WO1996018370A1 - Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process - Google Patents

Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process Download PDF

Info

Publication number
WO1996018370A1
WO1996018370A1 PCT/US1995/014651 US9514651W WO9618370A1 WO 1996018370 A1 WO1996018370 A1 WO 1996018370A1 US 9514651 W US9514651 W US 9514651W WO 9618370 A1 WO9618370 A1 WO 9618370A1
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
capsule
solid dosage
form according
range
Prior art date
Application number
PCT/US1995/014651
Other languages
French (fr)
Inventor
James Amey
Dominique Cade
Paul Maes
Robert Scott
Original Assignee
Warner-Lambert Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Warner-Lambert Company filed Critical Warner-Lambert Company
Priority to CA002205553A priority Critical patent/CA2205553C/en
Priority to MX9703773A priority patent/MX9703773A/en
Priority to JP51881996A priority patent/JP3670016B2/en
Priority to DE69518006T priority patent/DE69518006T2/en
Priority to DK95939890T priority patent/DK0797424T3/en
Priority to AT95939890T priority patent/ATE194486T1/en
Priority to EP95939890A priority patent/EP0797424B1/en
Publication of WO1996018370A1 publication Critical patent/WO1996018370A1/en
Priority to GR20000402180T priority patent/GR3034491T3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • A61J3/071—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
    • A61J3/072—Sealing capsules, e.g. rendering them tamper-proof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • A61J3/071—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release

Definitions

  • the present invention relates to a process for encapsulation of caplets in a capsule and to solid dosage forms obtainable by such a process, and more particularly, to the manufacture of a tamper-proof capsule containing a pharmaceutically active composition.
  • caplets Various oral medications have been manufactured in the form of so called caplets, which can be swallowed by patients during their regiment of taking medication.
  • Caplets are not as easily swallowed by patients as capsules having, for example, a gelatin coating.
  • capsule coatings are desirable over caplets since the coatings provide a neutral taste in contrast to caplets per se which sometimes contain pharmaceutical substances that taste, for example, bitter.
  • patients, in particular children refuse to swallow such caplets per se. Attempts have therefore been made to encapsulate caplets in a capsule by means of a gelatin cover.
  • U.S. Patent No. 4,867,983 to Berta describes a method for double dipping gelatin coated caplets.
  • the method provides a procedure for coating solid cores, such as caplets, with a first gelatinous coating on one end, and then with a second gelatinous coating on the other end which is thicker than the first, to simulate the interlocking halves of a hollow capsule.
  • the second, thicker gelatinous coating can be provided with a single gelatin coating from a bath having a higher viscosity than the bath used to provide the first gelatinous coating.
  • the second gelatinous coating can be provided by double dipping to provide layers of gelatinous material or gelatin.
  • an automatic caplet filler for filling normal gelatin capsules with caplets.
  • the capsules formed by this automatic caplet filler are disadvantageous in that they can be easily manipulated. Sealing of the capsules has to be effected by means of an additional gelatin strip or by gluing of the caplets in the capsule with an adhesive, as e.g. described in U.S. Patent No. 4,928,840 or European Patent Application No.
  • This further treatment of the capsules may have the effect that substances other than the medication are encapsulated in the capsule. If on one hand a water-based adhesive is used for gluing the capsule halves together, the capsule as well as the caplet may be deformed. If on the other hand, an adhesive containing an organic solvent is used, a brittleness of the capsule will be the result. Finally, if the capsule halves are connected with each other by means of a heat shrinking process, a visible gap will remain between the capsule halves.
  • the present invention provides a process for encapsulation of a caplet in a capsule by cold shrinking together capsule parts, which are filled with a caplet.
  • the present invention provides a solid dosage form obtainable by such a process.
  • the solid dosage form according to the present invention is tamper-proof in that the caplet contained in the capsule cannot be removed from the capsule without destroying same.
  • the process according to the present invention furthermore provides a capsule product comprising several parts, which are combined with each other in a way that no visible slits between the capsule parts are present after the cold shrink procedure.
  • the solid dosage forms of the present invention have a completely smooth surface, so that same can be swallowed easily by patients. More specifically, a process for encapsulating caplets in a capsule is provided, which comprises the following steps: a. providing empty capsule parts, b. filling at least one of said capsule parts with one or more caplets, c. putting said capsule parts together, and d. treating the combined capsule parts by cold shrinking.
  • the capsule shell in which the caplet is to be enclosed preferably comprises two shell halves, a body portion and a cap portion. Other capsules comprising more than two parts are also possible.
  • the capsule is typically a hollow shell of generally cylindrical shape having a diameter and length sufficient so that the caplet fits appropriately in the empty capsule.
  • the clearance of the capsule shell and the caplet is preferably about + 0.5 mm. According to a specifically preferred embodiment of the present invention, the clearance of the capsule shell and the caplet is in the range of from about 0 to to about -0.5 mm, which means that the caplet is compressed in the capsule.
  • a specifically preferred process of the present invention is carried out as follows. Empty capsule shell parts are either kept after production at humid conditions in the range of from about 40 to about 90 %, particularly from about 60 to about 80 %, relative humidity to retain a moisture content of from about 16 to about 18 % by weight of the capsule shell or are re-humidified to said moisture content before feeding into a capsule filling machine.
  • the first capsule shell part is then kept under humid conditions within the filling machine at said moisture content during rectifying and assembling with a caplet having a moisture content in the range of from about 0 to about 12 % by weight.
  • a second or further capsule shell part is processed in the same matter as the first one.
  • the encapsulated dosage form is dried at a relative humidity in the range of from about 20 to about 40 % and a temperature in the range of from about 15 to about 60 C, preferably from about 15 to about 40 C, more preferably from about 18 to about 25 C.
  • Caplets having a low moisture content of in the range of from about 0 to about 6 % by weight, or more preferably of from about 0 to about 3 % by weight, are especially suitable to be used in the process of the present invention.
  • Conical ends of the caplet make the insertion of the caplet into one half of the capsule easier.
  • the capsule After drying and shrinking the capsule parts together, the capsule can be further film coated, which coating may be enteric.
  • the capsule shell material can be a hydrophilic polymer, gelatin being the preferred choice.
  • suitable capsule shell materials include starch, casein, chitosan, soya bean protein, safflower protein, alginates, gellan gum, carrageenan, xanthan gum, phtalated gelatin, succinated gelatin, cellulosephtalate-acetate, polyvinylacetate, hydroxypropyl methylcellulose, polyvinylacetate-phtalate, polymerisates of acrylic or mthacrylic esters or mixtures thereof.
  • the capsule shell material may furthermore contain from about 0 to about 40 % pharmaceutically acceptable plasticizers based upon the weight of the hydrophilic polymer.
  • the plasticizer which may be employed can be selected from polyethylene glycol, glycerol, sorbitol, dioctyl-sodium sulfosuccinate, triethyl citrate, tributyl citrate, 1,2-propyleneglycol, mono-, di, or tri-acetates of glycerol or mixtures thereof.
  • the capsule shell material may contain pharmaceutically acceptable lubricants in the range of from about 0 to about 10% based upon the weight of the hydrophilic polymer.
  • the lubricant may be selected from aluminiumstearate, calciumstearate, magnesiumstearate, tinstearate, talc, sodium lauryl sulfate, lecithins, mineral oils, stearic acid or silicones or mixtures thereof.
  • the capsule shell material may contain pharmaceutically acceptable coloring agents in the range of from about 0 to about 10 % based upon the weight of the hydrophilic polymer.
  • the coloring agent may be selected from azo-quinophthalone-, triphenylmethane- , xanthene-dyes, iron oxides or hydroxides, titanium dioxide or natural dyes or mixtures thereof. Further suitable coloring agents are sunset yellow, allura red, amaranth, cochineal red, azogeranine, tartrazine, brilliant black, canthaxanthin, patent blue, fast green, brilliant blue, acid green, erythrosine, q inoline yellow, indigotine, curcumin or carbon black.
  • the capsule shell material may contain pharmaceutically acceptable extenders in the range of from about 0 to about 95 % based upon the weight of the hydrophilic polymer.
  • the extender may be selected from sunflower proteins, soybean proteins, cotton seed proteins, peanut proteins, rape seed proteins, lactose, gum arabic, acrylates or methacrylates, cellulose acetyl phthalates, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulosephthalate, hydroxymethylcellulose, polyvinylpyrrolidone, shellac, bentonite, polyvinyl-acetatephtalate, phthalated gelatin, succinated gelatin, agar agar, hydroxyalkylstarches or mixtures thereof.
  • the solid pharmaceutical dosage form according to the present invention also may comprise a coating selected from cellacephate, polyvinyl acetate phthalate, methacrylic acid polymers, hypromellose phthalate, hydroxyalkyl methyl cellulose phthalates or mixtures thereof.
  • the capsule parts of the solid dosage form of the present invention may have the same or different lengths and/or the same or different color.
  • the solid dosage form In the contact area of the capsule parts, the solid dosage form may be banded or easily dividable.
  • the caplet being contained in the capsule can have a preformed step or groove in the dividing position of the capsule.
  • the caplet can be coated with an acceptable coating for tablet processing. In some cases, uncoated caplets are, however, preferred.
  • a better contact between the inner shells of the capsule parts and the caplets can be obtained by treating the inner shells and/or the surface of the caplet with an adhesive.
  • a suitable technique to apply the adhesive is spraying same on the shells and caplets immediately before assembling same.
  • Suitable adhesives are e.g. tackidex or an aqueous gelatin solution.
  • the solid dosage form according to the present invention may, for example, comprise a pharmaceutically or agrochemically active composition. Furthermore comprised in the solid dosage form can, for example, be a foodstuff or a dyestuff composition.
  • the active substance of same can, for example, be selected from betamethason, thioctacid, sotalol, salbutamol, norfenefrin, silymarin, dihydergotamin, buflomedil, etofibrat, indometacin, oxazepam, acetyldigoxin, piroxicam, haloperidol, isosorbide mononitrate, amitriptylin, diclofenac, nifedipin, verapamil, pyritinol, nitrendipin, doxycyclin, bromhexin, methylprednisolon, clonidin, fenofibrat, allopurinol, pirenzepin, levothyroxin, tamoxifen, metildigoxin, o- ( ⁇ -hydroxyethyl) -ruto

