WO1984000004A1

WO1984000004A1 - Sustained release aspirin

Info

Publication number: WO1984000004A1
Application number: PCT/US1983/000928
Authority: WO
Inventors: Hsiao Charles
Original assignee: Key Pharma
Priority date: 1982-06-14
Filing date: 1983-06-14
Publication date: 1984-01-05
Also published as: EP0111560A4; EP0111560A1

Abstract

A sustained release aspirin dosage form permits the continuous delivery of aspiring into the gastrointestinal tract for a period of at least eight hours. The sustained release aspirin dosage form comprises a plurality of polymerically coated aspirin crystals each of which comprises an aspirin seed. The majority of aspirin seeds have a mesh size of from about 30 to about 60 mesh. Each of the aspirin seeds is individually coated with a polymeric mixture, which comprises from about 1.5 to about 15 parts by weight ethylcellulose and about one part by weight hydroxypropylcellulose.

Description

SUSTAINED RELEASE ASPIRIN

In accordance with the present invention there is provided a sustained release aspirin preparation, which comprises a plurality of crystals which disperse in the gastrointestinal tract to avoid localized irritation, the coated crystals also providing a sustained release with the release of the aspirin over a period of at least about eight hours, thereby reducing the appli¬ cation of aspirin to a patient in need thereof. While read inistration of aspirin for headaches may not pose a major inconvenience, it is to be particularly noted that for an adult suffering from arthritis who may need an at least eight hour protection to avoid being wakened from the pain of such arthritis (or other chronic disease) during a normal period of overnight sleep, the provision of a sustained release form that provides an at least eight hour protection is highly desirable. Instead of waking in the early morning hours due to pain caused when the effect of normal aspirin taken before retiring has worn off, with the sustained release aspirin prepa¬ ration of the present invention it is possible for the pain relief to last until the normal waking time of the patient, permitting an unbroken sleeping pattern throughout the night. In addition to the use of the instant sustained release aspirin for those suffering from arthritis and other chronic illnesses, another important use of the coated crystals of the present invention is pediatric, to provide an ^*•overnight" dosage of aspirin for small children who often run high fevers and, without such an overnight dosage, would be awakened in the middle of the night. In its generic aspect, the present invention provides a sustained release aspirin dosage form to permit the continuous delivery of aspirin into the gastrointestinal tract for a period of at least eight hours which comprises a plurality of polymerically coated aspirin crystals which each comprise an aspirin seed, the majority of aspirin seeds having a mesh size of from about 30 to about 60 mesh, each of said aspirin sees being individually coated with a polymeric mixture which comprises from about 1.5 to about 15 parts by weight ethylcellulose and about one part by weight hydroxypropylcellulose. The dosage form may be, for example, a capsule, which in the case of an adult or older child may be taken whole and which dissolves in the stomach, there releasing the polymerically coated aspirin tablets. For smaller children or geriatric pa¬ tients who either are unable or unwilling to swallow a whole capsule, the drug may be sprinkled onto food or mixed with a beverage and so taken, the polymeric coat¬ ing masking the unpleasant taste of the aspirin. For this mode of administration the dosage form may be, for example, a capsule that is easily opened without diffi¬ culty, to avoid spilling of the contents. For example, a preferred embodiment for a capsule to be used merely to store the drug, and not necessarily to be swallowed, is disclosed in Keith, "Anti-Spilling Drug Capsule," United States patent application Serial No. 338,257, filed January 11, 1982, the entire specification of which is hereby incorporated by reference herein. In another embodiment of this aspect of the present inven¬ tion, a sealed pouch preferably constructed of a poly¬ ester film (Mylar) may be used to house the polymeri¬ cally coated aspirin crystals. Although the aspirin that is used as the "seed" for the present invention may be granulated or may be compounded with other conven¬ tional tableting ingredients, in accordance with a preferred aspect of the present invention it is contem¬ plated that pure aspirin crystals may be used. The aspirin, furthermore, should have a relatively uniform particle size distribution, which has been found to be important to achieving relative linearity of release over a prolonged period of time. Accordingly, the aspirin "seeds" should be selected for a particle size which ranges from about 30 to about 60 mesh. It is contemplated that while minor amounts of the aspirin seeds may fall outside this range, the number of such particles should be minimized, the predominant propor¬ tion of the total aspirin seeds being in the about 30 to about 60 mesh size range, particles outside that range being tolerated only to the extent that they do not destroy the relative linearity of release over the required period of at least about eight hours delivery of the aspirin in the gastrointestinal tract.

