GB2170104A - Coated pharmaceutical dosage forms - Google Patents
Coated pharmaceutical dosage forms Download PDFInfo
- Publication number
- GB2170104A GB2170104A GB08601389A GB8601389A GB2170104A GB 2170104 A GB2170104 A GB 2170104A GB 08601389 A GB08601389 A GB 08601389A GB 8601389 A GB8601389 A GB 8601389A GB 2170104 A GB2170104 A GB 2170104A
- Authority
- GB
- United Kingdom
- Prior art keywords
- coating
- process according
- overcoat
- dosage forms
- coated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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
- A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
Coated pharmaceutical dosage forms comprises (1) a drug-containing substrate coated with a sustained release formulation, e.g. ethyl cellulose and (2) product of step (1) coated with a water-soluble overcoat, e.g. hydroxypropylmethycellulose or hydroxypropylcellulose. Substantial reductions in tackiness problems and curing times result when dosage forms are coated in this way.
Description
SPECIFICATION
Process for treating pharmaceutical dosage forms
Recently, owing to stringent government regulations and the safety hazards associated with the use of organic solvents in coating systems for dosage forms, emphasis has shifted from solvent-based to waterbased coating formulations. New polymeric dispersions have been developed and intensive research is being conducted to maximize the uses of water dispersible colloidai particles. However, these aqueous formulations have generally exhibited shortcomings during the coating process.
One major problem is the tackiness which occurs during the curing of polymeric coatings. Although elevated temperatures are required to drive off water rapidly and deposit a film on the product, usually moderate temperatures (300 - 50 ) are employed in order to avoid the tackiness that has been frequently observed. Once the product is coated, the deposited film requires treatment at lower temperatures for extended periods of time to fully coalesce the polymer beads and ensure a continuous film. If elevated temperatures are employed, coalescence time may be shortened and reproducible release profiles achieved. However, the film usually becomes tacky and makes product handling difficult.
According to the present invention, there is provided a process for treating a pharmaceutical dosage form, comprising the steps of:
(1) coating a drug-containing substrate with a sustained release formulation, and
(2) coating the product of step (1) with a water-soluble overcoat.
The present invention provides a process that substantially reduces or eliminates the tackiness problem, and significantly reduces the curing time for coatings from days down to minutes or hours. In accordance with the present invention, the product is first coated under suitable conditions using the appropriate sustained release formulation, followed, preferably immediately, by the provision of a watersoluble overcoat, for instance by spraying; thereafter the product temperature is elevated to the desired level. The process is continued until complete coalescence of the film is attained.
The optimum temperature and time to be used will depend upon the type of formulation, coating level and the type of polymeric dispersion. The overcoat is composed of a single agent or a combination containing one or more water-soluble, natural or synthetic polymers such a cellulosic derivatives, and polyethylene glycols. Pharmaceutically acceptable additives, such as talc or kaolin, may be added to the overcoat formulation to help reduce tackiness while the overcoat is applied.
In one preferred embodiment, drug pellets are coated with a sustained-release compositidn which contains ethyl cellulose, triethyl citrate, kaolin and water. The coated pellets are then heated to temperatures of the order of from 30"C to 70"C for a period of from 15 minutes to 3 hours.
An overcoat formulation containing hydroxypropyl methylcellulose, polyethylene glycol, talc and water is then applied to the pellets. The over-coated pellets do not exhibit the tackiness generally associated with coated dosage forms. The overcoat dries in from 5 to 10 minutes.
The process of the present invention can lead to several advantages over known processes of treating dosage forms. In addition to solving several handling problems, i.e. alleviating tackiness and slow curing, the process of the present invention can produce treated dosage forms whose release profiles are superior to those produced in accordance with known procedures.
Time and energy requirements can also be lessened when using the present invention. The coating process can be carried out using only one coating device, resulting in considerable savings.
The process of the present invention can include, as step (3), recovering the overcoated dosage form.
Substrates which can be coated in accordance with the inventive process encompass a wide variety of materials. While it is preferred that they contained one or more drugs as the principal active ingredients, other ingestible substances, e.g. vitamins, minerals, nutrients and the like, can be substituted for all or part of the drug(s) in the substrate.
