Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1998-09-18
2004-02-17
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S464000, C424S465000, C424S451000, C424S435000, C424S490000, C514S772300, C514S784000, C514S785000, C514S786000, C514S951000, C514S770000
Reexamination Certificate
active
06692767
ABSTRACT:
The present invention relates to the field of pharmaceutical delivery formulations and, more particularly, to those providing rapid release of the therapeutic agent upon oral delivery.
BACKGROUND OF THE INVENTION
A variety of methods for forming micropellets are known in the art. See Kennedy and Niebergall, Development and Optimization of a Solid Dispersion Hot-Melt Fluid Bed Coating Method, Pharmaceutical Development and Technology, 1(1):51-62(1996); Hincal and Kas, Preparation of Micropellets by Spray Congealing, in Multiparticulate Oral Drug Delivery, Ghebre-Sellassie (Ed.), Marcel Dekker, Inc. NY, pgs. 17-34 (1994); Eldem et al., Polymorphic of Sprayed Lipid Micropellets and its Evaluation by Differential Scanning Calorimetry and Scanning Electron Microscopy, Pharmaceutical Research, 8(2):178-184 (1991); Eldem et al., Optimization of Spray Dried and -Congealed Lipid Micropellets and Characterization of Their Surface Morphology by Scanning Electron Microscopy, Pharmaceutical Research, 8(1):47-54 (1991); and Deasy, Spray Drying, Spray Congealing, Spray Embedding and Spray Condensation, in Microencapsulation and Related Drug Processes, Marcel Dekker, Inc., NY, pgs. 181-193 (1984).
SUMMARY OF THE INVENTION
In accordance with an aspect of the present invention, there is provided a composition including at least one therapeutic agent and a pharmaceutically acceptable carrier in the form of a solid beadlet wherein the beadlet includes a acceptable carrier in the form of a solid beadlet wherein the beadlet includes a combination of at least one hydrophobic long chain fatty acid or fatty acid ester and at least one surfactant. The hydrophobic long chain fatty acid or ester thereof and surfactant are present in the beadlet as a solid solution. The therapeutic agent is dispersed in the solid beadlet and is present in the composition in a therapeutically effective amount, with such amount generally being at least 0.001%, by weight, of the composition.
The hydrophobic long chain fatty acid or ester thereof is generally present in an amount of at least 20% with such material in most cases being present in an amount no greater than 97%, by weight.
The beadlet(s) generally has a particle size that does not exceed 1000 microns. In most cases, the particle size is at least 50 microns. In one embodiment, the particle size does not exceed 500 microns. In another embodiment, the particle size is from 100 to 350 microns.
In a preferred embodiment, the surfactant is one that is liquid at room temperature in that a liquid surfactant in the composition of the invention provides for improved drug delivery.
The surfactant may comprise at least 3% of the core beadlet formulation and in many cases exceeds 10% of the core beadlet formulation all by weight.
The beadlet is preferably in the form of a solid solution wherein the therapeutic agent is dissolved in the hydrophobic material.
In one aspect, the invention provides a solid solution beadlet (used synonymously with granule or particle) comprising (i) at least about 20% by weight of a hydrophobic long chain fatty acid or ester material; (ii) from about 3% to about 40% by weight of a surfactant; and (iii) from about 1% to about 70% by weight of a therapeutic agent, which in admixture form a solid solution at room temperature.
The long chain acids used as an acid or ester generally include at least 12 carbon atoms and generally do not include more than 22 carbon atoms. The acids may be saturated or unsaturated and generally are aliphatic long chain acids. When used as an ester, the ester is preferably a glycerol ester. The ester may be a mono-, di or tri-ester of glycerol.
The hydrophobic material is preferably oleic acid, gadoleic acid, eurcic acid, linoleic acid, linolenic acid, ricinoleic acid, riachidonic acid, glycerol esters of the foregoing acids, or glycerol behenate.
The hydrophobic material preferably has a melting point of from about 40 to about 150° C., and is most preferably glyceryl behenate (e.g. Compritol™ from Gattefosse Inc., France). The surfactant is preferably selected from the group consisting of polyglycolyzed glycerides, polyoxyethylene sorbates, ethylene or propylene block copolymers or combinations thereof, and is most preferably polyoxyethylene 20 sorbitan monolaurate or Labrasol®, a polyglycolized glyceride (Gattefosse, France). The beadlet can further include sodium C
9
-C
30
alkyl sulfate or citric acid. The beadlet can also contain a glidant (such as fumed silicon dioxide) to improve tabletting properties. Typically preferred therapeutic agents include acyclovir, acyclovir and at least one additional antiviral agent, dihydroergotamine or methylphenidate.
In another preferred embodiment the beadlets are coated with an immediate release coating, such as Opadry®I (hydropropylmethylcellulose, i.e., HPMC) and Opadry®-II (HPMC, maltodextrin and propyleneglycol) from Colorcon, Inc. (West Point, Pa.) or Aquateric® (cellulose acetate phthalate enteric polymer) from FMC, Inc. (Philadelphia, Pa.).
Another embodiment provides pharmaceutical compositions of a plurality of coated or uncoated single phase solid solution beadlets in a pharmaceutically acceptable carrier. The composition can be, for example, in the form of a tablet (optionally coated, such as with an enteric coating), buccal tablet, sublingual tablet, capsule or other oral dose delivery forms.
The oral delivery form can also be coated, if desired, with various protective coating materials or with materials that control the rate or location of release in the patient. This can be done by known methods using such known materials.
REFERENCES:
patent: 3857933 (1974-12-01), Ross et al.
patent: 4880634 (1989-11-01), Speiser
patent: 5213810 (1993-05-01), Steber
patent: 5340588 (1994-08-01), Domb
patent: 5430021 (1995-07-01), Rudnic et al.
patent: 5807583 (1998-09-01), Kristensen et al.
patent: 448930 (1991-10-01), None
patent: 11-502201 (1999-02-01), None
patent: 91/07171 (1991-05-01), None
patent: 94/12180 (1994-06-01), None
patent: 94/27557 (1994-12-01), None
Deasy, Patrick B., “Spray Drying, Spray Congealing, Spray Embedding, and Spray Polycondensation,”Microencapsulation and Related Drug Processes,Marcel Dekker, Inc. NY:181-193 (1984).
Eldem, et al., “Optimization of Spray-Dried and -Congealed Lipid Micropellets and Characterization of Their Surface Morphology by Scanning Electron Microscopy,”Pharmaceutical Research, 8(1):47-54 (1991).
Eldem, et al., “Polymorphic Behavior of Sprayed Lipid Micropellets and Its Evaluation by Differential Scanning Calorimetry and Scanning Electron Microscopy,”Pharmaceutical Research, 8(2):178-184 (1991).
Hincal, A.A. and Kas, H. S., “Preparation of Micropellets by Spray Congealing,”Multiparticulate Oral Drug Delivery Ghebre-Sellassie(Ed.),Marcel Dekker, Inc. NY:17-34 (1994).
Kennedy, J.P. and Niebergall, P.J., “Development and Optimization of a Solid Dispersion Hot-Melt Fluid Bed Coating Method,”Pharmaceutical Development and Technology, 1(1):51-62 (1996).
Burnside Beth A.
Couch Richard A.
Guo Xiaodi
McGuinness Charlotte M.
Rudnic Edward M.
Lane Mary Elisa
Shire Laboratories Inc.
Spear James M.
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