Abstract

A process for encapsulation of caplets in a capsule comprises the following steps: a) providing empty capsule parts; b) filling at least one of said capsule parts with one or more caplets; c) putting said capsule parts together; and d) treating the combined parts by cold shrinking. The solid dosage forms obtainable by such a process are tamper-proof in that they cannot be opened in a way to be reassembled without showing such opening process.

Description

PROCESS FOR ENCAPSULATION OF CAPLETS IN A CAPSULE AND SOLID DOSAGE FORMS OBTAINABLE BY SUCH PROCESS
Field of the Invention
The present invention relates to a process for encapsulation of caplets in a capsule and to solid dosage forms obtainable by such a process, and more particularly, to the manufacture of a tamper-proof capsule containing a pharmaceutically active composition.
Background of the Invention
Various oral medications have been manufactured in the form of so called caplets, which can be swallowed by patients during their regiment of taking medication. Caplets, however, are not as easily swallowed by patients as capsules having, for example, a gelatin coating. Additionally, capsule coatings are desirable over caplets since the coatings provide a neutral taste in contrast to caplets per se which sometimes contain pharmaceutical substances that taste, for example, bitter. Thus, patients, in particular children, refuse to swallow such caplets per se. Attempts have therefore been made to encapsulate caplets in a capsule by means of a gelatin cover.
U.S. Patent No. 4,867,983 to Berta describes a method for double dipping gelatin coated caplets. The method provides a procedure for coating solid cores, such as caplets, with a first gelatinous coating on one end, and then with a second gelatinous coating on the other end which is thicker than the first, to simulate the interlocking halves of a hollow capsule. The second, thicker gelatinous coating can be provided with a single gelatin coating from a bath having a higher viscosity than the bath used to provide the first gelatinous coating. Alternatively, the second gelatinous coating can be provided by double dipping to provide layers of gelatinous material or gelatin. This known coating is disadvantageous in that the gelatinous coating and the color distribution is not uniformly distributed over the caplets by this process. Moreover, an overlapping of the different coatings results in color changes of the coatings. Additionally, the dip margins obtained by the known process tend not to be straight. Furthermore, the coatings according to the above patent chip off under stress if the coated caplets are stored under dry conditions and/or high temperature. Finally, the dip coating process of U.S. Patent No. 4,867,983 is time consuming and expensive.
From U.S. Patent No. 5,081,822 to Boyd et al, an automatic caplet filler is known for filling normal gelatin capsules with caplets. The capsules formed by this automatic caplet filler, however, are disadvantageous in that they can be easily manipulated. Sealing of the capsules has to be effected by means of an additional gelatin strip or by gluing of the caplets in the capsule with an adhesive, as e.g. described in U.S. Patent No. 4,928,840 or European Patent Application No.
0435726. This further treatment of the capsules may have the effect that substances other than the medication are encapsulated in the capsule. If on one hand a water-based adhesive is used for gluing the capsule halves together, the capsule as well as the caplet may be deformed. If on the other hand, an adhesive containing an organic solvent is used, a brittleness of the capsule will be the result. Finally, if the capsule halves are connected with each other by means of a heat shrinking process, a visible gap will remain between the capsule halves.
It is therefore the object of the present invention to provide a method for encapsulating caplets in a capsule in a tamper-proof form. It is yet another object of the invention to provide a cost-effective process for easily manufacturing tamper-proof solid dosage forms. It is yet another object of the present invention to provide a solid dosage form comprising a caplet covered by a capsule. It is yet another object of the present invention to provide a pharmaceutical dosage form having a greater resistance to breaking than known products. A further object of the present invention is to provide a tamper-proof solid dosage form.
Summary of the Invention
According to a first aspect, the present invention provides a process for encapsulation of a caplet in a capsule by cold shrinking together capsule parts, which are filled with a caplet. According to another aspect, the present invention provides a solid dosage form obtainable by such a process. The solid dosage form according to the present invention is tamper-proof in that the caplet contained in the capsule cannot be removed from the capsule without destroying same.
The process according to the present invention furthermore provides a capsule product comprising several parts, which are combined with each other in a way that no visible slits between the capsule parts are present after the cold shrink procedure. The solid dosage forms of the present invention have a completely smooth surface, so that same can be swallowed easily by patients. More specifically, a process for encapsulating caplets in a capsule is provided, which comprises the following steps: a. providing empty capsule parts, b. filling at least one of said capsule parts with one or more caplets, c. putting said capsule parts together, and d. treating the combined capsule parts by cold shrinking.
Moreover, a solid dosage form comprising a caplet and a capsule coating obtainable by such process is described.
Description of Preferred Embodiments of the Invention
The capsule shell in which the caplet is to be enclosed preferably comprises two shell halves, a body portion and a cap portion. Other capsules comprising more than two parts are also possible. The capsule is typically a hollow shell of generally cylindrical shape having a diameter and length sufficient so that the caplet fits appropriately in the empty capsule. The clearance of the capsule shell and the caplet is preferably about + 0.5 mm. According to a specifically preferred embodiment of the present invention, the clearance of the capsule shell and the caplet is in the range of from about 0 to to about -0.5 mm, which means that the caplet is compressed in the capsule.
A specifically preferred process of the present invention is carried out as follows. Empty capsule shell parts are either kept after production at humid conditions in the range of from about 40 to about 90 %, particularly from about 60 to about 80 %, relative humidity to retain a moisture content of from about 16 to about 18 % by weight of the capsule shell or are re-humidified to said moisture content before feeding into a capsule filling machine.
The first capsule shell part is then kept under humid conditions within the filling machine at said moisture content during rectifying and assembling with a caplet having a moisture content in the range of from about 0 to about 12 % by weight.
A second or further capsule shell part is processed in the same matter as the first one. Finally, the encapsulated dosage form is dried at a relative humidity in the range of from about 20 to about 40 % and a temperature in the range of from about 15 to about 60 C, preferably from about 15 to about 40 C, more preferably from about 18 to about 25 C.
Caplets having a low moisture content of in the range of from about 0 to about 6 % by weight, or more preferably of from about 0 to about 3 % by weight, are especially suitable to be used in the process of the present invention. Conical ends of the caplet make the insertion of the caplet into one half of the capsule easier. After drying and shrinking the capsule parts together, the capsule can be further film coated, which coating may be enteric.
