Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1998-09-03
2001-07-03
Dudash, Diana (Department: 1619)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S493000, C424S494000
Reexamination Certificate
active
06254891
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the extended release administration of medication. More particularly, the invention relates to an acetaminophen composition that has particular in vitro acetaminophen release characteristics and is adapted for use by human patients that have difficulty swallowing acetaminophen tablets, caplets or capsules.
BACKGROUND OF THE INVENTION
Coating medication to effect a controlled or extended release administration profile is well known in the art. Drug manufacturers have been using such methods to provide oral administration of medications that enter the body over a predetermined, extended period of time.
Controlled release administration provides many benefits to a patient. For example, controlled release administration can reduce the number of times that a patient is required to self-administer medication, thus reduce the possibility that the patient will forget to take his or her medication during the day Analgesics and antipyretics, such as acetaminophen are often self-administered over the course of a day to help alleviate pain or fever from which a person is suffering. Often, such symptoms can last for long periods of time. However, the symptoms need not affect the person's typical daily routine. Thus, the person may not remember to take his or her medication because of other daily activities.
As a result, it has become advantageous to provide an extended or controlled release analgesic drug for self-administration. Such controlled release administration can substantially reduce the number of times that a patient takes medication during the day. The controlled release properties also facilitate night time administration in that a controlled release coating can be provided to sufficiently extend over the period during which the person is asleep.
In preparing and applying a controlled or extended release coating it is known to prepare the medication in a quantity of small pellets, non-pareils or prills, which are small, generally spherically shaped form of the medication. The prills are coated with, for example, an aqueous, ethyl-cellulose based film coating product, which dissolves when subjected to humidity or liquid aqueous media. The prills can be contained within a gelatin capsule or blister. The capsule, like the ethyl-cellulose coating, dissolves when subjected to humid conditions or liquid aqueous media. The blister is typically not administered to a patient, but rather is opened or separated and the contents emptied therefrom for use.
One method of applying the coating to the prills utilizes a technique referred to in the art as panning. This technique was originally developed for sugar-coating and is discussed by S. C. Porter in “Coating of Pharmaceutical Dosage Forms”,
Remington's Pharmaceutical Sciences,
18th ed., A. R. Gennaro ed., Chapter 90, Mack Publishing Co., Easton Pa. (1990) pages 1666-1675.
U.S. Pat. No. 4,820,522 teaches the preparation of a sustained release acetaminophen preparation that includes hydroxyethyl cellulose as an excipient and povidone (polyvinyl pyrrolidone) as a granulating agent to form a shaped and compressed medicament. The resulting compressed medicament is provided in the form of a compressed tablet or as a layer of a multilayered tablet. In this composition, the povidone, hydroxyethyl cellulose and other ingredients bind the acetaminophen in a sustained release solid matrix. A composition of this patent is stated to further require the inclusion of a “wicking agent” such as microcrystalline cellulose to wick fluids into the matrix and also an “erosion promoter” such as pregelatinized starch. Although a composition of this patent provides sustained release of acetaminophen to normal adults, such a composition is tableted and as such, cannot provide the medication to a patient who has difficulty swallowing a tablet.
Accordingly, there continues to be a need for an extended release acetaminophen composition that can be used to treat children and adults who have difficulty swallowing tablets or capsules, and that exhibits a predictable profile for the extended release of the acetaminophen over a period of time.
SUMMARY OF THE INVENTION
The present invention contemplates an extended release composition of acetaminophen in the form of generally spherical particles. The particles can be administered in a gelatin capsule or blister, and the contents administered in the gelatin capsule to adults that can swallow such capsules or the contents of the capsule or blister can be emptied therefrom and dispersed in an edible medium such as applesauce that can be swallowed by patients such as children that cannot swallow or have difficulty swallowing tablets, caplets or capsules.
A contemplated extended release acetaminophen composition comprises a plurality of discrete particles containing acetaminophen coated on sugar/starch seeds. All of these particles are free of a wicking agent and an erosion promoter as required and utilized in U.S. Pat. No. 4,820,522. The particles are present as a blend of both an immediate release and a controlled release form. The composition, when present in a gelatin blister and assayed in a USP Apparatus I rotating basket at 50 rpm in 900 milliliters (mL) of phosphate buffer at pH 5.8 and 37° C., exhibits about 40 percent acetaminophen dissolution (released) at one-half hour, about 55 percent acetaminophen dissolution at one hour, and substantially complete dissolution of acetaminophen at six hours.
Advantageously, a contemplated extended release acetaminophen composition provides an extended or sustained release profile in a particle- or prill-containing gelatin capsule or blister. A contemplated composition can thus be dispersed or sprinkled on, for example, food such as applesauce, so that it can be administered to a patient that, otherwise has difficulty taking, or could not take a “solid” tablet or caplet. Thus, the present extended release composition now provides long term analgesic administration for patients who otherwise could not obtain such relief.
It is to be understood that reference herein to gelatin capsule, capsule or blister is made only for the purpose of describing or providing various alternate packaging or “containing” vehicles for the composition of the present invention, and is not intended to limit the scope of the present invention. All such packaging or “containing” vehicles are thus within the scope of the present invention.
In a preferred composition, the controlled release particles comprise a sugar/starch seed particle coated with a plurality of layers of acetaminophen and magnesium stearate that are bound with povidone. Most preferably, the acetaminophen-containing layers are coated with a plurality of layers of a mixture of povidone and magnesium stearate. In a contemplated composition, the weight ratio of acetaminophen to magnesium stearate in the controlled release particles is about 5:1 to about 10:1, and acetaminophen comprises about 70 to about 80 weight percent of the controlled release particles.
Preferably, the immediate release particles also comprise sugar/starch seed particles, which seeds are coated with a plurality of layers of a mixture of acetaminophen, starch and cross-linked carboxymethyl cellulose bound with povidone. A preferred cross-linked carboxymethyl cellulose is croscarmellose NF. In a preferred composition, the immediate release particles contain acetaminophen, starch and cross-linked carboxymethyl cellulose in a weight ratio of about 13-16:1:1.5-2, respectively, and acetaminophen constitutes about 60-70 weight percent of the particles.
A preferred blend of the composition includes immediate release particles and controlled release particles in a weight ratio of about 1:1 to about 1:1.5, respectively.
The blend can also contain coated sugar/starch seeds that are free of acetaminophen. In one such blend, the immediate release particles, the controlled release particles and the coated sugar/starch seeds are present in a weight ratio of about 1:1-1.5:0.1-0.25.
A process for treating a human patient that h
Anaebonam Aloysius O.
Clemente Emmett
Mendes Robert W.
Ascent Pediatrics Inc.
Berman Alysia
Dudash Diana
Welsh & Katz Ltd.
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