Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1997-06-10
2002-02-19
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S464000, C424S470000, C424S493000, C424S494000, C424S468000, C424S469000, C514S960000
Reexamination Certificate
active
06348216
ABSTRACT:
FIELD OF THE INVENTION
This invention is related to the field of pharmaceutical compositions and methods of preparing pharmaceutical compositions. Specifically, this invention is related to solid dosage compositions of ibuprofen in combination with a narcotic analgesic.
BACKGROUND OF THE INVENTION
Solid dosage forms of ibuprofen, a non-steroidal anti-inflammatory agent, are known. Although tablet compositions of ibuprofen are known and commercially available, problems of poor tablet compression, stability and disintegration persist and are well documented. For example, it is known that ibuprofen tablets made from wet granulation methods “age” over time which tends to have a negative impact on dissolution. (See U.S. Pat. No. 4,609,675 to Franz). Franz theorizes that the tablets “age” over time because of sintering which is described as a type of cementing of the ibuprofen particles to one another. Franz states that one way to minimize sintering is to increase the amount of excipients or diluents used in the compositions in order to isolate the ibuprofen particles. This causes problems in formulating high dose ibuprofen tablets because the tablets are too large when they are made by a wet granulation process. In an effort to overcome this problem, Franz prepared a dry granulation of high dose ibuprofen in combination with croscarmellose, noting that it was unexpected to formulate a successful composition in view of his experience that other disintegrants such as corn starch and crospovidone did not work. Franz also describes that croscarmellose improved dissolution characteristics of the tablets when they contained 1.34% to 7.01% croscarmellose but decreased dissolution characteristics when the tablets contained croscarmellose in excess of 7.01%.
U.S. Pat. No. 4,911,921 to Denton et al. notes that they were able to overcome the problem of using a large amount of excipients in wet granulation methods used to make ibuprofen tablets. Denton et al. notes that Franz was able to overcome these problems by using a dry mixing method using amounts of croscarmellose up to 15% and preferably about 7 to 8%. Denton describes the use of agglomerates of ibuprofen and binder held together by binder and polyvinylpyrrolidone. Denton et al. describes the use of a dry composition comprised of lactose.
Solid dosage forms of non-steroidal anti-inflammatory agents in combination with narcotic analgesics are known and have been described as providing a synergistic therapeutic for the relief of pain. For example, U.S. Pat. No. 4,690,927 to Voss et al. describes the preparation of diclofenac sodium and codeine phosphate tablets by mixing the diclofenac sodium and codeine with dicalcium phosphate, corn starch and colloidal silica. In Voss et al. the mixture is spray granulated with a solution of hydroxypropyl cellulose in deioinised water. The dried granulation is mixed with carboxymethyl starch, colloidal silica and magnesium stearate. The resulting blend is compressed into tablets and film coated. U.S. Pat. No. 4,587,252 to Arnold describes the treatment of pain using a combination of ibuprofen and hydrocodone. Arnold describes tablets containing flavoring agents, lubricants, solubilisers, suspending agents, binders, and disintegrants. Although Arnold lists many different ingredients that can be used in the tablets, the examples are directed to tablets that contain, along with other compounds, hydrocodone bitartrate, ibuprofen, microcrystalline cellulose, and magnesium stearate. The method of making the tablets is directed to a dry granulation process.
European Patent Application No. 68838A (Upjohn) also describes a combination product of a narcotic analgesic and ibuprofen. The tablets are generally described as containing agents such as diluents, binders, gelating solutions and methylcellulose. Specifically described tablets are directed to tablets containing lactose, corn starch, magnesium stearate and light liquid petrolatum.
Although solid dosage forms of non-steroidal anti-inflammatory agents in combination with narcotic analgesics are known, workers have discussed problems with formulating tablets containing both an analgesic narcotic and a non-steroidal anti-inflammatory drug. U.S. Pat. No. 4,839,176 to Pankhania et al describes a wet granulation method for making various strength ibuprofen and codeine phosphate tablets. The ibuprofen is mixed with microcrystalline cellulose, calcium carboxymethylcellulose and fumed silica. This combination of material is granulated using a solution of polyvinylpyrrolidone in isopropyl alcohol. The granules are sized, dried and blended with excipients such as calcium carboxymethylcellulose, fumed silica, stearic acid, and sodium metabilsulphite. Pankhania et al. states that the formulations are unexpectedly stable over time in view of the general knowledge that admixtures of ibuprofen and codeine are unsatisfactory for commercial use.
U.S. Pat. No. 4,844,907 to Elger describes multiphase tablets prepared by compressing narcotic analgesic granules with non-steroidal anti-inflammatory granules. Both granules are described as being prepared in the absence of magnesium stearate. Elger states that tablets made with a narcotic analgesic, a non-steroidal anti-inflammatory carboxylic acid and magnesium stearate, as described in European Patent Application Number 68838A, exhibit serious incompatibility, poor crushing strength and long disintegration times. Elger also presents comparative examples of “single phase” tablets with ibuprofen, codeine, microcrystalline cellulose and croscarmellose sodium and states that these tablets had poor disintegration times, poor crushing strengths or sticking problems.
The above discussion indicates that compositions made from both wet and dry granulation processes have not been completely effective in providing a composition with both ibuprofen and a narcotic analgesic wherein the composition has acceptable disintegration, dissolution and compression characteristics. The inventors have also found that direct compression methods produce compositions with poor content uniformity. The inventors have further found that direct compression methods produce tablets that have poor compressibility.
Thus, it is an object of the present invention to provide a composition containing ibuprofen and a narcotic analgesic having superior disintegration, dissolution and compression characteristics.
REFERENCES:
patent: 4569937 (1986-02-01), Baker et al.
patent: 4571400 (1986-02-01), Arnold
patent: 4587252 (1986-05-01), Arnold
patent: 4609675 (1986-09-01), Franz
patent: 4690927 (1987-09-01), Voss et al.
patent: 4839176 (1989-06-01), Pamkhania et al.
patent: 4844907 (1989-07-01), Elger et al.
patent: 4859704 (1989-08-01), Haas
patent: 4882167 (1989-11-01), Jang
patent: 4911921 (1990-03-01), Denton et al.
patent: 5164398 (1992-11-01), Sims et al.
patent: 5256699 (1993-10-01), Murphy et al.
patent: 0 068 838 (1983-05-01), None
Lachman, Leon “The Theory and Practice of Industrial Pharmacy” 1929, pp. 325-336, Great Britain.
PCT/US 97/09819 International Search Report dated Sep. 29, 1997.
Kushla Gregory P.
Lai Jin-Wang
Polli Gerald P.
DeConti, Esq Giulio A.
Knoll Pharmaceutical Company
Lahive & Cockfield LLP
Lauro, Esq. Peter C.
Page Thurman K.
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