EP1107740A1

EP1107740A1 - Timed release tablet comprising naproxen and pseudoephedrine

Info

Publication number: EP1107740A1
Application number: EP98941051A
Authority: EP
Inventors: Chris E. Platt
Original assignee: Individual
Current assignee: Individual
Priority date: 1998-08-25
Filing date: 1998-08-25
Publication date: 2001-06-20
Also published as: EP1107740A4; MXPA01001969A; AU758880B2; JP2002523358A; AU8919898A; CA2341485A1

Abstract

Pharmaceutical compositions and methods of using same comprising non-steroidal anti-inflammatory analgesic naproxen and the decongestant pseudoephedrine in a time release tablet form in the therapy or cure of sinusitis, or sinus headaches, generally exemplified by discomfort, pain, pressure, and dizziness.

Description

TIMED RELEASE TABLET COMPRISING NAPROXEN AND PSEUDOEPHEDRINE

BACKGROUND OF THE INVENTION

The present invention relates generally to novel pharmaceutical

compositions of matter comprising the non-steroidal anti-inflammatory

analgesic naproxen in combination with the decongestant

pseudoephedrine and appropriate non-toxic carriers and to methods of using said compositions in the therapy or cure of sinusitis, or sinus

headaches, generally exemplified by discomfort, pain, pressure, and dizziness.

Non-narcotic analgesics, commonly known as non-steroidal anti-

inflammatory drugs, such as naproxen, are widely administered orally in the treatment of mild to severe pain. These drugs have been disclosed

as useful in treating cough/cold symptoms in combination with certain

antihistamines and decongestants. See, for example U.S. Pat. No.

4,552,899 to Sunshine.

Naproxen as non-steroidal anti-inflammatory pain reliever has greater advantage than other pain relievers acetaminophen, aspirin, and

ibuprofen. Naproxen has a significantly greater duration or half-life that leads to twice a day dosage. It is generally accepted that decreased dosing leads to patient convenience and better compliance.

Originally combinations of anti-inflammatories and anti-histamines or

decongestants were combined with no consideration to the vastly different

drug duration or half-lives. These drugs with different half-lives were not

combined in a synergistic manner which led the body effectively using

them at equal rates. This would lead to ineffective combinations of anti-

inflammatories and decongestants and the return of partial symptoms.

SUMMARY OF THE INVENTION

It is a primary object of the present invention to provide a novel timed-

release pharmaceutical composition of matter comprising an analgesically effective amount of naproxen and an effective amount of decongestant

pseudoephedrine with pharmaceutically acceptable excipients.

It is a further object of the present invention that administration of our specific ratio of composition optimizes the most effective drug level of

both drugs in the body over time for relief for nasal sinus congestion that causes headache pain, pressure, dizziness, and general malaise.

DETAILED DESCRIPTION OF THE INVENTION More specifically, the applicant herein has found that a timed-released combination product suitable for oral administration comprising naproxen and pseudoephedrine combined with or without an appropriate base salt. Through studying extensively the applicant has found that the preferred dosage form that provides for immediate release of naproxen and pseudoephedrine, and specific timed release of pseudoephedrine.

The release of naproxen and pseudoephedrine takes place together up to 12 hours, preferably 10 hours. One or two tablets are administered orally, preferably two. Concentration ranges for the active ingredients are naproxen, 50-500 mg per tablet; pseudoephedrine 30- 240 mg per tablet. The concentration ranges represent 7- 30% of coated tablet weight of pseudoephedrine and 15- 60% of naproxen.

The preferred dosage form is a coated tablet, wherein naproxen and pseudoephedrine are on the outer coating thus released immediately while pseudoephedrine in the core is released over time, preferably over the duration of the half-life of the naproxen, approximately 10 hours. The outer-coating dissolving rapidly to release both naproxen and pseudoephedrine and the inner core dissolves slowly to time release pseudoephedrine through hydration and diffusion of the drug from the core polymer.

The dosage range for naproxen is from 50-800 mg per day depending upon pain management requirements. The range of pseudoephedrine is between 30-240 mg per day depending blood pressure values and overall health of the patient. Both drugs will vary depending upon the age and weight of the patient, the seventy of the symptoms and the incidence of side effects for humans.

