Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-08-11
2002-04-09
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S464000, C424S465000, C424S468000, C424S490000, C514S770000, C514S772300, C514S777000, C514S778000, C514S781000
Reexamination Certificate
active
06368625
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the fields of pharmacy and medicine and to orally disintegrable dosage forms for the delivery of sustained or extended release microcapsules and/or prompt release coated or non-coated drug particles.
BACKGROUND OF THE INVENTION
There are many formulations known for administering extended or sustained release forms of various medicines. A common method involves the administration of microencapsulated or otherwise coated drug substances. Coating can be errodable or disintegrable or it can be selectively porous, effectively controlling the release or diffusion of the drug contained within it. The administration of such particles is, not without complexity. Tableting may crush the particles interfering with their otherwise preplanned drug administration rate. Suspension or liquid vehicles may be desirable, but the potential for leakage of the drug is increased. Capsules containing granules or beads may be an alternative. However, each new coating stage adds additional complexity and can modify the overall release profile of the drug.
Indeed, this latter problem is common to tablets as well. While much care may be taken in ensuring that the microencapsulated drug will release at a certain rate, placing sufficient material into a hard tablet for ingestion can change the release profile. It will take some time for the body to sufficiently digest the tablet and allow it to decompose or disintegrate into its component parts thereby releasing the microcapsules or microparticles. This adds an additional variable to the release profile and complicates formulation significantly.
One method of addressing these complications is by the provision of in-mouth, rapidly disintegrable tablets. These tablets will disintegrate in the mouth and release the microcapsules or microparticles which can then be swallowed. In essence, the tablet is useful for conveying the microencapsulated materials to the body. However, it disintegrates sufficiently rapidly such that it will not become an impediment or a significant factor in the overall release profile. By the use of this technology, ideally the release rate and profile of the drug would be identical to that of a standard tablet which is ingested or to that of an equivalent amount of microparticles which are swallowed.
Nonetheless, there is considerable room for improvement. Sustained-release or extended-release microcapsules and microparticles tend to be relatively larger and are often relatively hard. If an in-mouth delivery system is used, these particles are then released into the mouth and produce a sandy or gritty feel. This feel is exacerbated by large quantities of microencapsulated materials and/or the inclusion of relatively larger, tactily more significant, particles. It is an aim of the invention to address this problem.
Other problems are encountered in the formulation of prompt release, orally disintegrable tablets, especially those containing taste masked drug substances. These problems include “local accumulation.” Upon disintegration in the mouth, local accumulations of powder may occur which are not immediately swallowed. Powder may adhere to various parts of the oral cavity such as the tongue, mucus membranes and between the teeth. These local accumulations of powder may have an unpleasant mouth fee. Moreover, if the dosage form contains unpleasant tasting drug particles which are taste masked by means of coating, adherence in the oral cavity allows a greater opportunity for dissolution of the coating and, hence, release of the drug into the oral cavity. The dissolved drug diffuses through the saliva to reach the taste buds, resulting in the patient experiencing an unpleasant taste.
SUMMARY OF THE INVENTION
The present invention solves these problems by, in one aspect, providing an orally disintegrable tablet suitable for use in the delivery of sustained or extended release formulations of coated granules, coated particles or microcapsules.
Applicants have found that a method of addressing the distasteful sensation which may accompany the use of extended or sustained release coated formulations is by providing a material which will decompose or disintegrate in the mouth so as to form a relatively viscous slurry with saliva. This viscous saliva slurry will help contain the particles as a loose but cohesive mass thereby preventing the particles from distributing throughout the mouth, i.e., under the tongue, between the gums and lips, etc. This therefore provides a greatly enhanced organoleptic sensation. This is accomplished by providing an in-mouth disintegrable formulation (orally disintegrating tablets, capsules, etc.) that includes an in-mouth viscosity enhancer which provides a pleasant mouth feel and helps to cause the individual particles to associate with each other and with saliva to thereby incorporate the extended release particles into a salivary mass of increased viscosity. This in turn allows the particles to stay together and glide smoothly and be easily swallowed. This in-mouth viscosity enhancing material can be, for example, an in situ formed gel or a material such as gums or various polymers. Mixtures are also contemplated.
The tablet preferably contains between about 10 and about 80% of an extended release coated material by weight of the tablet. For convenience, we will refer herein to these coated materials as “microcapsules.” However, it should be understood that this term contemplates the use of any extended, enteric or sustained-release vehicle, including microgranules, granules, microcapsules, particles, microparticles, adsorbates and the like known in the industry. Indeed, these particulate materials, referred to collectively herein as “microcapsules,” need not necessarily be coated at all; so long as they can achieve an extended release. These microcapsules generally have a particle size ranging from between about 50 to about 3,000 microns and include between about 5 and about 70% of a coating based on the weight of the microcapsules. The coating is an extended or enteric release coating.
The tablet also generally includes between about 5 and about 60% of a rapidly dissolvable sugar or sugar alcohol filler. The rapidly dissolvable sugar or sugar alcohol filler has a particle size selected to be complementary to the particle size of the microcapsules and generally ranges between about 300 and about 1,500 microns. The tablet also includes between about 0 and about 35% of a binder, including insoluble filler-binders, between about 1 and about 40% of a disintegrant; and between about 0 and about 50% of an effervescent couple. The sugar or sugar alcohol, binder disintegrant and if present, the effervescent couple are all provided in amounts based on the weight of the finished tablet.
By the use of the present invention one can develop in-mouth disintegrable tablets which can disintegrate in the mouth in under a minute, preferably under 30 seconds. The thus disintegrated tablet releases the sustained or extended release microcapsules into the mouth. The use of the viscosity enhancer helps to maintain the available saliva, excipients and microparticles as an integral mass. However, the resulting slurry remains both easy and pleasurable to swallow.
The present invention therefore solves the problems facing the prior art. Even with relatively large microcapsules, it is possible to obtain a dosage form which can disintegrate rapidly in the mouth and yet results in a pleasant organoleptic mouth feel. Relatively large microcapsules can be released into the mouth without a significant amount of chewing which could break the microcapsules and/or alter their release profile. The microcapsules are bound together, in a loose confederation, which reduces this tendency to dissipate throughout the mouth of the patient causing irritation, discomfort, and an adverse organoleptic sensation. Ideally, the pharmoco-kinetic performance of the drug administered through this dosage form will not be in any way altered by a comparison of the direct administration of equal amounts of non-table
Khankari Rajendra K.
Kositprapa Unchalee
Pather S. Indiran
Siebert John M.
Cima Labs Inc.
Lerner David Littenberg Krumholz & Mentlik LLP
Spear James M.
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