, ~lyceryl-monostearate or beeswaxy.
Any water-soluble, waxy substance having the required mel-ting point may be used in-the tablets of the invention, for example certain ethylene glycol derivatives, for example, poly-ethyleneglycol, and certain stearates, for example, sodiumstearate and polyoxyl 40 stearate. The preferred substance is polyethylene glycol (called "PEG" hereafter), which is avai]-able commercially in various grades, the number assigned to a grade as in PEG 2000 indicating the average molecular weight of the polymer.
Polyethyleneglycol has been used in the preparation of con-ventional tablets containing non-microencapsulated substances, but always in small amounts. We have found that when used in amounts of more than 2 %, which is about the previous limit, and preferably 5 % or more, the effect on microcapsules is quite unexpected. The accompanying drawing shows the effect of increasing amounts of PEG 6000 on the release rate of KCl from tablets containing microencapsulated KCl (KCl microcapsules being particular]y brittle), which is to decrease the number of microcapsules ruptured during tableting~ This effect occurs when the amounts o~ PEG 6000 exceeds 2 %.
The amount of the waxy substance used is therefore greater than 2 % w/w, calculated on the microcapsules, brittle substance, -~ ~7~ IIOE 77/E 272 or substance having a briitle coating, preferably 5 % or more and advantageously not more thar 10 ~. Upper limits are deter-mined by the size of the tablet, but in many cases amounts o~
waxy substance in excess o~ 10 ~ produce little more effect on the protection of the microcapsules, brittle substance, or substance having a brittle coating, so not more than 10 % is the advantageous amount of waxy carrier in many cases. In gene-ral, the upper limit of the waxy substance is 20 %.
Some of the waxy carriers are finely divided substances, ~or example, PEG 6000, which has a melting point within the range of from 55 to 60C, is available as a powder, but most of the other grades of PEG having suitable melting points are in the form of waxy flakes. It is necessary to mill such a sub-stance to a fine powder before use if it is to be admixed with the other components of the tablet. It is advisable to mill those grades having melting points in the lower end of the specified range in the presence of a cooling agent, e. y. 50 solid CO2, to prevent melting. This also applies to any other suitable substance that is available in a form other than a powder and that is to be admixed with the other components rather than applied in the form of a solution.
As mentioned above, other carriers may be present, and it is advisable, especially when tabletingmicrocapsules or other substances having a particularly brittle coat or particularly brittle substances to choose carriers that do not have sharp edges or corners. Microcrystalline cellulose, which has long, fibrous particles, is an example of a particularly suitable additional carrier. Other carriers which may be used are lactose, ~ 72 I~OE_77/~ 272 starches and sugars.
The microencapsulated substance, brittle substance or substance having a brittle coating may be any pharmacologi-cally active substance, for example, a drug, a dietary supp-lement or a vitamin, especially any substance for w}lich con-trolled release is required. This may be to enable release of the active substance in the duodenum or ileum rather than the stomach/ or to ensure that the active substance, for example, salicylic acid acetate, is released at a controlled rate in the stomach to decrease the chance of damage to the gastric mucosa.
The method of this invention has been found to be parti-cularly use~ul in the production of tablets comprising micro encapsulated potassium chloride, these microcapsules being particularly brittle. The potassium chloride tablets of the invention have disintegration times such that the microcapsules are readily released and dispersed in the stomach, thus avoiding a high local concentration of potassium chloride. Slow release microcapsules are especially used to reduce gastric irritation by causing release of the potassium chloride to occur slowly throughout the gastro-intestinal tract.
The preferred waxy substance for such tablets is a PEG, and the tablets are preferably sintered.
The tablets of the invention may comprise one active suh-stance in microencapsulated or coated form and ar,othe~ substan-ce or even the same substance in the matrix of the tahlet, again to provide controlled release, for example, tablets com-prising microencapsulated potassium chloride with a diuretic, ~ 7~ HOE 77/F 272 for example, frusemicle, in the matrix. The term "in the matrix"
means within the ta~let but outside the microcapsule or coated form.
In addition to tablets ~or pharmaceutical (including veterinary) use, the tablets of the invention may comprise, for example, fertili~ers, pesticides, disinfectants, or any other substance that is required per se in unit form or is re-quired in unit form for adding to a determined amount of water or other solvent to produce a solution of known strength. The tablets of the invention are a form of preparation that is not only more convenient but also safer to handle.