The capsule shell material can be a hydrophilic polymer, gelatin being the preferred choice. Other suitable capsule shell materials include starch, casein, chitosan, soya bean protein, safflower protein, alginates, gellan gum, carrageenan, xanthan gum, phtalated gelatin, succinated gelatin, cellulosephtalate-acetate, polyvinylacetate, hydroxypropyl methylcellulose, polyvinylacetate-phtalate, polymerisates of acrylic or mthacrylic esters or mixtures thereof. The capsule shell material may furthermore contain from about 0 to about 40 % pharmaceutically acceptable plasticizers based upon the weight of the hydrophilic polymer. The plasticizer which may be employed can be selected from polyethylene glycol, glycerol, sorbitol, dioctyl-sodium sulfosuccinate, triethyl citrate, tributyl citrate, 1,2-propyleneglycol, mono-, di, or tri-acetates of glycerol or mixtures thereof.
Additionally, the capsule shell material may contain pharmaceutically acceptable lubricants in the range of from about 0 to about 10% based upon the weight of the hydrophilic polymer. The lubricant may be selected from aluminiumstearate, calciumstearate, magnesiumstearate, tinstearate, talc, sodium lauryl sulfate, lecithins, mineral oils, stearic acid or silicones or mixtures thereof.
Moreover, the capsule shell material may contain pharmaceutically acceptable coloring agents in the range of from about 0 to about 10 % based upon the weight of the hydrophilic polymer. The coloring agent may be selected from azo-quinophthalone-, triphenylmethane- , xanthene-dyes, iron oxides or hydroxides, titanium dioxide or natural dyes or mixtures thereof. Further suitable coloring agents are sunset yellow, allura red, amaranth, cochineal red, azogeranine, tartrazine, brilliant black, canthaxanthin, patent blue, fast green, brilliant blue, acid green, erythrosine, q inoline yellow, indigotine, curcumin or carbon black.
Furthermore, the capsule shell material may contain pharmaceutically acceptable extenders in the range of from about 0 to about 95 % based upon the weight of the hydrophilic polymer. The extender may be selected from sunflower proteins, soybean proteins, cotton seed proteins, peanut proteins, rape seed proteins, lactose, gum arabic, acrylates or methacrylates, cellulose acetyl phthalates, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulosephthalate, hydroxymethylcellulose, polyvinylpyrrolidone, shellac, bentonite, polyvinyl-acetatephtalate, phthalated gelatin, succinated gelatin, agar agar, hydroxyalkylstarches or mixtures thereof.
The solid pharmaceutical dosage form according to the present invention also may comprise a coating selected from cellacephate, polyvinyl acetate phthalate, methacrylic acid polymers, hypromellose phthalate, hydroxyalkyl methyl cellulose phthalates or mixtures thereof.
The capsule parts of the solid dosage form of the present invention may have the same or different lengths and/or the same or different color. In the contact area of the capsule parts, the solid dosage form may be banded or easily dividable. The caplet being contained in the capsule can have a preformed step or groove in the dividing position of the capsule. To furthermore improve the caplet which is contained in the capsule, the caplet can be coated with an acceptable coating for tablet processing. In some cases, uncoated caplets are, however, preferred. A better contact between the inner shells of the capsule parts and the caplets can be obtained by treating the inner shells and/or the surface of the caplet with an adhesive. A suitable technique to apply the adhesive is spraying same on the shells and caplets immediately before assembling same. Suitable adhesives are e.g. tackidex or an aqueous gelatin solution. The solid dosage form according to the present invention may, for example, comprise a pharmaceutically or agrochemically active composition. Furthermore comprised in the solid dosage form can, for example, be a foodstuff or a dyestuff composition. In case the solid dosage form of the present invention contains a pharmaceutical composition, the active substance of same can, for example, be selected from betamethason, thioctacid, sotalol, salbutamol, norfenefrin, silymarin, dihydergotamin, buflomedil, etofibrat, indometacin, oxazepam, acetyldigoxin, piroxicam, haloperidol, isosorbide mononitrate, amitriptylin, diclofenac, nifedipin, verapamil, pyritinol, nitrendipin, doxycyclin, bromhexin, methylprednisolon, clonidin, fenofibrat, allopurinol, pirenzepin, levothyroxin, tamoxifen, metildigoxin, o- (β-hydroxyethyl) -rutoside, propicillin, aciclovirmononitrat, paracetamol, naftidrofuryl, pentoxifyllin, propafenon, acebutolol, 1-thyroxin, tramadol, bromocriptin, loperamid, ketotifen, fenoterol, ca-dobelisat, propranolol, minocyclin, nicergolin, ambroxol, metoprolol, β-sitosterin, enalaprilhydrogenmaleate, bezafibrat, isosorbide dinitrate, gallopamil, xantinolnicotinat, digitoxin, flunitrazepam, bencyclan, dexapanthenol, pindolol, lorazepam, diltiazem, piracetam, phenoxymethylpenicillin, furosemid, bromazepam, flunarizin, erythromycin, metoclopramid, acemetacin, ranitidin, biperiden, metamizol, doxepin, dipotassium-chlorazepat, tetrazepam, estramustinphosphate, terbutalin, captopril, maprotilin, prazosin, atenolol, glibenclamid, cefaclor, etilefrin, cimetidin, theophyllin, hydromorphon, ibuprofen, primi on, clobazam, oxaceprol, medroxyprogesteron, flecainid, Mg-pyridoxal-5-phosphateglutaminate, hymechromon, etofyllinclofibrat, vincamin, cinnarizin, diazepam, ketoprofen, flupentixol, molsidomin, glibornurid, dimetinden, melperon, soquinolol, dihydrocodein, clomethiazol, clemastin, glisoxepid, kallidinogenase, oxyfedrin, baclofen, carboxymethylcystsin, thioridacin, betahistin, 1-tryptophan, myrtol, bromelaine, prenylamin, salazosulfapyridin, astemizol, sulpirid, benzerazid, dibenzepin, acetylsalicylic acid, miconazol, nystatin, ketoconazol, sodium picosulfate, colestyramin, gemfibrocil, rifampicin, fluorcortolon, mexiletin, amoxicillin, terfenadrin, mucopolysaccharidpolysulfuric acid, triazolam, mianserin, tiaprofensaure, amenziniummetilsulfate, mefloquin, probucol, quinidine, carbamazepin, Mg-1-aspartate, penbutolol, piretanid, amitriptylin, caproteron, sodium valproinate, mebeverin, bisacodyl, 5-amino-salicyclic acid, dihydralazin, magaldrat, phenprocoumon, amantadin, naproxen, carteolol, famotidin, methyldopa, auranofin, estriol, nadolol, levomepromazin, doxorubicin, medofenoxat, azathioprin, flutamid, norfloxacin, fendilin, prajmaliumbitartrate, aescin, acromycin, anipamil, benzocain, β-carotin, cloramphenicol, chlorodiazepoxid, chlormadinonacetat, clorothiazid, cinnarizin, clonazepam, codein, dexamethason, dicumarol, digoxin, drotaverin, gramicidin, griseofulvin, hexobarbital hydrochlorothiazide, hydrocortison, hydroflumethiazid, ketoproten, lonetil, medazepam, mefrusid, methandrostenolon, sulfaperin, nalidixic acid, nitrazepam, nitrofurantoin, estradiol, papaverin, phenacetin, phenobarbital, phenylbutazon, phenytoin, prednison, reserpin, spironolacton, streptomycin, sulfamethazin, sulfamethizol, sulfamethoxazol, sulfamethoxydiazin, sulfathiazol, sulfisoxazol, testosteron, tolazamid, tolbutamid, trimethoprim, tyrothricin or mixtures thereof.
The purpose of the above description is to illustrate some configurations and uses of the present invention, without implying any limitation. It will be apparent to those skilled in the art that various modifications and variations may be made in the process and product of the invention without departing from the spirit or scope of the invention.