Useful drugs include antihistamines, antihypertensives and tranquilizers. One preferred group of drugs to be treated includes antihistamines, such as diphenhydramine and pharmaceutically acceptable derivatives/precursors thereof. Diphenhydramine and diphenhydramine hydrochloride are highly preferred ingredients for inclusion in the drug-containing substrate. Other drugs whose taste or other characteristics dictate a need for delayed/sustained release, e.g. cholestyramine and procainamide and its salts, are operable.
The drug-containing substrate can also include one or more of a wide variety of additives conventionally employed in solid dosage forms, e.g. carriers, flavour enhancers, colourants, and the like. When such additives are employed, they are present in such quantities that the quantity of active ingredient, e.g.
drugs, which is present in the substrate is from about 5.0 to about 95.0 wt %, based on the total weight of the drug-containing substrate.
While the use of solid materials in the drug-containing substrate is preferred, the use of liquid ingredients, with or without suitable solid absorbents therefor, is also contemplated. The process of the invention is, with minor adjustment, suitable for treating liquid substrates.
The sustained release formulation
The first coating applied to the drug containing substrate is particularly formulated so that, after the dosage form is ingested, the drug or other active ingredient contained in the substrate is taken up by the body in a slow and sustained fashion. That is, the dosage release curves which result from the use of the
initial coating are smooth, almost linear, curves when cumulative percent release is plotted against time.
Suitable formulations for use in the initial coatings contain water soluble and/or water dispersible mat
rices to which suitable ingredients have been added in order to reduce the tackiness and curing time of the coated substrate.
Typical matrices are polymeric materials such as cellulosic ethers. Aquacoat, made by FMC, is an ex
ample of a highly preferred polymeric dispersion matrix. It is composed of ethylcellulose colloidal parti
cles dispersed in water with cetyl alcohol and sodium lauryl sulfate added as stabilizers. Mixtures of
matrices are operable.
Useful additives in the first coating include inert solids, e.g. clays and ion exchange materials which
modify the release of the active ingredient from the substrate through the coating. Talc and kaolin are
preferred.
Other additives, e.g. hydrophilic polymers such as polyethylene glycols can be employed. Triethyl cit
rate, a plasticizer, is a preferred processing aid. Mixtures of such additives are contemplated.
The relative quantities of the matrix material in the sustained release coating will be on the order of
about 50.0 to about 80.0 wt %, based in total coating solids weight. Other additives, if present, will com
bine about 50.0 to about 20.0 wt %, based on total solids.
Since the coating is to be applied from an aqueous vehicle, solvents and other non-aqueous ingredi
ents need not be used. The quantity of water present during the first coating operation depends upon
such factors as the nature of the substrate and the type of equipment employed for the coating opera
tion.
The hydrophilic overcoat
The second coating composition, or overcoat, is designed to enhance the processability of the final
product. It is the overcoat which significantly reduces the outlay in time and energy generally associated
with treating the coated dosage forms.
The overcoat or second coating of the invention, like the first or base coat, is applied from an aqueous
vehicle. The matrix of this second coating contains one or more hydrophilic, preferably highly water
soluble materials of monomeric or polymeric nature. One preferred matrix is hydroxypropylmethyl cellu
lose. Other suitable matrices include hydroxypropyl cellulose and the like. Mixtures are operable.
The use of hydrophilic matrices is preferred. However, non-hydrophilic matrices may be used in combi
nation with suitable amounts of fillers to yield properties similar to those attained using hydrophilic mat
rices. For instance, a water-insoluble hydrophilic polymer, e.g., an ethyi cellulose polymer containing
major amounts--i.e., 30-90% of talc, kaolin or other filler, will give similar results as a hydrophilic over
coat.
To assist in the flow properties of this coating when applied and in the subsequent handling of the
overcoated dosage form, conventional processing aids, e.g., surfactants, fillers, etc. can be employed.
One preferred group of surfactants are silicon polymers. Polyethylene glycols and other well-known hy
drophobic polymers are highly preferred as additives. Polyethylene glycol 3350 is particularly preferred
when aqueous hydroxypropylmethy cellulose is the matrix.
Any of the optional ingredients employable in the base coating, described above, can be employed in
the overcoat formulation. The amount of matrix material in the overcoat composition will range from
about 0.01 to about 100% wt % based on total solids weight.