Further examples of substances for which slow release is advantageous are trace additives for water supplies, nutritio-nal and trace additives for fish ponds, and disinfection agents for swi~ning pools. Such substances may be microencapsulated or coated and tableted in accordance with the invention.
Microencapsulation or coating improve the stability of substances, and are particularly useful for preserving the ac-tivity if flavouring agents and vitamins, which are, accor-dingly, further suitable ingredients for the tablets of theinvention.
The following Examples illustrate the invention.
Tablets having the following composition were prepared:
ÇiOE 77/F 272 A B C D
mg mg mg mg KCl microcapsules 940 940 940 940 N-~2-furfuryl)-4-chloro- - - - 20 5-sulfamoyl-anthranilic acid Microcrystalline cellu- 94 94 94 94 lose Magnesium stearate 3 3 3 3 Amberlite IRP resin *100 100 100 100 Carbopol 934 10 10 10 10 The components were admixed thoroughly and compressed t:o tahlets. Tablets A to C, together with tablets having the same formulation except that they contain no PEG, were used to ob-tain the data presented in the accompanying drawing. Curve 1 shows the releasP from tablets containing no PEG, curves ~, 3 and 4 show the release from tablets corresponding to Example 1 B, A and C respectively. *Amberlite IRP resin is the po-tassium salt of a cross-linked carboxylic acid cation exchange resin~
It is used as a tablèt disintegrant and it is unlikely that it either contributes to the potassium ions released or binds the rPleased potassium ions.
Tablets were prepared as described in Example 1 ~ except ~ Je~ t~ 3J~ /?~,~
.' ' ' ' , .
~ 97 ~ HOE 77/F 272 that PEG 1000 was used instead of PEG 6000. The PEG 1000 was milled to a fine powder in the presence of 50 % solid CO2 be-fore use.
Tablets were prepared as described in Example 2 except that PEG 3~000 was used instead of PEG 1000.
Tablets were prepared as described in Example 2 except that instead of PEG 1000 there was used 50 % by weight of PEG 1000 and 50 % by weiyht of PEG 35000 Tablets were prepared as described in Examp]e 1A and were then sintered for 1 hour at 70 C. The hardness of the tablets was increased by this treatment.
Tablets were prepared as described in Exa~ple 1A and were then sugar coated in a coating pan using talc in syrup as the grossing coat and Tartrazine lake dispersed in syrup as the colour coating.
Tablets were prepared as described in Example 1 and were then film coated by spraying an aqueous solution of hydroxy-- propylmethylcellulose on to the tablets in a coating pan.
Tablets were prepared as described in Example 1A except that 20 mg of polyvinylpyrrolidone was used instead of the B Carbopol 934 G~ , Pt~ ~ ~r~d ~
:
37~ ~IOE 77/ F 272 Tablets ~ere prepared as described in Exa~ple 1A except that the microcrystalline cellu7ose was replaced by 94 mg of lactose.
Tablets were prepared as described in Example 1A except that the Arnberlite IRP resin was replaced by 100 rng starch.
Tablets were prepared as described in Example 1A except that the An~erlite IRP resin WaS replaced by 40 mg Primogel (ultra amylopectin).
EX~MPEE 12 Tablets having the following formula were prepared:
mg 1. KCl microcapsules 940 2. Lactose 94
3. Starch 100
4. Polyvinylpyrrolidone 20
5. PEG 6000 94
6. Magnesium stearate 3 Components 2, 3, 5 and 6 were granulated with component 4 dissolved in water. The granulation was carried out by wet massing and screening in a planetary mixer, by using a high speed mixer-granulator and by spray granulation. In each case, the resulting granules were dried, mixed with cornponent 1, and compressed into tablets.
fiOJ(-('J ~3J~ k . ~ . -E~AMPLE 1 3 Tablets having the formula given in Example 12 were pre-pared by mixing components 2, 3, 4, 5 and 6 and dry granula-ting the mixture by slugging on a tablet machine, and by means of a compactor. In each case, the resulting granules were crushed, passed through a screen having a 1 mm mesh size, mixed with the microcapsules of KCl, and compressed into tablets.
EXAMPLE 1~
Tablets were prepared as described in Example 1A and Example 9, in each case replacing the magnesium stearate by 3 mg of stearic acid.
fiOJ(-('J ~3J~ k . ~ . -E~AMPLE 1 3 Tablets having the formula given in Example 12 were pre-pared by mixing components 2, 3, 4, 5 and 6 and dry granula-ting the mixture by slugging on a tablet machine, and by means of a compactor. In each case, the resulting granules were crushed, passed through a screen having a 1 mm mesh size, mixed with the microcapsules of KCl, and compressed into tablets.