Claims

We claim:
1. A process for encapsulation of caplets in a capsule, comprising the following steps:
a. providing empty first and second capsule shell parts, b. filling at least one of said capsule parts with one or more caplets c. putting said capsule parts together, and d. treating the combined capsule parts by cold shrinking.
2. The process according to claim 1 wherein the caplets comprise a compressed material.
3. The process according to claim 1 wherein the empty capsule parts are either kept after production at humid conditions in the range of from about 40 to about 90 % relative humidity to retain a moisture content in the range of from about 16 to to about 18 % by weight of the capsule shell or are re-humidified to said moisture content before feeding into a capsule filling machine, wherein the first capsule part is kept under humid conditions within the filling machine at said moisture content during rectifying and assembling with a caplet having a moisture content in the range of from about 0 to about 12 by weight, the second capsule part is processed in the same manner, and the encapsulated dosage form is dried at a relative humidity in the range of from about 20 to about 40 % and a temperature in the range of from about 15 to about 60 C.
4. The process according to claim 3, wherein the encapsulated dosage form is dried at a temperature in the range of from about 15 to about 60 C.
5. The process according to claim 4, wherein the encapsulated dosage form is dried at a temperature in the range of from about 18 to about 25 C.
6. The process according to claim 3, wherein the capsule parts are maintained at a relative humidity in the range of from about 60 to about 80 % during the steps of feeding into a capsule filling machine, rectifying and assembling.
7. The process according to claim 3, wherein the moisture content of the capsule parts is in the range of from about 16 to about 18 % by weight.
8. The process according to claim 3, wherein the moisture content of the caplet is in the range of from about 0 to about 6 % by weight.
9. The process according to claim 3, wherein the moisture content of the caplet is in the range of from about 0 to about 3 % by weight.
10. The process according to claim 3, wherein the caplet has conical ends.
11. The process according to claim 3, wherein the clearance between the capsule part and the caplet is in the range of from 0 to 0.5mm.
12. Process according to claim 11, wherein the clearance between the capsule part and the caplet is in the range of from about 0 to -0.5mm.
13. The process according to claim 3, wherein after drying and shrinking of the capsule parts the encapsulated dosage form is film-coated.
14. Process according to claim 13, wherein the coating is enteric.
15. A solid dosage form obtainable according to the process of claim 1.
16. A solid dosage form obtainable according to the process of claim 3.
17. A solid dosage form according to claim 6, wherein the capsule part material comprises a hydrophilic polymer.
18. A solid dosage form according to claim 6, wherein the capsule part material is selected from the group consisting essentially of gelatin, starch casein, chitosan, soya bean protein, safflower protein, alginates, gellan gum, carrageenan, xanthan gum, phtalated gelatin, succinated gelatin, cellulosephtalate-acetate, polyvinylacetate, hydroxypropyl methylcellulose, polyvinylacetate-phtalate, polymerisates of acrylic or methacrylic esters or mixtures thereof.
19. A solid dosage form according to claim 17, wherein the capsule part material contains pharmaceutically acceptable plasticizers in the range of from about 0 to about 40 % based upon the weight of the hydrophilic polymer.
20. A solid dosage form according to claim 19, wherein the plasticizer is selected from the group consisting essentially of polyethylene glycol, glycerol, sorbitol, dioctyl-sodium sulfosuccinate, triethyl citrate, tributyl citrate, 1,2-propyleneglycol, mono-, di- or tri-acetates of glycerol or mixtures thereof.
21. A solid dosage form according to claim 17, wherein the capsule part material contains pharmaceutically acceptable lubricants in the range of from about 0 to about 10 % based upon the weight of the hydrophilic polymer.
22. A solid dosage form according to claim 21, wherein the lubricant is selected from the group consisting essentially of aluminiumstearate, calciumstearate, magnesiumstearate, tinstearate, talc, sodium lauryl sulfate, lecithins, mineral oils, stearic acid or silicones or mixtures thereof.
23. A solid dosage form according to claim 17, wherein the capsule part material contains pharmaceutically acceptable coloring agents in the range of from about 0 to about 10 % based upon the weight of the hydrophilic polymer.
24. A solid dosage form according to claim 23, wherein the coloring agent is selected from the group consisting essentially of azo-, quinophthaione-, triphenylmethane-, xanthene-dyes, iron oxides or hydroxides, titanium dioxide or natural dyes or mixtures thereof.
25. A solid dosage form according to claim 23, wherein the coloring agent is selected from sunset yellow, allura red, amaranth, cochineal red, azogeranine, tartrazine, brilliant black, canthaxanthin, patent blue, fast green, brilliant blue, acid green, erythrosine, quinoline yellow, indigotine, curcumin or carbon black.
26. A solid dosage form according to claim 17, wherein the capsule part material contains pharmaceutically acceptable extenders in the range of from about 0 to about 95% based upon the weight of the hydrophilic polymer.
27. A solid dosage form according to claim 4, wherein the capsule part material contains an extender.
28. A solid dosage form according to claim 27, wherein the extender is selected from the group consisting essentially of sunflower proteins, soybean proteins, cotton seed proteins, peanut proteins, rape seed proteins, lactose, gum arabic, acrylates or methacrylates, cellulose acetyl phthalates, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulosephthalate, hydroxymethylcellulose, polyvinyl pyrrolidone, shellac, bentonite, polyvinyl-acetatephtalate, phthalated gelatin, succinated gelatin, agar agar, hydroxyalkylstarches or mixtures thereof.
29. A solid dosage form obtainable according to the process of claim 13.
30. A solid pharmaceutical dosage form obtainable according to the process of claim 14.
