WO1989008448A1 - Enteric coated spheroidal granules - Google Patents

Enteric coated spheroidal granules Download PDF

Info

Publication number
WO1989008448A1
WO1989008448A1 PCT/EP1989/000251 EP8900251W WO8908448A1 WO 1989008448 A1 WO1989008448 A1 WO 1989008448A1 EP 8900251 W EP8900251 W EP 8900251W WO 8908448 A1 WO8908448 A1 WO 8908448A1
Authority
WO
WIPO (PCT)
Prior art keywords
granules
enteric coated
coated granules
coating
aqueous medium
Prior art date
Application number
PCT/EP1989/000251
Other languages
French (fr)
Inventor
Olav Nicolai Gamst
Ole Christian Whist
Original Assignee
Nycomed As
Holmes, Michael, John
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 Nycomed As, Holmes, Michael, John filed Critical Nycomed As
Publication of WO1989008448A1 publication Critical patent/WO1989008448A1/en

Links

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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • the present invention relates to coated granules of spheroidal shape with optimised performance.
  • enteric coating as a method to bypass the gastric environment is well known.
  • the rationale for the pharmaceutical use of such formulations has been either to protect the gastric mucosa from local damage caused by the drug or to protect the drug from possible decomposition by the gastric fluid.
  • a typical example of a drug which may cause local damage of the gastric mucosa is aspirin. It has been shown, however, that similar mucosal damage is caused by other non-steroidal anti-inflammatory drugs such as naproxen and ketoprofen.
  • enteric coated tablets A potential drawback with the use of enteric coated tablets is related to the variations in the delay between administration and gastric emptying, which are dependent on whether the tablet is taken together with food or not.
  • Non- disintegrating single unit dose forms remain in the stomach until the end of the digestion phase and are only then cleared from the stomach and through the terminal ileu by the migrating myoelectric complex.
  • the onset of the effect of the drug is often unpredictable.
  • enteric coated granules have been introduced. Such granules of less than 2mm diameter are delivered through the pylorus together with food. Conventionally produced core granules are normally of different shape and size, including some hard-edged shapes, and this makes it difficult to provide an even coating. As a result, more coating material is needed to provide the required resistance against the gastric fluid. Normally, a release of up to 5% of the active material occurs after two hours in artificial gastric fluid at pH 1, even with a relatively " heavy coating. With such preparations, it is difficult to obtain complete protection of the gastric mucosa.
  • the present invention is based on the concept that the core granules should be of much more even size distribution and more precisely spheroidal shape, thus enabling the enteric coating to be of more uniform thickness.
  • the core granules should be of much more even size distribution and more precisely spheroidal shape, thus enabling the enteric coating to be of more uniform thickness.
  • enteric coated granules in which the core granules comprising an active substance are substantially all essentially spheroidal, with mean variations between maximum and minimum diameters less than 10% of the maximum diameter, the coated granules showing variations in maximum diameter not greater than 15%, the mean value of said maximum diameters being between 0.5 and 2.0mm, preferably between 0.5 and 1.5mm, said granules dissolving in an aqueous medium only at a pH of 5.5 or higher.
  • coated granules according to the invention have given specially good results in terms of resistance to gastric dissolution, e.g. at pH 1, and rapid dissolution in the gut, e.g. at pH 7.5 (see Tables I and III hereinafter).
  • enteric coated granules which release not more than 0.5% by weight of active substance after two hours in an aqueous medium at pH 1.0 and which release more than 50% by weight of the active substance after 50 minutes in an aqueous medium at pH 7.5, preferably more than 50% by weight after 45 minutes in such a medium.
  • the basal gastric pH can be surprisingly high.
  • individuals neutral values have been measured in fasting conditions.
  • the gastric content has a pH value between 1-3 and a transient rise to about 5 after a meal.
  • the gastric-resistant coating of potentially irritant drugs such as NSAIDs ought to resist transient rises in pH in order to prevent drug leakage in the stomach.
  • the granules may be coated with selected coating materials which dissolve at pH 6 or higher. Coating materials dissolving at pH 6.5 or greater are even more preferred.
  • Table III hereinafter shows the formulae of coating liquids where various anionic polymers of methacrylic acid and methacrylic acid methyl ester (Eudragit L, S and mixtures of L and S) have been used.
  • Eudragit L (50% methacrylic acid) dissolves at pH 6 or higher and Eudragit S (30% methacrylic acid) dissolves at pH 7.
  • Eudragit 30D is a copolymer of 50% methacrylic acid and 50% acrylic acid methyl ester which dissolves at pH 5.5.
  • Table III and Figure 1 hereinafter show the dissolution profiles of naproxen granules coated with the above Eudragit combinations, presented in Table II.
  • the invention is of particular use in the formulation of non-steroidal anti-inflammatory drugs (NSAID) having an adverse action on the gastric mucosa, for example diclofenac, ketoprofen, ibuprofen piroxicam or, more particularly, naproxen.
  • NSAID non-steroidal anti-inflammatory drugs
  • the granules according to the invention may be produced by subjecting an appropriate formulation of the active drug, for example an admixture with a diluent or excipient such as lactose, to granulation and spheroid formation, e.g. using an extruder combined with a spheronizer, or rotor granulator technology, to form the required spheroids.
  • Spheroidal granules so produced are rigorously examined and graded to retain only those which fall within the above limits, using appropriate sieves and microscopic sampling to determine spheroidal shape.
  • the graded spheroidal granules are coated, for example in a fluid bed coater, e.g.
  • the mean coating thickness is preferably in the range 20 to 25 microns.
  • the ingredients were premixed and 200ml of deionised water was added. After 5 minutes of mixing, the moist mass was granulated through an extruder and than processed to spheroidal granules in a spheronizer. Only those granules were retained which were within the size limits 1.0 to 1.4mm and which, on sampling, had a mean variation in maximum diameter not greater than 15% and variations between maximum and minimum diameter of about 7%.
  • Coating compositions according to Table II hereinafter were applied to the spheroidal granules of stage (a) .
  • the spheroidal granules were coated with the above dispersions in a fluid bed coating apparatus (wherein the particles were suspended in an upward vertical air flow during the coating procedure) to give uniformly coated granules having a mean calculated coating thickness of 20 microns.
  • the naproxen in the above formulations may be replaced by piroxicam, or other NSAIDs.
  • the granules according to the invention are preferably presented in gelatine capsules, which rapidly dissolve in the stomach.
  • the granules may alternatively be presented mixed with suitable excipients to form dispersions.