Coating procedures
The two-step coating process carried out in accordance herewith can be effected using conventional
coating equipment. Suitable devices for applying the initial, or base, coating include fluidized bed granu
lation and drying devices and the like. The one preferred device is the Rotor Granulator made by Glatt.
In order to save time in the overall process, it is preferred that, following the initial coating step, the
base-coated substrate be allowed to sit, with optional heat treatment to temperatures of about 45"C to
about 70"C, and preferably about 55"C to about 60"C, to coaiesce the matrix particles, so that a useful film
results. When heat is employed it is generally used for about 15 to about 60 minutes, preferably about 20
to about 40 minutes.
The application of the second, or overcoat, formulation can be carried out using the same equipment
as was used for the base coat. One preferred embodiment requires the use of only one type of device
with continuous coating steps.
The drying temperatures and times to be used on the overcoat will be about 30 to about 80"C, for
about 2 to about 15 minutes. Generally, preferred temperatures and times are about 45 to about 60"C and about 5 to about 10 minutes, respectively. The drying parameters used in treating the based coating in
termediate--i.e., the product of step (1 )will be operable in this step as well.
Recovery of the final dosage form is carried out using conventional techniques. Once the overcoat has
dried, the treated dosage forms are processed via well-known operations, such as are generally em
ployed to accommodate packaging and/or storage requirements.
Other conventional techniques for handling oral dosage forms can be employed before, during and/or after the two-step process outlined above.
The chemical and physical nature of the substrate will dictate the final form which the preparations of this invention will take. For example, diphenydramine hydrochloride is a bitter-tasting solid substance.
Since it is in antihistamine, it is an excellent candidate for applicants' process.
While ingestible pellets are preferred final product, other coated dosage forms, e.g. powders, capsules
and the like, are also contemplated.
The following examples demonstrate the effectiveness of the invention.
Example I
The coating formulations used in this example were:
(a) Sustained-release (base) formulation
1. Aquacoat 465 gm
2. Triethylcitrate 186 gm
3. Kaolin 51 gm
4. Purified water 990 gm
(b) Overcoat formulation
5. Hydroxypropylmethylcellulose 6.0 gm
6. Polyethylene Glycol 3350 1.2 gm
7. Talc 1.0 gm
8. Purified water 91.8 gm
I. Sustained Release Coating: (Parameters for 5 kg of pellets)
Use 0.564 kg of coating dispersion for 1 kg of pellets.
A. Disperse 3 in 4 and hydrate for 10 minutes.
B. Add A and 2 to 1 (in that order) and mix for 10 minutes after each addition.
C. Place the drug pellets into Glatt Rotor-Granulator container (5 kg in Glatt Model GPCG-5).
D. Coat C with B using 1.2 mm nozzle orifice, atomizing pressure set at 2.5 bars, flap opening = 40%,
air inlet temperature = 45"C and bed temperature = 32-85"C, rotor = 250 rpm. Spray 8.0% of coating
suspension at the rate of 4.0 ml/minute per 1 kg pellets. Spray remainder of the coating suspension at
the rate of 10.0 ml/minute per 1 kg pellets.
II. Aqueous Overcoat:
Use 0.415 kg of coating dispersion for 1 kg of core pellets.
E. Add 6 to about 90% of 8, heat to 60"C and sprinkle in 5. Cool to room temperature with mixing.
Continue mixing until dissolved. Disperse 7; continue mixing throughout the coating process.
F. Coat pellets from I in Rotor-Granulator with E immediately after the sustained release coating using
a 1.2 mm nozzle orifice, atomizing pressure set at 2.5 bars, air inlet temperature = 65"C and bed temper
ature = 45-50"C. Spray at the rate of 24 ml/minute per 1 kg of pellets. Dry the coated pellets for 30 min
utes at an inlet air temperature of 70"C and rotor speed of 100 rpm.
The figure
The figure depicts the release profiles of diphenhydramine pellets, a portion of which were cured at 60 for one hour only using the claimed procedure (lower curve) and another portion which were further
stored at 60 for one more week in an oven (upper curve). The similarity of the curves underscores the
efficiency of Applicants' curing process.
Reasonable variations, such as those which would occur to a skilled artisan, can be made herein with
out departing from the scope of the invention.