EXAMPLE 1~
Tablets were prepared as described in Example 1A and Example 9, in each case replacing the magnesium stearate by 3 mg of stearic acid.
Claims (12)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A tablet produced by compression which comprises a microencapsulated substance dispersed in a matrix comprising a water-soluble natural or synthetic waxy substance having a melting point of at least 30°C selected from the group consist-ing of ethylene glycol derivatives and stearates, the waxy substance being present in an amount of from 2 to 20% by weight, calculated on the weight of the microencapsulated substance.
2. A tablet as claimed in claim 1, wherein the waxy substance has a melting point within the range of from 30 to 100°C.
3. A tablet as claimed in claim 1 or claim 2 wherein the waxy substance is a polyethylene glycol.
4. A tablet as claimed in claim 1 or claim 2 which also comprises one or more pharmaceutically acceptable carriers.
5. A tablet as claimed in claim 1 or claim 2 wherein the microencapsulated substance is a pharmacologically active substance, a fertilizer, a pesticide, a disinfectant, a nutritional or trace substance, or a flavouring agent.
6. A tablet as claimed in claim 1 or claim 2 wherein the microencapsulated substance is potassium chloride.
7. A tablet as claimed in claim 1 or claim 2 which has been sintered.
8. A process for the preparation of a tablet as claimed in claim 1, which comprises dispersing the microencapsulated sub-stance in the water-soluble natural or synthetic waxy substance, the waxy substance being present in an amount of from 2 to 20% by weight of the microencapsulated substance, and bringing the mixture into tablet form.
9. A process as claimed in claim 8 in which the waxy substance is applied in the form of a solution in an organic solvent.
10. A process as claimed in claim 8 in which at least one carrier is added to the dispersion.
11. A process as claimed in claim 8, claim 9 or claim 10, wherein the article is further subjected to sintering.
12. A process as claimed in claim 8, claim 9 or claim 10, wherein the article is subjected to sintering at a temperature about 10°C above the melting point of the waxy substance used.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB13855/77 | 1977-04-01 | ||
| GB13855/77A GB1598458A (en) | 1977-04-01 | 1977-04-01 | Tableting of microcapsules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1110972A true CA1110972A (en) | 1981-10-20 |
Family
ID=10030606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA300,184A Expired CA1110972A (en) | 1977-04-01 | 1978-03-31 | Tableting of microcapsules |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS53142520A (en) |
| AU (1) | AU523028B2 (en) |
| BE (1) | BE865633A (en) |
| CA (1) | CA1110972A (en) |
| CH (1) | CH640727A5 (en) |
| DE (1) | DE2813146A1 (en) |
| DK (1) | DK143078A (en) |
| FR (1) | FR2385388B1 (en) |
| GB (1) | GB1598458A (en) |
| IT (1) | IT1095559B (en) |
| NL (1) | NL7803496A (en) |
| SE (1) | SE7803661L (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631024A (en) * | 1995-05-22 | 1997-05-20 | Enviroquest, Ltd. | Medicaments for beneficial insects and method |
| US8815289B2 (en) | 2006-08-25 | 2014-08-26 | Purdue Pharma L.P. | Tamper resistant dosage forms |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5873359A (en) * | 1981-10-27 | 1983-05-02 | 旭化成株式会社 | Production of pharmaceutical tablet |
| US4749575A (en) * | 1983-10-03 | 1988-06-07 | Bio-Dar Ltd. | Microencapsulated medicament in sweet matrix |
| CA1266235A (en) * | 1985-03-25 | 1990-02-27 | Wallace E. Becker | Tablet composition for drug combinations |
| US4863741A (en) * | 1985-03-25 | 1989-09-05 | Abbott Laboratories | Tablet composition for drug combinations |
| CA1259924A (en) * | 1985-03-25 | 1989-09-26 | Wallace E. Becker | Pharmaceutical tableting method |
| DE3532692A1 (en) * | 1985-09-13 | 1987-03-19 | Boehringer Mannheim Gmbh | METHOD FOR PRODUCING TABLETS FROM PELLETS |