Abstract

Spheroidal granules having a high degree of uniformity are coated with an enteric coating dissolving in an aqueous medium only at a pH of 5.5 or above. The resulting granules give very low release of active substance in gastric fluid, thus avoiding damage to the gastric mucosa when the active substance is, for example, naproxen.

Description

"ENTERIC COATED SPHEROIDAL GRANULES"
The present invention relates to coated granules of spheroidal shape with optimised performance.
The use of enteric coating as a method to bypass the gastric environment is well known. The rationale for the pharmaceutical use of such formulations has been either to protect the gastric mucosa from local damage caused by the drug or to protect the drug from possible decomposition by the gastric fluid. A typical example of a drug which may cause local damage of the gastric mucosa is aspirin. It has been shown, however, that similar mucosal damage is caused by other non-steroidal anti-inflammatory drugs such as naproxen and ketoprofen.
A potential drawback with the use of enteric coated tablets is related to the variations in the delay between administration and gastric emptying, which are dependent on whether the tablet is taken together with food or not. Non- disintegrating single unit dose forms remain in the stomach until the end of the digestion phase and are only then cleared from the stomach and through the terminal ileu by the migrating myoelectric complex. However, because of wide variations in the timing of gastric emptying, the onset of the effect of the drug is often unpredictable.
In order to overcome this disadvantage, enteric coated granules have been introduced. Such granules of less than 2mm diameter are delivered through the pylorus together with food. Conventionally produced core granules are normally of different shape and size, including some hard-edged shapes, and this makes it difficult to provide an even coating. As a result, more coating material is needed to provide the required resistance against the gastric fluid. Normally, a release of up to 5% of the active material occurs after two hours in artificial gastric fluid at pH 1, even with a relatively"heavy coating. With such preparations, it is difficult to obtain complete protection of the gastric mucosa.
The present invention is based on the concept that the core granules should be of much more even size distribution and more precisely spheroidal shape, thus enabling the enteric coating to be of more uniform thickness. By avoidance of thin spots on the coated granules, the release of active substance into the gastric fluid can be minimised and by the avoidance of thick spots, the overall amount of coating can be optimised.
According to the present invention, we provide enteric coated granules in which the core granules comprising an active substance are substantially all essentially spheroidal, with mean variations between maximum and minimum diameters less than 10% of the maximum diameter, the coated granules showing variations in maximum diameter not greater than 15%, the mean value of said maximum diameters being between 0.5 and 2.0mm, preferably between 0.5 and 1.5mm, said granules dissolving in an aqueous medium only at a pH of 5.5 or higher.
The coated granules according to the invention have given specially good results in terms of resistance to gastric dissolution, e.g. at pH 1, and rapid dissolution in the gut, e.g. at pH 7.5 (see Tables I and III hereinafter). According to a further aspect of the invention, therefore, we provide enteric coated granules which release not more than 0.5% by weight of active substance after two hours in an aqueous medium at pH 1.0 and which release more than 50% by weight of the active substance after 50 minutes in an aqueous medium at pH 7.5, preferably more than 50% by weight after 45 minutes in such a medium.
It has been shown that the basal gastric pH can be surprisingly high. In some, presupposed healthy, individuals neutral values have been measured in fasting conditions. Normally the gastric content has a pH value between 1-3 and a transient rise to about 5 after a meal.
The gastric-resistant coating of potentially irritant drugs such as NSAIDs ought to resist transient rises in pH in order to prevent drug leakage in the stomach.
As a further aspect of the present invention, and in order to obtain pharmaceutical products with improved properties, the granules may be coated with selected coating materials which dissolve at pH 6 or higher. Coating materials dissolving at pH 6.5 or greater are even more preferred.
