Taste masked pharmaceutical compositions

Details Taste masked pharmaceutical compositions Taste masked pharmaceutical compositions

2002-02-26

2004-07-27

Spear, James M. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Particulate form

C514S974000

Reexamination Certificate

active

06767557

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel taste masked pharmaceutical compositions. More particularly, this invention relates to taste masked pharmaceutical compositions comprising microcapsules for reconstitution with a liquid vehicle for oral administration, which effectively mask the taste of pharmaceuticals or nutritional supplements that have a bitter or otherwise undesirable taste characteristic.
BACKGROUND OF THE INVENTION
Pharmaceutically active agents can be administered to the patient in many forms with oral administration being the most popular. Active agents can be given to the patient orally as liquid solutions, emulsions, suspensions or in solid form such as capsules or tablets. Infants, children, older persons and many other persons are unable to swallow whole tablets and capsules. Therefore, in cases where the dosage to be administered cannot be made into a very small tablet or capsule, it is desirable to provide the medicine in liquid or chewable form, direct administration as a powder or granules in suspension would also be advantageous.
Many active ingredients, such as antibiotics, possess a strong, unpleasant taste. In particular, unpleasant-tasting active ingredients include gyrase inhibitors; particularly, those of the naphthyridone-carboxylic acid and quinolone-carboxylic acid types; more particularly, those selected from levofloxacin, ciprofloxacin, norfloxacin, ofloxacin or enoxacin.
When an active agent is formulated as a tablet or capsule intended to be swallowed whole, the taste of the active ingredient is usually not an issue since the capsule keeps the active ingredient from contacting the mouth and the tablet can be coated to prevent contact of the active with the mouth for the short time the tablet is present in the mouth. In contrast, masking of the unpleasant taste characteristics of the active agent is an extremely important factor in the formulation of liquid and chewable pharmaceuticals. The palatability of the liquid or chewable dosage form is a critical factor in ensuring patient compliance.
In some cases, the unpleasant taste of the active agent in a liquid or chewable formulation can be overpowered by adding flavoring ingredients and sweeteners to improve taste and palatability. However, where the active agent possesses a particularly strong or bitter taste, such as is the case with many antibiotics, the mere addition of such flavoring ingredients and sweeteners is insufficient to improve taste and palatability. Accordingly, various taste masked coating compositions have been employed in the formulation of liquid suspension and chewable tablet dosage forms.
Besides a complete concealment of the taste, a rapid and complete release is critical for the beneficial effects of an active ingredient to be made available to a patient. The composition, though, must also preserve the stability of the active ingredient in a humid environment prior to use. For a coated granule composition to ensure bioavailability that is equivalent to a tablet formulation, the coating must be formulated to release the active ingredient in an appropriate environment.
For example, it is known for numerous active ingredients that there is an absorption window in the upper small intestine and that absorption in the lower intestine is greatly reduced (S. Harder, U. Fuhr, D. Beermann, A. H. Staib,
Br. J. Clin. Pharmac.,
1990, 30, 35). In elderly people, there are also frequently occurring deviations of the gastric pH in the direction of a hypoacidic medium. In an attempt to ensure bioavailability, therefore, certain water-insoluble coated formulations (using a “reverse enteric coating”) have been designed to dissolve in a weakly acidic medium such as one having a pH 4.5, for example, the acidic environment of the stomach. We have discovered that the use of a reverse enteric coating formulation, however, does not result in reproducible bioavailability to all patients due to the physical variability among patients in passage of a reverse enteric coating formulation through the gastrointestinal tract.
U.S. Pat. No. 5,599,556 discloses liquid formulations where the active ingredient is coated with a single outer polymeric coating derived from prolamine cereal grain proteins and a plasticizing agent. The coatings are designed to rapidly degrade once the composition leaves the mouth.
U.S. Pat. No. 5,489,436 discloses chewable tablets made from a coated medicament where the coating is a “reverse enteric coating” designed to be soluble at the acidic pH of the stomach but relatively insoluble in the mouth. The coatings comprise a polymer blend of dimethylaminoethyl methacrylate and neutral methacrylic acid ester and a cellulose ester.
U.S. Pat. No. 6,136,347 discloses taste-masked microcapsules for use in liquid suspension formulations, particularly in oil-based juices or a suitable liquid such as water. The microcapsule comprises an active ingredient granule coated with a single outer polymeric coating derived from film-forming agents such as neutral methyl and ester compounds of polymethacrylic acid. The coatings are designed to be water-insoluble and rapidly degrade once the composition reaches the acidic environment of the stomach.
There is thus a need for a water-insoluble taste masked composition which is stable, bioavailable and retains its coating integrity and, thereby, its taste masking properties in an aqueous, pH-neutral or pH-acidic environment over an extended period, yet which exhibits immediate bioavailability after passage into the intestine.
An object of the present invention is to provide taste masked pharmaceutical compositions. An object of the present invention is to provide taste masked pharmaceutical compositions comprising microcapsules, for reconstitution with a liquid vehicle for oral administration.
SUMMARY OF THE INVENTION
The present invention provides taste masked pharmaceutical compositions comprising a microcapsule, wherein the microcapsule comprises a pharmaceutically active agent core coated with a taste masking effective amount of a water-insoluble enteric coating, wherein the coating comprises a weakly acidic methacrylic acid-ethyl acrylate copolymer.
An embodiment of the invention is a taste masked pharmaceutical composition wherein the pharmaceutically active agent is an antibiotic drug.
Another embodiment of the invention is a taste masked pharmaceutical composition wherein the antibiotic drug is selected from levofloxacin.
An embodiment of the invention also includes a method for reconstituting a taste masked pharmaceutical composition according to the invention in a liquid vehicle such as an oily juice for oral administration.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides taste masked pharmaceutical compositions comprising microcapsules, wherein the microcapsules comprise a pharmaceutically active agent coated with a taste masking effective amount of a water-insoluble enteric coating, wherein the coating comprises a weakly acidic methacrylic acid-ethyl acrylate copolymer.
The invention relates in particular to a taste masked pharmaceutical composition comprising a pharmaceutically active agent having an unpleasant taste that is coated with an enteric coating. Enteric coatings are those that are insoluble at the acidic pH levels of the stomach and are soluble in the basic pH of the intestine. The coatings provide a protective layer which masks the unpleasant taste characteristics of the active ingredient while passing through the mouth and which remains stable in the acid environment of the stomach because of its low solubility therein, but is readily soluble in the intestine and, thereby, provides immediate release of the active agent in the intestine. The enteric coatings encapsulate the active ingredient, effectively and stably masking the taste of the active agent while providing reproducible bioavailability to a varied patient population.
The taste masked pharmaceutical composition of the present invention utilizes an enteric coating which is weakly acidic, soluble in the basic pH of the i

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