| WO1987006129A1 (en) * | 1986-04-10 | 1987-10-22 | Daratech Pty. Ltd. | Vaccine and implant |
| US6024983A (en) * | 1986-10-24 | 2000-02-15 | Southern Research Institute | Composition for delivering bioactive agents for immune response and its preparation |
| US5009897A (en) * | 1988-06-24 | 1991-04-23 | Abbott Laboratories | Pharmaceutical granules and tablets made therefrom |
| JP2514078B2 (en) * | 1988-08-22 | 1996-07-10 | エスエス製薬株式会社 | Compressed formulation |
| WO1990007327A1 (en) * | 1988-12-28 | 1990-07-12 | Taisho Pharmaceutical Co., Ltd. | Stress scattering method in tableting |
| DE3933000A1 (en) * | 1989-10-03 | 1991-04-11 | Int Pharma Agentur | Erosion-controlled active agent release system |
| EP0418596A3 (en) * | 1989-09-21 | 1991-10-23 | American Cyanamid Company | Controlled release pharmaceutical compositions from spherical granules in tabletted oral dosage unit form |
| US5281420A (en) * | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| US5436011A (en) * | 1993-04-16 | 1995-07-25 | Bristol-Myers Squibb Company | Solid pharmaceutical dosage form and a method for reducing abrasion |
| GB9921933D0 (en) * | 1999-09-17 | 1999-11-17 | Univ Gent | Solid shaped articles comprising biologically active substances and a method for their production |
| US6419954B1 (en) * | 2000-05-19 | 2002-07-16 | Yamanouchi Pharmaceutical Co., Ltd. | Tablets and methods for modified release of hydrophilic and other active agents |
| EP1302304B1 (en) | 2000-06-20 | 2011-12-14 | Sanwa Kagaku Kenkyusho Co., Ltd. | Method of producing a nucleated molded article |
| CN100497445C (en) * | 2000-07-05 | 2009-06-10 | 旭化成株式会社 | Cellulose powder |
| DE60144524D1 (en) * | 2000-09-01 | 2011-06-09 | Palmaya Pty Ltd | PHARMACEUTICAL PREPARATION AND METHOD TO DISPOSE THIS |
| US8101209B2 (en) | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
| US20030190343A1 (en) * | 2002-03-05 | 2003-10-09 | Pfizer Inc. | Palatable pharmaceutical compositions for companion animals |
| FR2837100B1 (en) * | 2002-03-18 | 2004-07-23 | Flamel Tech Sa | MODIFIED RELEASE MICROCAPSULE-BASED TABLETS |
| FR2838647B1 (en) * | 2002-04-23 | 2006-02-17 | PROLONGED RELEASE PARTICLES, PROCESS FOR THEIR PREPARATION AND TABLETS CONTAINING SAME | |
| US20060263429A1 (en) | 2005-05-20 | 2006-11-23 | Hengsheng Feng | Compressible mixture, compressed pharmaceutical compositions, and method of preparation thereof |
| AU2010211985A1 (en) * | 2009-01-22 | 2011-08-11 | Abbott Healthcare Private Limited | Chronotherapeutic pharmaceutical composition |
| US9566248B2 (en) | 2013-09-13 | 2017-02-14 | R.P. Scherer Technologies, Llc | Encased-pellet tablets |
| CN112490052A (en) | 2020-11-19 | 2021-03-12 | 深圳市致尚科技股份有限公司 | Multi-directional input device |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE575775A (en) * | 1958-02-18 | |||
| SE363974B (en) * | 1964-05-20 | 1974-02-11 | Bristol Myers Co | |
| AU418370B2 (en) * | 1965-05-11 | 1971-11-02 | Compositions for anorectic use | |
| US3487138A (en) * | 1966-11-23 | 1969-12-30 | Merck & Co Inc | Process for preparing a delayed release medicinal tablet |
| DE1617363B1 (en) * | 1967-12-06 | 1972-05-31 | Boehringer & Soehne Gmbh | Process for the production of highly active enzyme digestive preparations |
| US3557279A (en) * | 1969-06-12 | 1971-01-19 | Merck & Co Inc | Microencapsulation form of an anti-inflammatory drug |
| NL7112083A (en) * | 1970-09-16 | 1972-03-20 |
-
1977
- 1977-04-01 GB GB13855/77A patent/GB1598458A/en not_active Expired
-
1978
- 1978-03-25 DE DE19782813146 patent/DE2813146A1/en not_active Withdrawn
- 1978-03-29 CH CH336478A patent/CH640727A5/en not_active IP Right Cessation
- 1978-03-30 IT IT21797/78A patent/IT1095559B/en active
- 1978-03-31 AU AU34651/78A patent/AU523028B2/en not_active Expired
- 1978-03-31 JP JP3874478A patent/JPS53142520A/en active Pending
- 1978-03-31 NL NL7803496A patent/NL7803496A/en not_active Application Discontinuation