Claims (10)
1. A process for treating a pharmaceutical dosage form, comprising the steps of:
(1) coating a drug-containing substrate with a sustained release formulation, and
(2) coating the product of step (1) with a water-soluble overcoat.
2. A process according to Claim 1, which also includes, as step (3), recovering the overcoated dosage form.
3. A process according to Claim 1 or 2, wherein the formulation employed in step (1) contains a
water-dispersible polymer and an adsorbent.
4. A process according to Claim 1, 2, or 3, wherein the overcoat contains a water-soluble polymer.
5. A process according to Claim 4, wherein the overcoat additionally includes at least one processing aid.
6. A process according to Claim 5, wherein the processing aid is selected form adsorbents, plasticiz
ers, and mixtures thereof.
7. A process according to any preceding claim, wherein the drug-containing substrate is a pellet.
8. A process according to any preceding claim, wherein the overcoat contains at least one hydrophoi bic polymer.
9. A process according to any preceding claim, wherein steps (1) and (2) are carried out in the same device without removal of the product of step (1) prior to commencement of step (2).
10. An overcoated dosage form produced by a process according to any preceding claim.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US69694585A | 1985-01-30 | 1985-01-30 | |
US06/696,955 US4600645A (en) | 1985-01-31 | 1985-01-31 | Process for treating dosage forms |
Publications (2)
Publication Number | Publication Date |
---|---|
GB8601389D0 GB8601389D0 (en) | 1986-02-26 |
GB2170104A true GB2170104A (en) | 1986-07-30 |
Family
ID=27105903
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08601389A Withdrawn GB2170104A (en) | 1985-01-30 | 1986-01-21 | Coated pharmaceutical dosage forms |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB2170104A (en) |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0207041A2 (en) * | 1985-06-12 | 1986-12-30 | "Galephar" | Pharmaceutical tablets for easy administration of pellets, their preparation and use |
EP0339811A2 (en) * | 1988-04-28 | 1989-11-02 | Alza Corporation | Aqueous based pharmaceutical coating composition for dosage forms |
WO1992009270A1 (en) * | 1990-11-22 | 1992-06-11 | British Technology Group Ltd | Controlled release compositions |
WO1992011845A1 (en) * | 1991-01-03 | 1992-07-23 | Glaxo Canada Inc. | Method for production of solid pharmaceutical preparation |
EP0548448A1 (en) * | 1991-12-24 | 1993-06-30 | Euro-Celtique S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5472712A (en) * | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
US5681585A (en) * | 1991-12-24 | 1997-10-28 | Euro-Celtique, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5683719A (en) * | 1990-11-22 | 1997-11-04 | British Technology Group Limited | Controlled release compositions |
US5958459A (en) * | 1991-12-24 | 1999-09-28 | Purdue Pharma L.P. | Opioid formulations having extended controlled released |
US6103261A (en) | 1993-07-01 | 2000-08-15 | Purdue Pharma Lp | Opioid formulations having extended controlled release |
US6306438B1 (en) | 1997-07-02 | 2001-10-23 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
US6733783B2 (en) | 2000-10-30 | 2004-05-11 | Euro-Celtique S.A. | Controlled release hydrocodone formulations |
US7740881B1 (en) | 1993-07-01 | 2010-06-22 | Purdue Pharma Lp | Method of treating humans with opioid formulations having extended controlled release |
US7846476B2 (en) | 2001-05-02 | 2010-12-07 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
US7883722B2 (en) | 1998-04-03 | 2011-02-08 | Egalet Ltd. | Controlled release composition |
US7943174B2 (en) | 1999-10-29 | 2011-05-17 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8298581B2 (en) | 2003-03-26 | 2012-10-30 | Egalet A/S | Matrix compositions for controlled delivery of drug substances |
US8449914B2 (en) | 2002-11-08 | 2013-05-28 | Egalet Ltd. | Controlled release carvedilol compositions |
US8609143B2 (en) | 2001-09-21 | 2013-12-17 | Egalet Ltd. | Morphine polymer release system |
