Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-05-29
2002-10-15
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S464000, C424S451000, C424S499000, C424S489000, C424S501000, C424S502000, C424S450000, C514S681000
Reexamination Certificate
active
06465011
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to novel formulations comprising lipid-regulating agents.
BACKGROUND OF THE INVENTION
2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoic acid, 1-methylethylester, also known as fenofibrate, is representative of a broad class of compounds having pharmaceutical utility as lipid regulating agents. More specifically, this compound is part of a lipid-regulating agent class of compounds commonly known as fibrates, and is disclosed in U.S. Pat. No. 4,058,552.
Fenofibrate has been prepared in several different formulations, c.f., U.S. Pat. Nos. 4,800,079 and 4,895,726. 4,895,726 discloses a co-micronized formulation of fenofibrate and a solid surfactant.
U.S. Pat. No. 4,961,890 discloses a process for preparing a controlled release formulation containing fenofibrate in an intermediate layer in the form of crystalline microparticles included within pores of an inert matrix. The formulation is prepared by a process involving the sequential steps of dampening said inert core with a solution based on said binder, then projecting said fenofibrate microparticles in a single layer onto said dampened core, and thereafter drying, before said solution based on said binder dissolves said fenofibrate microparticles, and repeating said three steps in sequence until said intermediate layer is formed.
European Patent Application No. EP0793958A2 discloses a process for producing a fenofibrate solid dosage form utilizing fenofibrate, a surface active agent and polyvinyl pyrrolidone in which the fenofibrate particles are mixed with a polyvinyl pyrrolidone solution. The thus obtained mixture is granulated with an aqueous solution of one or more surface active agents, and the granules thus produced are dried.
PCT Publication No. WO 82/01649 discloses a fenofibrate formulation having granules that are comprised of a neutral core that is a mixture of saccharose and starch. The neutral core is covered with a first layer of fenofibrate, admixed with an excipient and with a second microporous outer layer of an edible polymer.
U.S. Pat. No. 5,645,856 describes the use of a carrier for hydrophobic drugs, including fenofibrate, and pharmaceutical compositions based thereon. The carrier comprises a digestible oil and a pharmaceutically-acceptable surfactant component for dispersing the oil in vivo upon administration of the carrier, which comprises a hydrophilic surfactant, said surfactant component being such as not to substantially inhibit the in vivo lipolysis of the digestible oil.
Sheu, M. T., et al,
Int. J. Pharm.
103 (1994) 137-146, reported that a dispersion of fenofibrate in PVP still maintains the same crystalline form of the drug itself.
Palmieri, G. F., et al,
Pharma Sciences
6 (1996) 188-194, reported that a dispersion of crystalline fenofibrate could be prepared in PEG 4000. The authors concluded solid solutions in PEG are formed when the amount of fenofibrate is less than 15% and the dissolution rate is increased, particularly for the 90/10 carrier/drug ratio.
Gemfibrozil is another member of the fibrate class of lipid-regulating agents. U.S. Pat. No. 4,927,639 discloses a disintegratable formulation of gemfibrozil providing both immediate and sustained release, comprising a tablet compressed from a mixture of a first and second granulation, and a disintegration excipient operable to effect partial or complete disintegration in the stomach. The first granulation comprises finely divided particles of pure gemfibrozil granulated with at least one cellulose derivative, and the second granulation comprises finely divided particles of pure gemfibrozil granulated with a pharmaceutically-acceptable water soluble or insoluble polymer which are then uniformly coated with a pharmaceutically-acceptable (meth)acrylate copolymer prior to admixture with the first granulation. The first and second granulations are present in the final composition in a ratio of from about 10:1 to about 1:10.
U.S. Pat. 4,925,676 discloses a disintegratable gemfibrozil tablet providing both immediate and enteric release, which is compressed from a mixture of a first granulation of gemfibrozil with at least one acid-disintegratable binder, and a second granulation formed from the first granulation, but regranulated or coated with an alkali-disintegratable formulation of at least one substantially alkali-soluble and substantially acid-insoluble polymer.
Another class of lipid-regulating agents are commonly known as statins, of which pravastatin and atorvastatin are members. U.S. Pat. Nos. 5,030,447 and 5,180,589 describe stable pharmaceutical compositions, which when dispersed in water have a pH of at least 9, and include a medicament which is sensitive to a low pH environment, such as prevastatin, one or more fillers such as lactose and/or microcrystalline cellulose, one or more binders, such as microcrystalline cellulose (dry binder) or polyvinylpyrrolidone (wet binder), one or more disintegrating agents such as croscarmellose sodium, one or more lubricants such as magnesium stearate and one or more basifying agents such as magnesium oxide.
It is an object of the present invention to provide formulations of lipid-regulating agents having enhanced bioavailability when compared to commercially available formulations.
SUMMARY OF THE INVENTION
The present invention is directed to a solid formulation comprising the lipid-regulating agent dispersed in a hydrophilic, amorphous polymer in which said lipid-regulating agent is present as a metastable, amorphous phase. The size reduction obtained through the preparation of a dispersion is usually difficult to obtain. However, by using any technique that results in the dispersion of the lipid-regulating agent in an amorphous polymer, such as, for example, solvent evaporation or fusion, results in an increase in the dissolution rate and oral bioavailability of the said lipid-regulating agent.
The formulation may be administered directly, diluted into an appropriate vehicle for administration, encapsulated into hard gelatin shells or capsules, or compressed into tablets, for administration, or administered by other means obvious to those skilled in the art.
REFERENCES:
patent: 4058552 (1977-11-01), Mieville
patent: 4800079 (1989-01-01), Boyer
patent: 4895726 (1990-01-01), Curtet et al.
patent: 4927639 (1990-05-01), Ghebre-Sellassie et al.
patent: 4961890 (1990-10-01), Boyer
patent: 5030447 (1991-07-01), Joshi et al.
patent: 5180589 (1993-01-01), Joshi et al.
patent: 5645856 (1997-07-01), Lacy et al.
patent: 5798375 (1998-08-01), Tsujita et al.
patent: 5807834 (1998-09-01), Morehouse
patent: 6074670 (2000-06-01), Stamm et al.
patent: 0 462 066 (1991-12-01), None
patent: 0793958 (1997-02-01), None
patent: 8201649 (1982-05-01), None
patent: 96/36318 (1996-11-01), None
patent: 98/15264 (1998-04-01), None
patent: 98/31361 (1998-07-01), None
K. R. Morris, et al., Characterization of humidity-dependent changes in crystal properties of a new HMG-CoA reductase inhibitor in support of its dosage form development, International Journal of Pharmaceuticals, vol. 108, No. 3, (1994) 195-206.
M. Sheu, et al., Characterization and dissolution of fenofibrate solid dispersion systems, International Journal of Pharmaceutics, 103 (1994) 137-146.
G. Palmieri, et al, Characterization and dissolution studies of PEG 4000/fenofibrate solid dispersions, S.T.P. Pharma Sciences 6 (3) 186-194 1996.
Fort James J.
Krill Steven L.
Law Devalina
Schmitt Eric A.
Abbott Laboratories
Page Thurman K.
Pulliam Amy
Wood Phillips Katz Clark & Mortimer
LandOfFree
Formulations comprising lipid-regulating agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Formulations comprising lipid-regulating agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Formulations comprising lipid-regulating agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2929299