31. A solid pharmaceutical dosage form according to claim 13, comprising a coating selected from the group consisting essentially of cellacephate, polyvinyl acetate phthalate, methacrylic acid polymers, hypromellose phthalate, hydroxyalkyl methyl cellulose phthalates or mixtures thereof.
32. A solid dosage form according to claim 6, wherein the first and second capsule parts have the same or different lengths.
33. A solid dosage form according to claim 6, wherein the first and second capsule parts have the same or different colors.
34. A solid dosage form according to claim 6, wherein the solid dosage form is banded at the contact area of the capsule parts.
35. A solid dosage form according to claim 6, wherein the solid dosage form is easily dividable at the contact area of the capsule parts.
36. A solid dosage form according to claim 2, wherein the caplet contained in the capsule has a preformed step or groove so that the solid dosage form may be dividing into separate portions.
37. A solid dosage form according to claim 6, wherein the caplet contained in the capsule is uncoated or coated with an acceptable coating for tablet processing.
38. A process according to claim 1, wherein an adhesive is sprayed onto the surface of the caplet and/or onto the • inner surface of the capsule parts immediately before assembling.
39. A process according to claim 38, wherein the adhesive is tackidex or an aqueous gelatin solution.
40. A solid dosage form according to claim 15 comprising a pharmaceutically active composition.
41. A solid dosage form according to claim 15 comprising an agrochemically active composition.
42. A solid dosage form according to claim 15 comprising a foodstuff composition.
43. A solid dosage form according to claim 15 comprising a dyestuff composition.
44. A solid dosage form according to claim 40, wherein the caplet contained in the capsule is a pharmaceutical composition with an active substance selected from the group consisting essentially of betamethason, thioctacid, sotalol, salbutamol, norfenefrin, silymarin, dihydergotamin, buflomedil, etofibrat, indometacin, oxazepam, acetyldigoxin, piroxicam, haloperidol, isosorbide mononitrate, amitriptylin, diclofenac, nifedipin, verapamil, pyritinol, nitrendipin, doxycyclin, bromhexin, methylprednisolon, clonidin, fenofibrat, allopurinol, pirenzepin, levothyroxin, tamoxifen, metildigoxin, o- (β-hydroxyethyl) -rutoside, propicillin, aciclovirmononitrat, paracetamol, naftidrofuryl, pentoxifyllin, propafenon, acebutolol, 1-thyroxin, tramadol, bromocriptin, loperamid, ketotifen, fenoterol, ca-dobelisat, propranolol, minocyclin, nicergolin, ambroxol, metoprolol, β-sitosterin, enalaprilhydrogenmaleate, bezafibrat, isosorbide dinitrate, gallopamil, xantinolnicotinat, digitoxin, flunitrazepam, bencyclan, dexapanthenol, pindolol, lorazepam, diltiazem, piracetam, phenoxymethylpenicillin, furosemid, bromazepam, flunarizin, erythromycin, metoclopramid, acemetacin, ranitidin, biperiden, metamizol, doxepin, dipotassium-chlorazepat, tetrazepam, estramustinphosphate, terbutalin, captopril, maprotilin, prazosin, atenolol, glibenclamid, cefaclor, etilefrin, cimetidin, theophyllin, hydromorphon, ibuprofen, primidon, clobazam, oxaceprol, medroxyprogesteron, flecainid, Mg-pyridoxal-5-phosphateglutaminate, hymechromon, etofyllinclofibrat, vincamin, cinnarizin, diazepam, ketoprofen, flupentixol, molsidomin, glibornurid, dimetinden, melperon, soquinolol, dihydrocodein, clomethiazol, clemastin, glisoxepid, kallidinogenase, oxyfedrin, baclofen, carboxymethylcystsin, thioridacin, betahistin, 1-tryptophan, myrtol, bromelaine, prenylamin, salazosulfapyridin, astemizol, sulpirid, benzerazid, dibenzepin, acetylsalicylic acid, miconazol, nystatin, ketoconazol, sodium picosulfate, colestyramin, gemfibrocil, rifampicin, fluorcortolon, mexiletin, amoxicillin, terfenadrin, mucopolysaccharidpolysulfuric acid, triazolam, mianserin, tiaprofensaure, amenziniummetilsulfate, mefloquin, probucol, quinidine, carbamazepin, Mg-1-aspartate, penbutolol, piretanid, amitriptylin, caproteron, sodium valproinate, mebeverin, bisacodyl, 5-amino-salicyclic acid, dihydralazin, magaldrat, phenprocoumon, amantadin, naproxen, carteolol, famotidin, methyldopa, auranofin, estriol, nadolol, levomepromazin, doxorubicin, medofenoxat, azathioprin, flutamid, norfloxacin, fendilin, prajmaliumbitartrate, aescin, acromycin, anipamil, benzocain, β-carotin, cloramphenicol, chlorodiazepoxid, chlormadinonacetat, clorothiazid, cinnarizin, clonazepa , codein, dexamethason, dicumarol, digoxin, drotaverin, gramicidin, griseofulvin, hexobarbital hydrochlorothiazide, hydrocortison, hydroflumethiazid, ketoproten, lonetil, medazepam, mefrusid, methandrostenolon, sulfaperin, nalidixic acid, nitrazepam, nitrofurantoin, estradiol, papaverin, phenacetin, phenobarbital, phenylbutazon, phenytoin, prednison, reserpin, spironolacton, streptomycin, sulfamethazin, sulfamethizol, sulfamethoxazol, sulfamethoxydiazin, sulfathiazol, sulfisoxazol, testosteron, tolazamid, tolbutamid, trimethoprim, tyrothricin or mixtures thereof.
PCT/US1995/014651 1994-12-16 1995-11-09 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process WO1996018370A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CA002205553A CA2205553C (en) 1994-12-16 1995-11-09 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
MX9703773A MX9703773A (en) 1994-12-16 1995-11-09 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process.
JP51881996A JP3670016B2 (en) 1994-12-16 1995-11-09 Method for encapsulating a caplet in a capsule and solid dosage form obtainable by such method
DE69518006T DE69518006T2 (en) 1994-12-16 1995-11-09 METHOD FOR ENCLOSURE TABLETS IN A CAPSULE AND SOLID DOSAGE FORMS AVAILABLE BY THIS METHOD
DK95939890T DK0797424T3 (en) 1994-12-16 1995-11-09 Method for encapsulating caplets in a capsule and solid dosage forms which can be prepared by this method
AT95939890T ATE194486T1 (en) 1994-12-16 1995-11-09 METHOD FOR ENCAPSULATING TABLETS INTO A CAPSULE AND SOLID DOSAGE FORMS OBTAINABLE BY THIS METHOD
EP95939890A EP0797424B1 (en) 1994-12-16 1995-11-09 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
GR20000402180T GR3034491T3 (en) 1994-12-16 2000-09-26 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US35813794A 1994-12-16 1994-12-16
US08/358,137 1994-12-16

Publications (1)

Publication Number Publication Date
WO1996018370A1 true WO1996018370A1 (en) 1996-06-20

Family

ID=23408454

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/014651 WO1996018370A1 (en) 1994-12-16 1995-11-09 Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process

Country Status (14)

Country Link
US (1) US6080426A (en)
EP (1) EP0797424B1 (en)
JP (1) JP3670016B2 (en)
KR (1) KR100468335B1 (en)
CN (1) CN1132566C (en)
AT (1) ATE194486T1 (en)
CA (1) CA2205553C (en)
DE (1) DE69518006T2 (en)
DK (1) DK0797424T3 (en)
ES (1) ES2150017T3 (en)
GR (1) GR3034491T3 (en)
MX (1) MX9703773A (en)
PT (1) PT797424E (en)
WO (1) WO1996018370A1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997037629A1 (en) * 1996-04-05 1997-10-16 Warner-Lambert Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
US6080426A (en) * 1994-12-16 2000-06-27 Warner-Lamberg Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
EP1291021A2 (en) * 2001-07-02 2003-03-12 Altergon S.A. Pharmaceutical formulations for thyroid hormones
JP2007308713A (en) * 1996-12-17 2007-11-29 Warner-Lambert Co Llc Polymer film composition for capsule
US7531567B2 (en) 2001-05-28 2009-05-12 Serumwerk Bernburg Ag Use of a medicament containing an effector of the glutathione metabolism together with α-lipoic acid in kidney replacement therapy
CN102688212A (en) * 2012-05-29 2012-09-26 北京均大高科科技孵化器有限公司 Isosorbide mononitrate sustained release tablet and preparation method thereof
US11318101B2 (en) 2016-07-06 2022-05-03 Qualicaps Co., Ltd. Hard capsule having improved hardness, and method for manufacturing same

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6428809B1 (en) * 1999-08-18 2002-08-06 Microdose Technologies, Inc. Metering and packaging of controlled release medication
KR20040100835A (en) * 2001-02-15 2004-12-02 킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨 Stabilized pharmaceutical and thyroid hormone compositions and method of preparation
US6555581B1 (en) 2001-02-15 2003-04-29 Jones Pharma, Inc. Levothyroxine compositions and methods
US20030032675A1 (en) * 2001-02-15 2003-02-13 Franz G. Andrew Manufacture of thyroid hormone tablets having consistent active moiety amounts
US20030224047A1 (en) * 2001-02-15 2003-12-04 Franz G. Andrew Levothyroxine compositions and methods
AU4061702A (en) * 2001-05-15 2003-04-03 Mcneil-Ppc, Inc. Dip coating compositions containing starch or dextrin
US20030072731A1 (en) * 2001-05-15 2003-04-17 Cynthia Gulian Dip coating compositions containing starch or dextrin
US20030070584A1 (en) * 2001-05-15 2003-04-17 Cynthia Gulian Dip coating compositions containing cellulose ethers
WO2002098403A1 (en) * 2001-06-01 2002-12-12 Georgetown University Steroid hormone and non-steroidal anti-inflammatory drug combinations for inducing tumor cell apoptosis
US20030190349A1 (en) * 2001-08-10 2003-10-09 Franz G. Andrew Methods of stabilizing pharmaceutical compositions
US20030180353A1 (en) * 2001-08-10 2003-09-25 Franz G. Andrew Stabilized pharmaceutical compositions
US20030198671A1 (en) * 2001-08-10 2003-10-23 Franz G. Andrew Levothyroxine compositions having unique plasma AUC properties
US20030198667A1 (en) * 2001-08-10 2003-10-23 Franz Andrew G. Methods of producing dispersible pharmaceutical compositions
US20030198672A1 (en) * 2001-08-14 2003-10-23 Franz G. Andrew Levothyroxine compositions having unique triidothyronine plasma AUC properties
US20030199586A1 (en) * 2001-08-14 2003-10-23 Franz G. Andrew Unique levothyroxine aqueous materials
US20030203967A1 (en) * 2001-08-14 2003-10-30 Franz G. Andrew Levothyroxine compositions having unique Tmax properties
US20030199587A1 (en) * 2001-08-14 2003-10-23 Franz G. Andrew Levothyroxine compositions having unique Cmax properties
US20030195253A1 (en) * 2001-08-14 2003-10-16 Franz G. Andrew Unadsorbed levothyroxine pharmaceutical compositions, methods of making and methods of administration
US8309118B2 (en) * 2001-09-28 2012-11-13 Mcneil-Ppc, Inc. Film forming compositions containing sucralose
US20040146559A1 (en) * 2002-09-28 2004-07-29 Sowden Harry S. Dosage forms having an inner core and outer shell with different shapes
US20040253312A1 (en) 2001-09-28 2004-12-16 Sowden Harry S. Immediate release dosage form comprising shell having openings therein
US20030190350A1 (en) * 2001-10-29 2003-10-09 Franz G. Andrew Levothyroxine compositions having unique triiodothyronine Tmax properties
US20030166732A1 (en) * 2002-02-27 2003-09-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ambroxol for the treatment of painful conditions in the mouth and pharyngeal cavity
US6946156B2 (en) * 2002-05-15 2005-09-20 Mcneil-Ppc, Inc. Process for enrobing a core
US7169450B2 (en) 2002-05-15 2007-01-30 Mcneil-Ppc, Inc. Enrobed core
US7429619B2 (en) * 2002-08-02 2008-09-30 Mcneil Consumer Healthcare Polyacrylic film forming compositions
EP1396263A1 (en) * 2002-08-09 2004-03-10 Warner-Lambert Company Film coating for tablets and caplets
RU2005108576A (en) 2002-09-28 2005-09-20 МакНЕЙЛ-ППС, ИНК. (US) POLYMERIC COMPOSITION AND CONTAINING ITS MEDICINAL FORMS
US20050079213A1 (en) * 2003-06-06 2005-04-14 Unilab Pharmatech Ltd Pharmaceutical compositions
CA2533150C (en) * 2003-07-25 2013-03-12 Warner Chilcott Company, Inc. A doxycycline metal complex in a solid dosage form
EP1648425B1 (en) * 2003-07-30 2007-02-21 Merrion Research I Limited Process and Machine for the Automated Manufacture of Gastro-Retentive Capsules
US7879354B2 (en) * 2004-01-13 2011-02-01 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US8067029B2 (en) * 2004-01-13 2011-11-29 Mcneil-Ppc, Inc. Rapidly disintegrating gelatinous coated tablets
US20050202079A1 (en) * 2004-03-15 2005-09-15 Mylan Pharmaceuticals Inc. Novel orally administrable formulation of nitrofurantoin and a method for preparing said formulation
US20080102116A1 (en) * 2004-09-13 2008-05-01 Perrigo Company Quick Dissolve Medicament and Method of Manufacturing
WO2006078925A2 (en) * 2005-01-21 2006-07-27 Warner Chilcott Company, Inc. A tetracycline metal complex in a solid dosage form
US20060222699A1 (en) * 2005-03-29 2006-10-05 Jonathan Gilinski Flavored vegetarian cellulose capsule and methods for producing said capsule.
US20070072910A1 (en) * 2005-09-29 2007-03-29 Smith Michael L Compositions and methods for lowering plasma concentrations of low density lipoproteins in humans
KR20090009214A (en) * 2006-03-28 2009-01-22 맥네일-피피씨, 인코포레이티드 Non-homogenous dosage form coatings
US20100086591A1 (en) 2006-09-15 2010-04-08 Murachanian Dennis C Rapidly Disintegrating Dosage Form
US20100029788A1 (en) * 2006-09-29 2010-02-04 John Pelesko Wet edible pearlescent film coatings
EP2099312B1 (en) * 2006-12-14 2016-05-04 Sensient Colors LLC Pearlescent pigment compositions and methods for making and using the same
US20100172991A1 (en) * 2007-06-08 2010-07-08 Henry Joseph Horacek Extended Release Formulation and Methods of Treating Adrenergic Dysregulation
US20090087490A1 (en) * 2007-06-08 2009-04-02 Addrenex Pharmaceuticals, Inc. Extended release formulation and method of treating adrenergic dysregulation
US20100092548A1 (en) * 2008-08-28 2010-04-15 Viva Pharmaceuticals Inc. Chewable softgel capsules
CN102300571A (en) * 2008-12-01 2011-12-28 英沃兹科医疗有限公司 Compositions Comprising Renin-angiotensin Aldosterone System Inhibitors And Lipoic Acid Compounds, And The Use Thereof For The Treatment Of Renin-angiotensin Aldosterone System Related Disorders
BR112013003762A2 (en) 2010-08-18 2016-05-31 Mcneil Ppc Inc tablet shell to enhance performance
US9119793B1 (en) 2011-06-28 2015-09-01 Medicis Pharmaceutical Corporation Gastroretentive dosage forms for doxycycline
US20140141075A1 (en) 2012-11-21 2014-05-22 Warner Chilcott Company, Llc 5-aminosalicylic acid capsule formulation
US10842802B2 (en) 2013-03-15 2020-11-24 Medicis Pharmaceutical Corporation Controlled release pharmaceutical dosage forms
CN103461336B (en) * 2013-09-26 2015-08-05 卞佳林 A kind of pleocidin and griseofulvin composite microcapsule insecticide
CN103461335B (en) * 2013-09-26 2015-08-05 卞佳林 A kind of pleocidin and griseofulvin composite microcapsule method for producing insecticide
EP3167870B1 (en) 2015-11-16 2024-01-03 Capsugel Belgium NV Tamperproof oral dosage form
EP3167869A1 (en) 2015-11-16 2017-05-17 Capsugel Belgium NV Tamperproof oral dosage form
RU2749902C2 (en) * 2018-10-31 2021-06-18 Общество С Ограниченной Ответственностью "Валента-Интеллект" Pharmaceutical composition for treatment of infectious and inflammatory diseases
CN110279890A (en) * 2019-04-15 2019-09-27 首都医科大学附属北京世纪坛医院 Method of modifying and application of the dexamethasone/minocycline based on liposome on the surface PEEK
EP3805577A1 (en) * 2019-10-11 2021-04-14 Hilti Aktiengesellschaft Threadlike package

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3258115A (en) * 1965-05-12 1966-06-28 Scherer Corp R P Two-piece hard gelatin capsule
DE2428397B2 (en) * 1974-06-12 1977-09-15 Scherer Hartkapsel Gmbh, 6930 Eberbach TWO-PIECE CAPSULE MADE OF HARD GELATINE
GB2149377A (en) * 1983-08-26 1985-06-12 Cosden Technology Forming tamper-resistant tamper-indicative capsules
EP0225565A2 (en) * 1985-12-06 1987-06-16 Boehringer Ingelheim Kg Divisible capsule
EP0435726A2 (en) * 1989-12-29 1991-07-03 Bristol-Myers Squibb Company Capsule and caplet combination

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US599865A (en) * 1898-03-01 Emanuel l
US724436A (en) * 1902-07-15 1903-04-07 Ernest C Clark Pill-coating machine.
US1520940A (en) * 1922-03-01 1924-12-30 Dulitz August Adolf Process for the manufacture of sealing caps and for applying them onto the vessels to be sealed
US1685392A (en) * 1925-08-12 1928-09-25 Cellacote Company Inc Preservative package and process of making the same
US1657982A (en) * 1926-02-15 1928-01-31 Parke Davis & Co Process of manufacturing gelatin capsules for use as bottle caps
US1774258A (en) * 1929-07-08 1930-08-26 Raymond A English Duplex capsule or the like
US1872190A (en) * 1930-06-07 1932-08-16 Sindl Otto Capsuling machine
US1931765A (en) * 1932-05-09 1933-10-24 Basil E Leever Beverage capsule
US2663130A (en) * 1946-12-26 1953-12-22 American Cyanamid Co Apparatus for producing symmetrical generally ellipsoidal capsules
US3045641A (en) * 1959-04-13 1962-07-24 Pfizer & Co C Apparatus for color-coding tablets
US3228789A (en) * 1962-10-22 1966-01-11 Jacob A Glassman Peroral capsules and tablets and the method for making same
US3185626A (en) * 1963-03-06 1965-05-25 Sterling Drug Inc Tablet coating method
DE2010987C3 (en) * 1970-03-09 1979-03-15 Ibm Deutschland Gmbh, 7000 Stuttgart Method for "making thin film magnetic heads having magnetic anisotropy
US3886940A (en) * 1970-07-10 1975-06-03 Squibb & Sons Inc Capsule
US3896762A (en) * 1973-12-07 1975-07-29 Purdue Research Foundation Coating apparatus
US3983258A (en) * 1975-02-07 1976-09-28 Continental Can Company, Inc. Process of packaging edible products containing exposed bones
US4562024A (en) * 1982-07-06 1985-12-31 Sterling Drug Inc. Process for preparing granulate containing poorly compressible medicinally active matter
JPS59131355A (en) * 1983-01-17 1984-07-28 森下仁丹株式会社 Multiple soft capsule
US4851230A (en) * 1983-04-07 1989-07-25 Bristol-Myers Company Capsule shaped tablets
US4591500A (en) * 1983-04-25 1986-05-27 Microencapsulation S.A. Tablet having the shape of a capsule, process and device for its preparation
US4684516A (en) * 1983-08-01 1987-08-04 Alra Laboratories, Inc. Sustained release tablets and method of making same
US4466844A (en) * 1983-09-19 1984-08-21 Cosden Technology, Inc. Gripper for capsule welder
US4928840A (en) * 1986-02-25 1990-05-29 American Home Products Corporation Tamper proof encapsulated medicaments
EP0271627B1 (en) * 1986-10-20 1992-04-15 Paolo Maso Bander machine for drugs containing capsules
US5074426A (en) * 1986-11-13 1991-12-24 Warner-Lambert Company Dividable capsule
US4966771A (en) * 1987-02-20 1990-10-30 Mcneilab, Inc. Gelatin coated caplets and process for making same
US4990358A (en) * 1987-02-20 1991-02-05 Mcneilab, Inc. Method for double dipping gelatin coated caplets
US4820524A (en) * 1987-02-20 1989-04-11 Mcneilab, Inc. Gelatin coated caplets and process for making same
US4921108A (en) * 1987-02-20 1990-05-01 Mcneilab, Inc. Apparatus for gelatin coating caplets
US4867983A (en) * 1987-02-20 1989-09-19 Mcneilab, Inc. Method for double dipping gelating coated caplets
US4844906A (en) * 1987-03-25 1989-07-04 Kv Pharmaceutical Company Tamper evident pharmaceutical capsule
US4973480A (en) * 1987-03-25 1990-11-27 K.V. Pharmaceutical Co. Tamper evident pharmaceutical capsule
US4936074A (en) * 1988-11-17 1990-06-26 D. M. Graham Laboratories, Inc. Process for preparing solid encapsulated medicament
US4965089A (en) * 1989-04-10 1990-10-23 Sauter Manufacturing Corp. Method and apparatus for the gelatin coating of caplets
US5146730A (en) * 1989-09-20 1992-09-15 Banner Gelatin Products Corp. Film-enrobed unitary-core medicament and the like
US5456919A (en) * 1989-12-29 1995-10-10 Bristol-Myers Squibb Company Capsule and caplet combination
US5198227A (en) * 1990-01-22 1993-03-30 Mcneil-Ppc, Inc. Dual subcoated simulated capsule medicament
US5081822A (en) * 1990-02-01 1992-01-21 Warner-Lambert Company Automatic caplet filler
US5089270A (en) * 1990-05-15 1992-02-18 L. Perrigo Company Capsule-shaped tablet
US5213738A (en) * 1990-05-15 1993-05-25 L. Perrigo Company Method for making a capsule-shaped tablet
US5460824A (en) * 1990-06-27 1995-10-24 Warner-Lambert Company Method for the preparation of an encapsulated medicament
US5188688A (en) * 1990-07-20 1993-02-23 Minnesota Mining And Manufacturing Company Method of sealing a gelatin capsule
US5098715A (en) * 1990-12-20 1992-03-24 Burroughs Wellcome Co. Flavored film-coated tablet
US5114720A (en) * 1990-12-27 1992-05-19 American Cyanamid Company Gelatin coated tablets and method for producing same
US5317849A (en) * 1992-08-07 1994-06-07 Sauter Manufacturing Corporation Encapsulation equipment and method
US5415868A (en) * 1993-06-09 1995-05-16 L. Perrigo Company Caplets with gelatin cover and process for making same
EP0797424B1 (en) * 1994-12-16 2000-07-12 Warner-Lambert Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
GB0423515D0 (en) * 2004-10-22 2004-11-24 Phoenix Product Dev Ltd A container