The core consists of common hydrophilic swellable polymers such as 25 hydroxypropylmethylcellulose (HPMC) or hydroxypropylcellulose either by themselves or in combination with each other. The hydrated polymers act as a binder that swells when hydrated by gastric media and delays absorption. The combination of polymers will represent about 15% of tablet core weight. The tablet outer coating comprises HPMC and a plasticizer such as polyethylene 30 glycohol (PEG) both which dissolve immediately in gastric fluids. Suitable coloring and flavoring agents may be included.

The tablet core also comprises excipients such as polymers, fillers, binders, lubricants, and antiadherents, all necessary for standard tablet manufacture. Binders are present at a concentration of 5% and typically are starch, gelatin, natural or artificial gums. Fillers are present at a concentration of about 10 to 20% of tablet core weight and may include starches or cellulose. Antiadherents used to prevent tablets from sticking to the tablet press typically include silicas and talc, are present from 0 to 6% of the tablet core weight. Typical lubricants are magnesium stearate, boric acid, or sodium benzoate at a concentration of about 2.5% to 5% of the tablet core weight. Additional binders used in the granulation of the drug polymer mixture include povidine and corn starch. Such binders are present at a concentration of about .5% to 3% of the tablet core weight. The means of preparing compositions of the present invention, e.g. tablet mixing, compaction, and coating are all well known to those skilled in the art.

EXAMPLE 1

Mg/tablet

A. Core Tablet

Pseudoephedrine Sulfate 30

Microcrystalline Cellulose 140

Povidone 15

HPMC/PEG 40

Magnesium Stearate 10

B. Outer Coatinα

Naproxen 100

Pseudoephedrine Sulfate 30

HPMC/PEG 10 Method of Manufacture

A. Outer Coating

1. Dissolve HPMC/PEG in an alcohol mixture.

2. Disperse Naproxen and Pseudoephedrine in the HPMCIPEG solution.

3. Coat inner tablets below with the solution using standard procedures.

B. Inner Core

1. Mix pseudoephedrine sulfate, microcrystalline cellulose and HPMC.

2. Dissolve povidone in an alcoholic mixture and use it to crystallate the powder mix.

3. Dry pseudoephedrine sulfate crystalate mix.

4. Compress into tablets.

While the invention is described and illustrated with reference to

certain preferred embodiments thereof, those skilled in the art will

appreciate that various changes or modifications can be made therein

without departing from the spirit of the invention For example, effective

dosages of the active ingredients other than the preferred ranges set forth

hereinabove may be used. It is intended that the invention be limited only by the scope of the claims that follow.

Claims

I claim:

1. A pharmaceutical composition consisting essentially of naproxen, pseudoephedrine, and inert ingredients to treat sinusitis in mammals.

2. A pharmaceutical composition in the form of a sustained release coated tablet, wherein the tablet has an outer coating consisting essentially of a combination of anti-inflammatory naproxen and a decongestant pseudoephedrine, with an inner core of pseudoephedrine in a time release form.

3. The pharmaceutical composition of claim 2 wherein the naproxen and pseudoephedrine consist essentially of pseudoephedrine at between approximately 7% and 30% of the coated tablet weight and naproxen at approximately 15% to 60% of the coated tablet weight.

4. The pharmaceutical composition of claim 2, further including a hydoxypropylmethylcellulose and hydroxyprophycellulose.

5. The pharmaceutical composition of claim 2 wherein the inner core further includes about 10 to 20% filler, zero to 6% antiadherents, 0.25% to 3% binder, of the total tablet core weight.

6. A pharmaceutical composition prepared by the process of : preparing an inner tablet core by mixing pseudoephedrine sulfate, microcrystalline cellulose and hydroxypropylmethylcellulose into a powder mix; drying the crystallate powder mix; compressing the dried crystallate powder mix into tablets; preparing an outer coating solution for the tablets by dissolving hydroxypropylmethylcellulose and polyethylene 30 glycohol in an alcohol mixture; and coating the inner dried crystallate tablets with the outer coating solution.