Tablets comprising a cellulose ether are known to the pharmaceutical drug delivery art. For example, tablets containing the cellulose ether hydroxypropylmethycellulose are known in U.S. Pat. Nos. 3,870,790; 4,140,755; 4,167,588; 4,226,849; 4,259,314; 4,357,469; 4,369,172; 4,389,393 and 4,540,566.
The tablets known to the prior art using the hydroxypropyl-methylcellulose ether often have certain disadvantages associated with their structure and with their use. For example, the mechanical integrity of some prior art tablets frequently is insufficient to provide both a sustained and a rate controlled release of a drug over a prolonged period of time in a moving fluid environment of use. The prior art tablets often exhibit insufficient mechanical integrity, that is the cohesive ability to stay together in a moving fluid environment such as the gastrointestinal tract, without prematurely breaking-up and without prematurely releasing all of its drug content. The above-mentioned desirable properties are not readily apparent in the prior art tablets, which appear to undergo substantial disintegration in a short time span, usually less than eight hours in a fluid environment of use.
Another disadvantage associated with the prior art tablets is that they exhibit an unwanted, variable, and difficult to reproduce a rate of release pattern. For example, prior art tablets comprising a small amount of a cellulose ether exhibit this behavior, such as by tablets consisting of less than five weight percent of a hydroxypropylmethylcellulose having a number average molecular weight greater than 50,000. The presence of the small amount of this high molecular weight polymeric ether in the tablet masks the release characteristic of other polymeric ethers in the tablets resulting in an erratic release pattern which is difficult to reproduce from batch to batch and from tablet to tablet.
Still other unacceptable disadvantages associated with the prior art tablets are that the tablets during their shelf-life can exhibit an unpredictable change in their release-rate characteristics; the prior art tablet when tested in an in vitro test that substantially reproduces the in vivo environment of the gastrointestinal tract often releases the drug at a greater rate of release in vivo than in vitro, which difference can be attributed to a premature disintegration of the prior art tablet; and the prior art tablet in a high fluid shear environment releases its drug too quickly, usually in less than six hours and these tablets therefore are not adapted to prolonged release.
Thus, in the light of the above presentation it will be appreciated by those versed in the dispensing art, that if a novel dosage form is made available to the medical and the pharmaceutical arts for dispensing a difficult to deliver drug free of the tribulation known to the prior art, such a dosage form would have a definite use and would also be a valuable contribution to the dispensing art. It will be further appreciated by those versed in the dispensing art that if a dosage form can be provided that (a) possesses a desirable rate of release and mechanical properties for dispensing a drug over a prolonged period of time, and which dosage form (b) can be manufactured at an economical cost, such a dosage form would have a positive and a practical value and it would also represent an advancement in the dispensing arts.