Table III hereinafter shows the formulae of coating liquids where various anionic polymers of methacrylic acid and methacrylic acid methyl ester (Eudragit L, S and mixtures of L and S) have been used. Eudragit L (50% methacrylic acid) dissolves at pH 6 or higher and Eudragit S (30% methacrylic acid) dissolves at pH 7. By using combinations of Eudragit L and S, coatings which start to dissolve between pH 6 and 7 can be produced. Eudragit 30D is a copolymer of 50% methacrylic acid and 50% acrylic acid methyl ester which dissolves at pH 5.5.
Table III and Figure 1 hereinafter show the dissolution profiles of naproxen granules coated with the above Eudragit combinations, presented in Table II.
The invention is of particular use in the formulation of non-steroidal anti-inflammatory drugs (NSAID) having an adverse action on the gastric mucosa, for example diclofenac, ketoprofen, ibuprofen piroxicam or, more particularly, naproxen.
The granules according to the invention may be produced by subjecting an appropriate formulation of the active drug, for example an admixture with a diluent or excipient such as lactose, to granulation and spheroid formation, e.g. using an extruder combined with a spheronizer, or rotor granulator technology, to form the required spheroids. Spheroidal granules so produced are rigorously examined and graded to retain only those which fall within the above limits, using appropriate sieves and microscopic sampling to determine spheroidal shape. The graded spheroidal granules are coated, for example in a fluid bed coater, e.g. with cellulose acetate phthalate or poly ethacrylate esters (Eudragit L, S or 30 D) containing small amounts of plasticizers such as polyols or organic esters, to give enteric coated granules of improved resistance against gastric fluid and with excellent rate of release in the small intestine (see Table I and Table III hereinafter) . The mean coating thickness is preferably in the range 20 to 25 microns. TABLE I
Dissolution rate of naproxen granules (1) , mean diameter 1.2mm, and piroxicam granules (2), mean diameter 1.05mm, coated with 7.5% "Eudragit L 30 D" (calculated as dry lacquer substance)
Figure imgf000007_0001
* Phosphate Buffer pH 6.8
The following Example is given by way of illustration only:
(a) Composition of naproxen spheroids:
Naproxen 500 g
Lactose 90 g
The ingredients were premixed and 200ml of deionised water was added. After 5 minutes of mixing, the moist mass was granulated through an extruder and than processed to spheroidal granules in a spheronizer. Only those granules were retained which were within the size limits 1.0 to 1.4mm and which, on sampling, had a mean variation in maximum diameter not greater than 15% and variations between maximum and minimum diameter of about 7%.
(b) Coating of naproxen spheroids:
Coating compositions according to Table II hereinafter were applied to the spheroidal granules of stage (a) .
The spheroidal granules were coated with the above dispersions in a fluid bed coating apparatus (wherein the particles were suspended in an upward vertical air flow during the coating procedure) to give uniformly coated granules having a mean calculated coating thickness of 20 microns.
The coated granules conformed to the following in vitro dissolution criteria:
2 hours at pH 1 not greater than 0.5%
50 minutes at pH 7.5 more than 50%
Further details are given in Table III hereinafter Table II : Formula of coating solution
Amounts of ingredients Example (% w/w) :
B D E
Eudragit L 30 D 15,0 (1)
Eudragit L 6,0 4,5 3,0
Eudragit S 1,5 3,0 6,0
Polyethylene glycol 400 1,5
Triacetin 1,5 1,5 1,5 1,5
Talc 3,5 2,8 2,8 2,8 2,8
Water 80,0
Ethanol 89,7 89,7 89,7 89,7
(1) Calculated as dry substance
Figure imgf000009_0001
Table III Gastric resistance, lag time and dissolution rate of Naproxen granules, mean diameter 1,2mm, coated with 10% of various Eudragit brands
Figure imgf000010_0001
Typical dissolution curves in phosphate buffer at pH 7.5 are given in Figure 1 (USP is United States Pharmacopeia) .
The naproxen in the above formulations may be replaced by piroxicam, or other NSAIDs.
The granules according to the invention are preferably presented in gelatine capsules, which rapidly dissolve in the stomach. The granules may alternatively be presented mixed with suitable excipients to form dispersions.