The polymeric coating requires a major component of ethylcellulose and a minor component of hydroxypropyl- cellulose, it being required that the weight ratio of ethylcellulose to hydroxypropylcellulose be at least about 2.5. Accordingly, in one aspect of the present invention it is contemplated that said weight ratio be from about 2.5:1 to about 15:1, with a preferred range being from about 3.5:1 to about 12:1, and still more preferably about 9:1. The combined weight of the poly¬ meric coating is from about 3 to about 10% of the total weight of the polymerically coated aspirin crystal, and in a preferred embodiment is about 5% of such total weight.

While the total dosage in a dosage unit may vary dependent upon the ultimate use, it is contemplated that a single dosage unit form for adult use for a period of at least about eight hours is about 800 g (325 mg = 5 grain, the usual adult aspirin tablet) , an adult taking one or two dosage units. In a typical dosage unit form there are present on the order of 1000 polymerically coated aspirin seeds.

The following examples serve to illustrate the invention:

EXAMPLE I

700 gm aspirin crystals, all having a size of be¬ tween 30 and 60 mesh, are placed in a six inch air sus¬ pension coating column (Wurster column of manufacture by Glatt, West German) and coated with a mixture of 368 ml polymer solution which contained 29.4 gm ethylcellulose ["Ethocel N-10" (Dow)] and 7.4 gm hydroxypropylcellulose ["Klucel LF" (Hercules) ] and 92 ml methanol. The coat¬ ing solution is sprayed at 2.5 bar pressure with the liquid feed rate of 60 ml/minute. The inlet air tem¬ perature is about 60°C. After completion of the feed of the coating, the quickly dried polymerically coated aspirin crystals are recovered from the bottom of the air suspension coating.

EXAMPLE II

The polymerically coated aspirin crystals of Exam¬ ple I are tested according to U.S. . XX dissolution procedure. Thus, the test comprises a one hour resi¬ dence in simulated gastric fluid, followed by residence in simulated intestinal fluid. The following release of aspirin was observed through this testing procedure, confirming the relatively linear release of the aspirin into this simulated gastrointestinal tract for a period of over ten hours: -5-

Aspirin release after Percentage released

1 hour 11.5 %

2 30.7

4 53.5

6 69.8

8 84.6

10 96.2

The relatively linear release shown over the ten hour period indicates the use of the polymerically coated aspirin seeds of the present invention for uses requir¬ ing a sustained release for a period of at least eight hours.

Claims

WHAT IS CLAIMED IS:

1. A sustained release aspirin dosage form to permit the continuous delivery of aspirin into the gastrointestinal tract for a period of at least eight hours which comprises a plurality of polymerically coated aspirin crystals which each comprise an aspirin seed, the majority of aspirin seeds having a mesh size of from about 30 to about 60 mesh, each of said aspirin seeds being individually coated with a polymeric mixture which comprises from- about 1.5 to about 15 parts by weight ethylcellulose and about one part by weight hydroxypropylcellulose.

2. A sustained release aspirin dosage form of claim 1, wherein said dosage form is a capsule.

3. A sustained release aspirin dosage form of claim 1, wherein said dosage form is a sealed pouch.

4. A sustained release aspirin dosage form of claim 1, wherein the weight ratio between the ethylcellulose and hydroxypropylcellulose is from about 3.5:1 to about 12:1.

5. A sustained release aspirin dosage form of claim 4, wherein said weight ratio is about 9:1.

6. A sustained release aspirin dosage form of claim 1, wherein the polymeric coating is sprayed onto an aspirin crystal in an air suspension column and the total weight of the coating is from about 3 to about 10% by weight of the total product.

7. A sustained release aspirin dosage form of claim 6, wherein said total weight is about 5% of the total product.

8. A method of providing a patient in need of prolonged systemic delivery of aspirin for a period of at least about eight hours to relieve pain or fever which comprises the oral administration to said patient of a dosage form of claim 1, 2, 3, 4, 5, 6 or 7, whereby a sustained disintegration and release of the aspirin in the gastrointestinal tract takes place over a period of at least about eight hours.