US8617605B2 (en) | 2001-09-21 | 2013-12-31 | Egalet Ltd. | Polymer release system |
US8877241B2 (en) | 2003-03-26 | 2014-11-04 | Egalet Ltd. | Morphine controlled release system |
US9005660B2 (en) | 2009-02-06 | 2015-04-14 | Egalet Ltd. | Immediate release composition resistant to abuse by intake of alcohol |
US9023394B2 (en) | 2009-06-24 | 2015-05-05 | Egalet Ltd. | Formulations and methods for the controlled release of active drug substances |
US9044402B2 (en) | 2012-07-06 | 2015-06-02 | Egalet Ltd. | Abuse-deterrent pharmaceutical compositions for controlled release |
US9642809B2 (en) | 2007-06-04 | 2017-05-09 | Egalet Ltd. | Controlled release pharmaceutical compositions for prolonged effect |
US9655893B2 (en) | 2001-05-02 | 2017-05-23 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB931150A (en) * | 1958-12-22 | 1963-07-10 | Upjohn Co | A process for the two-fold encapsulation of hydrophilic material by phase separation |
GB1179938A (en) * | 1966-11-23 | 1970-02-04 | Merck & Co Inc | Medicinal Sustained-Release Tablets. |
EP0122077A2 (en) * | 1983-04-06 | 1984-10-17 | ELAN CORPORATION, Plc | Sustained absorption pharmaceutical composition |
EP0123470A1 (en) * | 1983-04-21 | 1984-10-31 | ELAN CORPORATION, Plc | Controlled absorption pharmaceutical composition |
-
1986
- 1986-01-21 GB GB08601389A patent/GB2170104A/en not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB931150A (en) * | 1958-12-22 | 1963-07-10 | Upjohn Co | A process for the two-fold encapsulation of hydrophilic material by phase separation |
GB1179938A (en) * | 1966-11-23 | 1970-02-04 | Merck & Co Inc | Medicinal Sustained-Release Tablets. |
EP0122077A2 (en) * | 1983-04-06 | 1984-10-17 | ELAN CORPORATION, Plc | Sustained absorption pharmaceutical composition |
EP0123470A1 (en) * | 1983-04-21 | 1984-10-31 | ELAN CORPORATION, Plc | Controlled absorption pharmaceutical composition |
Cited By (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0207041A3 (en) * | 1985-06-12 | 1988-03-16 | "Galephar" | Pharmaceutical tablets for easy administration of pellets, their preparation and use |
EP0207041A2 (en) * | 1985-06-12 | 1986-12-30 | "Galephar" | Pharmaceutical tablets for easy administration of pellets, their preparation and use |
EP0339811A2 (en) * | 1988-04-28 | 1989-11-02 | Alza Corporation | Aqueous based pharmaceutical coating composition for dosage forms |
EP0339811A3 (en) * | 1988-04-28 | 1990-11-07 | Alza Corporation | Aqueous based pharmaceutical coating composition for dosage forms |
US5683719A (en) * | 1990-11-22 | 1997-11-04 | British Technology Group Limited | Controlled release compositions |
WO1992009270A1 (en) * | 1990-11-22 | 1992-06-11 | British Technology Group Ltd | Controlled release compositions |
WO1992011845A1 (en) * | 1991-01-03 | 1992-07-23 | Glaxo Canada Inc. | Method for production of solid pharmaceutical preparation |
US5681585A (en) * | 1991-12-24 | 1997-10-28 | Euro-Celtique, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US6129933A (en) * | 1991-12-24 | 2000-10-10 | Purdue Pharma Lp | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
AU680491B2 (en) * | 1991-12-24 | 1997-07-31 | Euro-Celtique S.A. | Controlled release formulations coated with aqueous dispersions of ethyl cellulose |
US7316821B2 (en) | 1991-12-24 | 2008-01-08 | Purdue Pharma, L.P. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5273760A (en) * | 1991-12-24 | 1993-12-28 | Euroceltigue, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5958459A (en) * | 1991-12-24 | 1999-09-28 | Purdue Pharma L.P. | Opioid formulations having extended controlled released |
US6905709B2 (en) | 1991-12-24 | 2005-06-14 | Purdue Pharma, Lp | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5472712A (en) * | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
EP0548448A1 (en) * | 1991-12-24 | 1993-06-30 | Euro-Celtique S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US6143322A (en) | 1993-07-01 | 2000-11-07 | Purdue Pharma L.P. | Method of treating humans with opioid formulations having extended controlled release |
US6103261A (en) | 1993-07-01 | 2000-08-15 | Purdue Pharma Lp | Opioid formulations having extended controlled release |
US7740881B1 (en) | 1993-07-01 | 2010-06-22 | Purdue Pharma Lp | Method of treating humans with opioid formulations having extended controlled release |
US6306438B1 (en) | 1997-07-02 | 2001-10-23 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
US6645527B2 (en) | 1997-07-02 | 2003-11-11 | Euro-Celtique S.A. | Stabilized sustained release tramadol formulations |
US7883722B2 (en) | 1998-04-03 | 2011-02-08 | Egalet Ltd. | Controlled release composition |
US8980291B2 (en) | 1999-10-29 | 2015-03-17 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9675611B1 (en) | 1999-10-29 | 2017-06-13 | Purdue Pharma L.P. | Methods of providing analgesia |
US7943174B2 (en) | 1999-10-29 | 2011-05-17 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9320717B2 (en) | 1999-10-29 | 2016-04-26 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9278074B2 (en) | 1999-10-29 | 2016-03-08 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9056107B1 (en) | 1999-10-29 | 2015-06-16 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US10076516B2 (en) | 1999-10-29 | 2018-09-18 | Purdue Pharma L.P. | Methods of manufacturing oral dosage forms |
US9669022B2 (en) | 1999-10-29 | 2017-06-06 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8975273B2 (en) | 1999-10-29 | 2015-03-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9669024B2 (en) | 1999-10-29 | 2017-06-06 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US6733783B2 (en) | 2000-10-30 | 2004-05-11 | Euro-Celtique S.A. | Controlled release hydrocodone formulations |
US9056052B1 (en) | 2000-10-30 | 2015-06-16 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8647667B2 (en) | 2000-10-30 | 2014-02-11 | Purdue Pharma, L.P. | Controlled release hydrocodone formulations |
US9682077B2 (en) | 2000-10-30 | 2017-06-20 | Purdue Pharma L.P. | Methods of providing analgesia |
US8951555B1 (en) | 2000-10-30 | 2015-02-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US10022368B2 (en) | 2000-10-30 | 2018-07-17 | Purdue Pharma L.P. | Methods of manufacturing oral formulations |
US9517236B2 (en) | 2000-10-30 | 2016-12-13 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8551520B2 (en) | 2000-10-30 | 2013-10-08 | Purdue Pharma L.P. | Controlled release hydrocodone |
US9023401B1 (en) | 2000-10-30 | 2015-05-05 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9669023B2 (en) | 2000-10-30 | 2017-06-06 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9572804B2 (en) | 2000-10-30 | 2017-02-21 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8715721B2 (en) | 2000-10-30 | 2014-05-06 | Purdue Pharma L.P. | Controlled release hydrocodone |
US8361499B2 (en) | 2000-10-30 | 2013-01-29 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9060940B2 (en) | 2000-10-30 | 2015-06-23 | Purdue Pharma L.P. | Controlled release hydrocodone |
US9198863B2 (en) | 2000-10-30 | 2015-12-01 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9205055B2 (en) | 2000-10-30 | 2015-12-08 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9205056B2 (en) | 2000-10-30 | 2015-12-08 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8231898B2 (en) | 2000-10-30 | 2012-07-31 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9289391B2 (en) | 2000-10-30 | 2016-03-22 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8142811B2 (en) | 2000-10-30 | 2012-03-27 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9572805B2 (en) | 2000-10-30 | 2017-02-21 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9526724B2 (en) | 2000-10-30 | 2016-12-27 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9504681B2 (en) | 2000-10-30 | 2016-11-29 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9655893B2 (en) | 2001-05-02 | 2017-05-23 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
US10660886B2 (en) | 2001-05-02 | 2020-05-26 | Purdue Pharma L.P. | Oxycodone formulations |
US9750736B2 (en) | 2001-05-02 | 2017-09-05 | Purdue Pharma L.P. | Oxycodone formulations |
US7846476B2 (en) | 2001-05-02 | 2010-12-07 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
US8808745B2 (en) | 2001-09-21 | 2014-08-19 | Egalet Ltd. | Morphine polymer release system |
