Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-12-16
2001-04-24
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S435000, C424S441000, C424S465000, C424S469000, C424S484000
Reexamination Certificate
active
06221392
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the pharmaceutical industry, the medical industry, and, in particular, to the creation of dosage forms.
BACKGROUND OF THE INVENTION
It is known to produce an in-mouth disintegrable dosage form for the delivery of drugs. In fact, patents relating generally to this area date back to the last century. Such tablets have significant advantages over other dosage forms; particularly for those who cannot, or will not, swallow a tablet or capsule. Solid dosage forms are far more convenient than liquids. However, the design of orally disintegrable dosage forms carries with it its own set of unique problems.
Chewable tablets such as, for example, those disclosed in U.S. Pat. No. 5,225,197 to Bolt, can be provided. However, such dosage forms often provide inadequate taste-masking of bad tasting medicaments. Chewable formulations are also often incompatible with, for example, delicate microparticles or time-released microparticles. The compressive force used in forming tablets and/or during chewing will often rupture such structures either exposing the patient to the objectionable taste of the material contained therein, or interfering with the structural integrity of the encapsulant and thereby altering its drug delivery profile.
Non-chewable dosage forms have also been tried. For example, Cima Labs has produced oral dosage forms including microparticles and effervescents which rapidly disintegrate in the mouth and provide adequate taste-masking. See Wehling et al., U.S. Pat. No. 5,178,878. Zydis, on the other hand, produces a rapidly dissolvable, freeze-dried, sugar matrix to produce a rapidly dissolving tablet. While these dosage forms are effective, they provide significant problems in terms of production, storage, transport and during consumer usage. They are also significantly more costly to produce.
According to U.S. Pharmacopoeia No. 23, 1995, Chap. 1216 entitled “Tablet Friability,” the text of which is hereby incorporated by reference, effervescent tablets and chewable tablets often have different specifications as far as friability, when compared to normal tablets. These tablets normally require special packaging. That, however, is a great understatement.
The Zydis tablets, for example, are so fragile that the matrix material must be formed by freeze-drying in an individual tablet-sized container. While the use of an effervescent couple in combination with microparticles as disclosed in Wheling et al. does overcome the need for such extreme measures, the need to minimize in-mouth disintegration times still require the use of nontraditional packaging and processing methodology. For example, normal conveyors such as vibratory conveyors or bulk hoppers common in the pharmaceutical industry could not be used, as these high-speed, high-volume devices tend to cause damage to the resulting tablets. Similarly, the resulting tablets cannot be stored on a hopper after tableting but before packaging. This can seriously interfere with the processing efficiencies of high-volume presses.
Moreover, the resulting tablets have to be packaged in individual, blister-type packages that are robust enough to avoid tablet breakage. They could not be packaged in a conventional, multi-tablet bottle, individual foil pouches or traditional blister packaging.
SUMMARY OF THE INVENTION
The present invention relates to a hard, compressed, rapidly dissolvable dosage form adapted for direct oral dosing. The dosage form includes an active ingredient and a matrix. The matrix is composed of at least a nondirect compression filler and a lubricant. The dosage form is adapted to rapidly dissolve in the mouth of a patient and thereby liberate the active ingredient. Preferably, the dosage form has a friability of about 2% or less when tested according to the U.S.P. The dosage form also preferably has a hardness of 15-50 Newtons (“N”).
It is desirable that the dosage form dissolve in about 90 seconds or less in the patient's mouth. It is also often desirable that the dosage form include at least one particle. The particle would the active ingredient and a protective material. These particles can include rapid release particles and or sustained release particles.
In a particularly preferred formulation in accordance with the present invention there is provided a hard, compressed, rapidly dissolving tablet adapted for direct oral dosing. The tablet includes particles made of an active ingredient and a protective material. These particles are provided in an amount of between about 0.01 and about 75% by weight based on the weight of the tablet. The tablet also includes a matrix made from a nondirect compression filler, a wicking agent, and a hydrophobic lubricant. The tablet matrix comprises at least about 60% rapidly water-soluble ingredients based on the total weight of the matrix material. The tablet has a hardness of between about 15 and about 50 Newtons, a friability of less than 2% when measured by U.S.P. and is adapted to dissolve spontaneously in the mouth of a patient in less than about 60 seconds and thereby liberate said particles and be capable of being stored in bulk.
The dosage forms described above are able to dissolve rapidly in the mouth of the patient, with a minimum of grit or other organoleptically unpleasant species. Moreover, because the dosage forms are hard and have low friability they can be handled and packaged like other, nonrapidly dissolving dosage forms.
Therefore, in another aspect of the present invention, there is provided a method of making a packaged, orally dissolvable dosage form. The method includes the steps of:
(a) forming a mixture including an active ingredient and a matrix including a nondirect compression filler and a lubricant;
(b) compressing the mixture to form a plurality of hard, compressed, rapidly disintegrable dosage forms including the active ingredient distributed in the orally dissolvable matrix; and
(c) storing the dosage forms in bulk prior to packaging. In a preferred embodiment, the dosage forms are then packaged in a lumen of a package such that there is at least one per package. In a preferred particularly preferred embodiment, the dosage forms are then packaged in a lumen of a package such that there more than one per package. Direct compression is the preferred method of forming the dosage forms.
There is also provided hereby an openable and recloseable package containing a plurality of hard, compressed, rapidly dissolving tablets adapted for direct oral dosing as described above.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENT
The present invention is directed to a hard, compressed, rapidly dissolvable dosage form adapted for direct oral dosing. The dosage form includes an active ingredient often in the form of a protected particle, and a matrix. The matrix includes a nondirect compression filler and a lubricant, although, it may include other ingredients as well. The dosage form is adapted to rapidly dissolve in the mouth of a patient. Yet, it has a friability of about 2% or less when tested according to the U.S.P. Generally, the dosage form will also have a hardness of at least about 15-20 Newtons. Not only does the dosage form dissolve quickly, it does so in a way that provides a positive organoleptic sensation to the patient. In particular, the dosage form dissolves with a minimum of unpleasant grit which is tactilely very inconsistent with organoleptic sensation of the dosage form.
“Dosage form,” in accordance with the present invention, includes tablets and “slugged cores” used in capsules or caplets (a hybrid tablet/capsule). “Dissolvable,” should be understood as describing the action of the dosage form as it is held in the mouth. In this case, the dosage form gets continuously smaller in a process which is conceptually analogous to melting. While the dosage form may also disintegrate into smaller pieces to some extent, particularly where a relatively greater amount of a wicking agent or effervescent disintegrant is used, or where the dosage form is chewed, that is not its principal mechanism. T
Chastain Sara J.
Hontz John
Katzner Leo
Khankari Rajendra K.
Cima Labs Inc.
Lerner David Littenberg Krumholz & Mentlik LLP
Spear James M.
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