Claims

Claims
1. Enteric coated granules in which the core granules comprising an active substance are substantially all spheroidal, with mean variations between maximum and minimum diameters less than 10% of the maximum diameter, the coated granules showing variations in maximum diameter not greater than 15%, the mean value of said maximum diameters being between 0.5 and 2.0 mm, the granules dissolving in an aqueous medium only at a pH of 5.5 or higher.
2. Enteric coated granules as claimed in claim 1 wherein the mean value of the maximum diameters is between 0.5 and 1.5 mm.
3. Enteric coated granules as claimed in claim 1 or claim 2 wherein the granules dissolve in an aqueous medium only at a pH of 6 or higher.
4. Enteric coated granules as claimed in claim 3 wherein the granules dissolve in an aqueous medium only at a pH of 6.5 or higher.
5. Enteric coated granules as claimed in any preceding claim which release not more than 0.5% by weight of active substance after two hours in an aqueous medium at pH 1.0 and which release more than 50% by weight of active substance after 50 minutes in an aqueous medium at pH 7.5.
6. Enteric coated granules as claimed in any preceding claim wherein the coating comprises a mixture of polymers of methacrylic acid and esters thereof.
7. Enteric coated granules as claimed in claim 6 wherein the coating comprises a mixture of
(a) a polymer of methylmethacrylate containing 30% methacrylic acid and
(b) a polymer of methylmethacrylate containing 50% methacrylic acid.
8. Enteric coated granules as claimed in claim 7 in which the coating comprises components (a) and (b) in the ratio 1:3.
9. Enteric coated granules as claimed in claim 7 in which the coating comprises components (a) and (b) in the ratio 1:1.
10. Enteric coated granules as claimed in any preceding claim wherein the active substance is naproxen.
11. A process for the preparation of enteric coated granules as claimed in any preceding claim, comprising coating spheroidal granules as defined in claim 1 or claim 2 with an enteric coating.
PCT/EP1989/000251 1988-03-10 1989-03-09 Enteric coated spheroidal granules WO1989008448A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB888805695A GB8805695D0 (en) 1988-03-10 1988-03-10 Enteric coated spheroidal granules
GB8805695 1988-03-10