- 1978-03-31 CA CA300,184A patent/CA1110972A/en not_active Expired
- 1978-03-31 SE SE7803661A patent/SE7803661L/en unknown
- 1978-03-31 DK DK143078A patent/DK143078A/en not_active Application Discontinuation
- 1978-03-31 FR FR7809666A patent/FR2385388B1/fr not_active Expired
- 1978-04-03 BE BE186523A patent/BE865633A/en not_active IP Right Cessation
Cited By (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631024A (en) * | 1995-05-22 | 1997-05-20 | Enviroquest, Ltd. | Medicaments for beneficial insects and method |
| US8815289B2 (en) | 2006-08-25 | 2014-08-26 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US8821929B2 (en) | 2006-08-25 | 2014-09-02 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US8834925B2 (en) | 2006-08-25 | 2014-09-16 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US8846086B2 (en) | 2006-08-25 | 2014-09-30 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US8894988B2 (en) | 2006-08-25 | 2014-11-25 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US8894987B2 (en) | 2006-08-25 | 2014-11-25 | William H. McKenna | Tamper resistant dosage forms |
| US8911719B2 (en) | 2006-08-25 | 2014-12-16 | Purdue Pharma Lp | Tamper resistant dosage forms |
| US9084816B2 (en) | 2006-08-25 | 2015-07-21 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9095614B2 (en) | 2006-08-25 | 2015-08-04 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9095615B2 (en) | 2006-08-25 | 2015-08-04 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9101661B2 (en) | 2006-08-25 | 2015-08-11 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9763933B2 (en) | 2006-08-25 | 2017-09-19 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9763886B2 (en) | 2006-08-25 | 2017-09-19 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9770416B2 (en) | 2006-08-25 | 2017-09-26 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9770417B2 (en) | 2006-08-25 | 2017-09-26 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9775808B2 (en) | 2006-08-25 | 2017-10-03 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9775810B2 (en) | 2006-08-25 | 2017-10-03 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9775811B2 (en) | 2006-08-25 | 2017-10-03 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9775812B2 (en) | 2006-08-25 | 2017-10-03 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US9775809B2 (en) | 2006-08-25 | 2017-10-03 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US10076499B2 (en) | 2006-08-25 | 2018-09-18 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US10076498B2 (en) | 2006-08-25 | 2018-09-18 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11298322B2 (en) | 2006-08-25 | 2022-04-12 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11304909B2 (en) | 2006-08-25 | 2022-04-19 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11304908B2 (en) | 2006-08-25 | 2022-04-19 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11826472B2 (en) | 2006-08-25 | 2023-11-28 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11904055B2 (en) | 2006-08-25 | 2024-02-20 | Purdue Pharma L.P. | Tamper resistant dosage forms |
| US11938225B2 (en) | 2006-08-25 | 2024-03-26 | Purdue Pharm L.P. | Tamper resistant dosage forms |
| US11964056B1 (en) | 2006-08-25 | 2024-04-23 | Purdue Pharma L.P | Tamper resistant dosage forms |
Also Published As
| Publication number | Publication date |
|---|---|
| SE7803661L (en) | 1978-10-02 |
| BE865633A (en) | 1978-10-03 |
| JPS53142520A (en) | 1978-12-12 |
| IT1095559B (en) | 1985-08-10 |
| DE2813146A1 (en) | 1978-10-19 |
| NL7803496A (en) | 1978-10-03 |
| CH640727A5 (en) | 1984-01-31 |
| FR2385388B1 (en) | 1980-07-25 |
| FR2385388A1 (en) | 1978-10-27 |
| AU523028B2 (en) | 1982-07-08 |
| DK143078A (en) | 1978-10-02 |
| IT7821797A0 (en) | 1978-03-30 |
| GB1598458A (en) | 1981-09-23 |
| AU3465178A (en) | 1979-10-04 |
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Legal Events
| Date | Code | Title | Description |
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| MKEX | Expiry |