AU601694B2 – Drug particles having constant release
– Google Patents
AU601694B2 – Drug particles having constant release
– Google Patents
Drug particles having constant release
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Publication number
AU601694B2
AU601694B2
AU61191/86A
AU6119186A
AU601694B2
AU 601694 B2
AU601694 B2
AU 601694B2
AU 61191/86 A
AU61191/86 A
AU 61191/86A
AU 6119186 A
AU6119186 A
AU 6119186A
AU 601694 B2
AU601694 B2
AU 601694B2
Authority
AU
Australia
Prior art keywords
coating
drug particles
core
particles according
ibuprofen
Prior art date
1985-08-16
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.)
Ceased
Application number
AU61191/86A
Other versions
AU6119186A
(en
Inventor
Barbara Ann Cappel
Richard Edward Keim
Scott Donald Whalen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
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.)
1985-08-16
Filing date
1986-08-15
Publication date
1990-09-20
1986-08-15
Application filed by Procter and Gamble Co
filed
Critical
Procter and Gamble Co
1987-02-19
Publication of AU6119186A
publication
Critical
patent/AU6119186A/en
1990-09-20
Application granted
granted
Critical
1990-09-20
Publication of AU601694B2
publication
Critical
patent/AU601694B2/en
2006-08-15
Anticipated expiration
legal-status
Critical
Status
Ceased
legal-status
Critical
Current
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Classifications
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K31/00—Medicinal preparations containing organic active ingredients
A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
A61K31/19—Carboxylic acids, e.g. valproic acid
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
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P25/00—Drugs for disorders of the nervous system
A61P25/04—Centrally acting analgesics, e.g. opioids
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Description
*1~ 601 9 4
AUSTRALIA
Patents Act COMPLETE SPECIFICATION
(ORIGINAL)
Class Int. Class Application Number: I’ t’ Lodged: Complete Specification Lodged: Accepted: Published: Priority This document confitains the ame-ndments made undcr Sctpnr 49 and is correct for printing.
liii 11 «J Related Art: o I 0 0 0 4 1 4 0 I 11 69 4.I< APPLICANT'S REF.: 3437 Name(s) of Applicant(s): The Procter Gamble Company S Address(es) of Applicant(s): One Procter Gamble Plaza Cincinnati, Ohio 45202, United States of America Actual Inventor(s): SCOTT DONALD WHALEN RICHARD EDWARD KEIM BARBARA ANN CAPPEL t f 1 t i Address for Service is: tilt t PHILLIPS, ORMONDE AND FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne, Australia, 3000 Complete Specification for the invention entitled: DRUG PARTICLES HAVING CONSTANT RELEASE The following statement is a full description of this invention, including the best method of performing it known to applicant(s): 2 1~ PI9/3/84 la DRUG PARTICLES HAVING CONSTANT RELEASE Scott Donald Whalen Richard Edward Keim Barbara Ann Cappel TECHNICAL FIELD The present invention is related to sustained release drug particles having a release profile providing for more constant release of the drug active.
BACKGROUND OF THE INVENTION This invention relates to pharmaceutical particles providing a prolonged release of the drug active.
The administration of drugs orally oftentimes presents serious problems. In very many cases, it is necessary for the drugs to be absorbed from the gastro-intestinal tract into the 15 bloodstream. When a drug is given by mouth, the assimilation is normally fairly rapid and the level in the blood reaches a maximum. Then it declines as the drug is excreted or otherwise removed from the bloodstream. The blood level falls and finally t C (C C reaches a level so low that it is no longer effective and it is then 20 necessary to take another dose. The peaks and valleys thus caused in blood level have several disadvantages. One is the necessity of taking frequent small doses in order to maintain a therapeutically desired blood level. This is awkward and ,presents a problem as the patient has to continue to take further doses. A second drawback is that in order to have a therapeutically useful blood level, each dose has to be fairly large so that after the blood level peak is reached and begins to subside, there will still remain sufficient of the drug to be useful. The necessity for large doses brings with it some problems. The large initial doses may be unacceptable or may produce some undesirable side reactions.