Publications (1)

Publication Number Publication Date
WO1989008448A1 true WO1989008448A1 (en) 1989-09-21

Family

ID=10633176

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1989/000251 WO1989008448A1 (en) 1988-03-10 1989-03-09 Enteric coated spheroidal granules

Country Status (3)

Country Link
AU (1) AU3218689A (en)
GB (1) GB8805695D0 (en)
WO (1) WO1989008448A1 (en)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0473431A1 (en) * 1990-08-30 1992-03-04 McNEIL-PPC, INC. Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets
US5260072A (en) * 1990-08-30 1993-11-09 Mcneil-Ppc, Inc. Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets
US5527545A (en) * 1989-09-18 1996-06-18 Recordati S.A. Chemical And Pharmaceutical Company Liquid-suspension controlled-release pharmaceutical composition
US5601845A (en) * 1991-08-12 1997-02-11 Euro-Celtique, S.A. Pharmaceutical spheroid formulation
WO2004041254A1 (en) * 2002-11-04 2004-05-21 Nycomed Danmark Aps Coating of a particulate material with an organic solvent-based coating composition
WO2004087113A1 (en) * 2003-04-04 2004-10-14 Ranbaxy Laboratories Limited Pharmaceutical compositions for colon specific delivery
US20160120819A1 (en) * 2014-10-31 2016-05-05 Purdue Pharma Methods and compositions particularly for treatment of attention deficit disorder
US10722473B2 (en) 2018-11-19 2020-07-28 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10751363B2 (en) 2015-03-23 2020-08-25 Algipharma As Use of aliginate oligomers and CFTR modulators in treatment of conditions associated with CFTR dysfunction
US11331349B2 (en) 2017-08-02 2022-05-17 Norges Miljo-Og Biovitenskapelige Universitet (Nmbu) Treatment or prevention of gastrointestinal dysbiosis
US11413306B2 (en) 2015-10-06 2022-08-16 Algipharma As Alginate oligomers for the treatment or prevention of microbial overgrowth in the intestinal tract

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU61380A1 (en) * 1969-07-28 1970-09-21
EP0080341A2 (en) * 1981-11-20 1983-06-01 A/S Alfred Benzon Pharmaceutical multiple-units formulation
EP0119480A2 (en) * 1983-02-23 1984-09-26 BASF Aktiengesellschaft Spherical monocrystals for pharmaceutical use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU61380A1 (en) * 1969-07-28 1970-09-21
EP0080341A2 (en) * 1981-11-20 1983-06-01 A/S Alfred Benzon Pharmaceutical multiple-units formulation
EP0119480A2 (en) * 1983-02-23 1984-09-26 BASF Aktiengesellschaft Spherical monocrystals for pharmaceutical use