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3258115A (en) * 1965-05-12 1966-06-28 Scherer Corp R P Two-piece hard gelatin capsule
DE2428397B2 (en) * 1974-06-12 1977-09-15 Scherer Hartkapsel Gmbh, 6930 Eberbach TWO-PIECE CAPSULE MADE OF HARD GELATINE
GB2149377A (en) * 1983-08-26 1985-06-12 Cosden Technology Forming tamper-resistant tamper-indicative capsules
EP0225565A2 (en) * 1985-12-06 1987-06-16 Boehringer Ingelheim Kg Divisible capsule
EP0435726A2 (en) * 1989-12-29 1991-07-03 Bristol-Myers Squibb Company Capsule and caplet combination

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6080426A (en) * 1994-12-16 2000-06-27 Warner-Lamberg Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
US6245350B1 (en) 1994-12-16 2001-06-12 Warner-Lambert Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
WO1997037629A1 (en) * 1996-04-05 1997-10-16 Warner-Lambert Company Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
JP2007308713A (en) * 1996-12-17 2007-11-29 Warner-Lambert Co Llc Polymer film composition for capsule
US7531567B2 (en) 2001-05-28 2009-05-12 Serumwerk Bernburg Ag Use of a medicament containing an effector of the glutathione metabolism together with α-lipoic acid in kidney replacement therapy
EP1291021A2 (en) * 2001-07-02 2003-03-12 Altergon S.A. Pharmaceutical formulations for thyroid hormones
EP1291021A3 (en) * 2001-07-02 2003-04-16 Altergon S.A. Pharmaceutical formulations for thyroid hormones
US7723390B2 (en) 2001-07-02 2010-05-25 Altergon S.A. Pharmaceutical formulations for thyroid hormones
CN102688212A (en) * 2012-05-29 2012-09-26 北京均大高科科技孵化器有限公司 Isosorbide mononitrate sustained release tablet and preparation method thereof
CN102688212B (en) * 2012-05-29 2013-08-07 北京均大高科科技孵化器有限公司 Isosorbide mononitrate sustained release tablet and preparation method thereof
US11318101B2 (en) 2016-07-06 2022-05-03 Qualicaps Co., Ltd. Hard capsule having improved hardness, and method for manufacturing same

Also Published As

Publication number Publication date
ATE194486T1 (en) 2000-07-15
JP3670016B2 (en) 2005-07-13
KR980700050A (en) 1998-03-30
CA2205553A1 (en) 1996-06-20
EP0797424A1 (en) 1997-10-01
CN1170346A (en) 1998-01-14
DE69518006D1 (en) 2000-08-17
KR100468335B1 (en) 2005-09-02
EP0797424B1 (en) 2000-07-12
PT797424E (en) 2000-10-31
ES2150017T3 (en) 2000-11-16
DE69518006T2 (en) 2000-12-21
JPH11500326A (en) 1999-01-12
CN1132566C (en) 2003-12-31
DK0797424T3 (en) 2000-10-23
MX9703773A (en) 1997-08-30
CA2205553C (en) 2009-04-07
US6080426A (en) 2000-06-27
GR3034491T3 (en) 2000-12-29

Similar Documents

Publication Publication Date Title
EP0797424B1 (en) Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
EP0891180B1 (en) Process for encapsulation of caplets in a capsule
US5456919A (en) Capsule and caplet combination
CN103068375B (en) Tablet sleeve for improved performance
Srividya et al. Capsules and it’s technology: An Overview
EP0435726B1 (en) Capsule and caplet combination
US8293159B2 (en) Method and apparatus for manufacturing filled linkers
CA2214923C (en) Process for encapsulation of caplets in a capsule and solid dosage forms obtainable by such process
KR100463356B1 (en) Process for Encapsulation of Caplets in a Capsule and Solid Dosage Forms Obtainable by Such Process
US20200038294A1 (en) Tamperproof oral dosage form
MXPA98007667A (en) Process for the encapsulation of caps in a capsule and solid dose forms that can be obtained by such proc
EP2066307B1 (en) Rapidly disintegrating dosage form
EP3167870B1 (en) Tamperproof oral dosage form
TH21191B (en) A process for encapsulating caplets in capsules and solid size variations obtained by such processes.
TH24389A (en) A process for encapsulating caplets in capsules and solid size variations obtained by such processes.
WO2017136903A2 (en) Capsule for two incompatible drugs
WO2019113653A1 (en) Two-compartment capsule for drugs

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 95196811.4

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): CA CN JP KR MX

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2205553

Country of ref document: CA

Ref document number: 2205553

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1019970704011

Country of ref document: KR

ENP Entry into the national phase

Ref document number: 1996 518819

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1995939890

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1995939890

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1019970704011

Country of ref document: KR

WWG Wipo information: grant in national office

Ref document number: 1995939890

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1019970704011

Country of ref document: KR