For the reasons set out above, various attempts have been made to slow up the release of drugs taken orally, producing a sustained release product. Sometimes it is felt desirable only to slow up the release sufficiently so that it extends over a long enough time to even out the more marked peaks and valleys in blood level. In other cases, it may be desirable to prevent C a
C
StI C I a aIaa i aI a rtt -2assimilation from the stomach but to permit assimilation from the intestine. Various coatings have been developed enteric coatings) to help achieve this purpose.
Some of the attempts at making improved sustained-release particles are reflected in patents issued in the area. One patent is 3,078,216, February 19, 1963 to Greif, which discloses sustained-release particles having a coating of water-insoluble wax and possibly, a second enteric coating. U.S. Patent 4,459,279, July 10, 1984 to Stricker et al., discloses drug granules having a coating of a water insoluble component and a water soluble component. As a final second coating an enteric polymer may be employed. European Patent Application 0 061 217, September 29, 1982 to Giudice et al., discloses drug particles having an inert core, a first layer of the drug and an outer second layer of polyvinyl pyrrolidone. European Patent Application 0 092 060.
October 26, 1983 to Colombo et al., discloses drug particles having an enteric polymer in the drug core, a first coating designed to regulate the release of the drug and a second coating to protect the first coating.
20 While the above described references disclose delayed release drug particles, they as well as other prior art executions, do not provide complete answers to making totally satisfactory delayed release products, particularly those containing propionic acid derivatives.
Some drugs, such as ibuprofen, do not appear to follow a pattern of constant release found for other drugs. Instead, the dissolution data for ibuprofen particles having a porous coating indicate that the controlling surface area is not the constant surface area of the porous coating, but the surface area of the ibuprofen particle which decreases with time as the drug dissolves. Thus, the dissolution rate decreases with time.
The decrease in dissolution rate with time of an ibuprofen particle having a porous coating can be compensated for if the resistance of the porous coating to diffusion also decreases with time. This can be achieved by decreasing its thickness with -3time. The present invention provides a means of producing a coating on an ibuprofen particle that decreases in thickness at a rate such that the decrease in surface area of the ibuprofen particle as it dissolves is compensated for and the dissolution rate remains essentially constant.
It is a further object of the present invention to provide an analgesic effective against a variety of pain, acute and chronic.
It is still a further object of the present invention to provide delayed release particles which are effective in the treatment of dysmenorrhea.
These and other objects will become readily apparent from the detailed description which follows.
As used herein all percentages and ratios are by weight unless otherwise specified.
SUMMARY OF INVENTION The present invention relates to therapeutic particles containing a drug active core, a first coating of a water soluble polymer, a second coating of an enteric material and a third coating of a material which is insoluble at any pH and acts as a diffusion barrier for the drug active.
DETAILED DESCRIPTION OF THE INVENTION The essential as well as optional components of the present particles are described below. In the present application the following terms have the meanings given.
"Pharmaceutically-acceptable" or "pharmacologically-acceptable", as used herein, means that the ingredients used in the compositions are suitable for use in contact with the tissue of humans, without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio.
The term "comprising", as used herein, means that various other compatible components, including both active and inert ingredients, can be conjointly employed in the compositions of this invention. The term "comprising" thus encompasses and includes the more restrictive terms "consisting of" and "consisting essentially of".
Y,
4 By "compatible" herein is meant that the components of the present invention are capable of being commingled without interacting in a manner which would substantially decrease the efficacy of the drug active under ordinary use conditions.
Drug Active The drug actives found useful in the particles of the present invention are propionic acid derivatives. Such compounds have both analgesic and anti-inflammatory activity and can be used at appropriate dosage levels in the present invention. The compounds are frequently used in their free acid form but also can be used in the form of their pharmaceutically accepted salts.
The propionic acid derivatives for use herein include, but are not limited to, ibuprofen, flurbiprofen, fenoprofen, ketoprofen, indoprofen, suprofen, and fluprofen. Structurally r, 15 related propionic acid derivatives having similar analgesic and anti-inflammatory properties are also intended to be encompassed by this group. Structural formulas for representative group members are set forth below: Propionic Acid Derivatives ibuprofen CH
(CH
3 2 C HCHO HCOOH flurbiprofen CHCOOH
CH
F-3 fenoprofen C CH S, i 3
CHCOOH
indoprofen O I 9 H3 I7C