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5527545A (en) * 1989-09-18 1996-06-18 Recordati S.A. Chemical And Pharmaceutical Company Liquid-suspension controlled-release pharmaceutical composition
EP0473431A1 (en) * 1990-08-30 1992-03-04 McNEIL-PPC, INC. Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets
US5260072A (en) * 1990-08-30 1993-11-09 Mcneil-Ppc, Inc. Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets
US5601845A (en) * 1991-08-12 1997-02-11 Euro-Celtique, S.A. Pharmaceutical spheroid formulation
US5670172A (en) * 1991-08-12 1997-09-23 Euro-Celtique, S.A. Pharmaceutical spheroid formulation
WO2004041254A1 (en) * 2002-11-04 2004-05-21 Nycomed Danmark Aps Coating of a particulate material with an organic solvent-based coating composition
WO2004087113A1 (en) * 2003-04-04 2004-10-14 Ranbaxy Laboratories Limited Pharmaceutical compositions for colon specific delivery
US10449159B2 (en) 2014-10-31 2019-10-22 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10512612B2 (en) 2014-10-31 2019-12-24 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10111839B2 (en) 2014-10-31 2018-10-30 Purdue Pharma Methods and compositions particularly for treatment of attention deficit disorder
US10292938B2 (en) 2014-10-31 2019-05-21 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10292939B2 (en) 2014-10-31 2019-05-21 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US20160120819A1 (en) * 2014-10-31 2016-05-05 Purdue Pharma Methods and compositions particularly for treatment of attention deficit disorder
US10500162B2 (en) 2014-10-31 2019-12-10 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10507186B2 (en) 2014-10-31 2019-12-17 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10512613B2 (en) 2014-10-31 2019-12-24 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US9974752B2 (en) 2014-10-31 2018-05-22 Purdue Pharma Methods and compositions particularly for treatment of attention deficit disorder
US10568841B2 (en) 2014-10-31 2020-02-25 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10688060B2 (en) 2014-10-31 2020-06-23 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US11896722B2 (en) 2014-10-31 2024-02-13 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder
US10751363B2 (en) 2015-03-23 2020-08-25 Algipharma As Use of aliginate oligomers and CFTR modulators in treatment of conditions associated with CFTR dysfunction
US11413306B2 (en) 2015-10-06 2022-08-16 Algipharma As Alginate oligomers for the treatment or prevention of microbial overgrowth in the intestinal tract
US11331349B2 (en) 2017-08-02 2022-05-17 Norges Miljo-Og Biovitenskapelige Universitet (Nmbu) Treatment or prevention of gastrointestinal dysbiosis
US11911418B2 (en) 2017-08-02 2024-02-27 Norges Miljo-Og Blovitenskapelige Universitet (NMBU) Treatment or prevention of gastrointestinal dysbiosis
US10722473B2 (en) 2018-11-19 2020-07-28 Purdue Pharma L.P. Methods and compositions particularly for treatment of attention deficit disorder

Also Published As

Publication number Publication date
AU3218689A (en) 1989-10-05
GB8805695D0 (en) 1988-04-07

Similar Documents

Publication Publication Date Title
US7018658B2 (en) Pharmaceutical pellets comprising tamsulosin
JP3902228B2 (en) Pharmaceutical dosage forms for colon delivery
EP0194838B1 (en) Controlled-release pharmaceutical formulation
US5149542A (en) Coating membrane and compositions prepared therefrom
JP3902229B2 (en) Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery
TW406022B (en) Method for producing slow-release granular agents
JP4436475B2 (en) Aqueous dispersions suitable for the production of binders or coatings for solid oral dosage forms, use of the aqueous dispersions and redispersible powders
JP4963767B2 (en) Controlled release formulation
EP0153104A2 (en) Diffusion coated multiple-units dosage form
JPH05201856A (en) Highly stable release control type medicine having acrylic polymer coating and making thereof
JPS60209518A (en) Storage-stable and quickly decomposable compression formed body containing pharmacological substance and manufacture
BG65398B1 (en) Enteric coated pharmaceutical composition and method of manufacturing it
MXPA04009378A (en) Pharmaceutical formulation for the active ingredient budesonide.
KR20010073172A (en) Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same
CA3069396A1 (en) Enteric hard capsule
WO1989008448A1 (en) Enteric coated spheroidal granules
Patil et al. Development and evaluation of a hot-melt coating technique for enteric coating
JPH08245422A (en) Thermoplastic coating and binder for medical form and peroral or percutaneous medical form containing this
US5492700A (en) Process and composition for the development of controlled release gemfibrozil dosage form
Wang et al. Formulation development of oral controlled-release pellets of diclofenac sodium
CN1232386A (en) Colonic delivery of weak acid drugs
JPS61176536A (en) Coated dosage form
GB2406517A (en) Controlled release micropellets of tetracyclines
US5358723A (en) Process and composition for the development of controlled release gemfibrozil dosage form
JPH057366B2 (en)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU DK FI GB JP NO US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE