Formulations comprising lipid-regulating agents

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C424S400000, C424S408000, C424S409000, C424S456000, C514S960000, C514S962000

Reexamination Certificate

active

06372251

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. U.S. Pat. No. 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 granulate thus produced is 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.
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)acylate 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. No. 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 pravastatin, 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 semi-solid formulation comprising a lipid-regulating agent, a liquid component, and a solid or semi-solid component.
Said formulation is prepared by solubilizing said lipid-regulating agent in one or more liquid components to form a clear liquid solution, then solidifying said solution by adding one or more solid or semi-solid components to said solution to form a semi-solid formulation. Said formulation can melt or dissolve upon mixing with a bulk aqueous medium. The resulting formulation results in an increase in drug solubility and oral bioavailability, and an improved dissolution rate.
The formulation may be administered directly, diluted into an appropriate vehicle for administration, encapsulated into soft or hard gelatin capsules for administration, or administered by other means obvious to those skilled in the art.


REFERENCES:
patent: 4058552 (1977-11-01), Mieville
patent: 4739101 (1988-04-01), Bourgogne et al.
patent: 4800079 (1989-01-01), Boyer
patent: 4895726 (1990-01-01), Curtet et al.
patent: 4925676 (1990-05-01), Ghebre-Sellassie et al.
patent: 4927639 (1990-05-01), Ghebre-Sellassie et al.
patent: 4957746 (1990-09-01), Valducci
patent: 4961890 (1990-10-01), Boyer
patent: 5030447 (1991-07-01), Joshi et al.
patent: 5180589 (1993-01-01), Joshi et al.
patent: 5380745 (1995-01-01), Uomoto et al.
patent: 5545628 (1996-08-01), Deboeck 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: 5827536 (1998-10-01), Laruelle
patent: 5880148 (1999-03-01), Edgar et al.
patent: 6180138 (2001-01-01), Engh et al.
patent: 0793958 (1997-02-01), None
patent: 0 998 927 (1999-10-01), None
patent: 1 590 864 (1981-06-01), None
patent: 8201649 (1982-05-01), None
patent: WO 92/10996 (1992-07-01), None
patent: WO 95/24893 (1995-09-01), None
patent: WO 98/15264 (1998-04-01), None
patent: 99/29300 (1999-06-01), None
patent: WO 99/36060 (1999-07-01), None
patent: 99/36060 (1999-07-01), None
patent: 00/37057 (2000-06-01), None
Ming-Thau Sheu et al., Characterization and Dissolution of Fenofibrate Solid Dispersion Systems,International Journal of Pharmaceutics, (1994), vol. 103, pp. 137-146.
G. F. Palmieri et al., Characterization and Dissolution Studies of PEG 4000/Fenofibrate Solid Dispersions,S.T.P. Pharma Sciences, (1996), pp. 188-194.
A. Ben-Amor et al., Augmentation De La Biodisponibilite D'Un Agent Hypolipemiant Par Incorporation Dans Une Gelule A Contenu Liquide, Labaratoire de Pharmacie Galenique, Section de Pharmacie, Universite de Geneve, Sciences II, 30 Quai Ernest Ansermet, 12111 Geneve 4, Suisse.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

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.

Rate now

     

Profile ID: LFUS-PAI-O-2822692

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.