US8609143B2 (en) | 2001-09-21 | 2013-12-17 | Egalet Ltd. | Morphine polymer release system |
US9707179B2 (en) | 2001-09-21 | 2017-07-18 | Egalet Ltd. | Opioid polymer release system |
US9694080B2 (en) | 2001-09-21 | 2017-07-04 | Egalet Ltd. | Polymer release system |
US8617605B2 (en) | 2001-09-21 | 2013-12-31 | Egalet Ltd. | Polymer release system |
US8449914B2 (en) | 2002-11-08 | 2013-05-28 | Egalet Ltd. | Controlled release carvedilol compositions |
US8877241B2 (en) | 2003-03-26 | 2014-11-04 | Egalet Ltd. | Morphine controlled release system |
US9375428B2 (en) | 2003-03-26 | 2016-06-28 | Egalet Ltd. | Morphine controlled release system |
US9884029B2 (en) | 2003-03-26 | 2018-02-06 | Egalet Ltd. | Morphine controlled release system |
US8298581B2 (en) | 2003-03-26 | 2012-10-30 | Egalet A/S | Matrix compositions for controlled delivery of drug substances |
US9642809B2 (en) | 2007-06-04 | 2017-05-09 | Egalet Ltd. | Controlled release pharmaceutical compositions for prolonged effect |
US9005660B2 (en) | 2009-02-06 | 2015-04-14 | Egalet Ltd. | Immediate release composition resistant to abuse by intake of alcohol |
US9358295B2 (en) | 2009-02-06 | 2016-06-07 | Egalet Ltd. | Immediate release composition resistant to abuse by intake of alcohol |
US9023394B2 (en) | 2009-06-24 | 2015-05-05 | Egalet Ltd. | Formulations and methods for the controlled release of active drug substances |
US9044402B2 (en) | 2012-07-06 | 2015-06-02 | Egalet Ltd. | Abuse-deterrent pharmaceutical compositions for controlled release |
US9549899B2 (en) | 2012-07-06 | 2017-01-24 | Egalet Ltd. | Abuse deterrent pharmaceutical compositions for controlled release |
Also Published As
Publication number | Publication date |
---|---|
GB8601389D0 (en) | 1986-02-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4600645A (en) | Process for treating dosage forms | |
GB2170104A (en) | Coated pharmaceutical dosage forms | |
FI103475B (en) | Process for the preparation of a controlled release preparation | |
US5084287A (en) | Pharmaceutically useful micropellets with a drug-coated core and controlled-release polymeric coat | |
US6270805B1 (en) | Two pellet controlled release formulation for water soluble drugs which contains an alkaline metal stearate | |
US6149943A (en) | Microcrystalline cellulose particles having active core | |
EP0067539B1 (en) | Sustained release pharmaceutical composition | |
US6238705B1 (en) | Bioerodible porous compositions | |
US4433076A (en) | Coating agent for medicaments and methods for making and using the same | |
US5186930A (en) | Sustained release oral suspensions | |
EP1748764B1 (en) | An amine drug-containing slow-release granule preparation based on particles with a coating layer and the corresponding method of production | |
AU750617B2 (en) | Multiple unit controlled food effect-independent release pharmaceutical preparations and method for preparing the same | |
EP0648487A1 (en) | Dispersion of enteric coating agent | |
JPH0530804B2 (en) | ||
CZ180595A3 (en) | Enteric pellet containing duloxetin | |
JPH08502264A (en) | Novel composition for oral therapy of cognitive impairment and method therefor | |
US5026709A (en) | Method for the preparation of a theophylline sustained release pharmaceutical composition and the composition prepared thereby | |
US7829148B2 (en) | Coating process to produce controlled release coatings | |
JPH01311024A (en) | Drug preparation having controlled acting substance release properties containing azelastine and production thereof | |
EP0662323A1 (en) | Method for preparing aqueous emulsion for coating solid pharmaceutical preparations | |
GB2098867A (en) | Sustained release pharmaceutical composition | |
EP0352800A2 (en) | Aqueous polymeric dispersion of cellulosic and acrylic based polymers for preparing pharmaceutical dosage forms and dosage forms thereof | |
CA2321969C (en) | Process for the production of encased, spherical granular grains | |
GB2170210A (en) | Coating composition for dosage forms | |
HU186431B (en) | Process for preparing coated acetyl-salicilyc acid derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |