Coating processes – Particles – flakes – or granules coated or encapsulated – Fluidized bed utilized
Reexamination Certificate
2000-06-06
2002-06-18
Barr, Michael (Department: 1762)
Coating processes
Particles, flakes, or granules coated or encapsulated
Fluidized bed utilized
C427S214000, C424S001130, C424S001290, C424S460000, C424S491000
Reexamination Certificate
active
06406745
ABSTRACT:
BACKGROUND OF THE INVENTION
A. Field of the Invention
The invention relates to methods of coating particles, and the particles produced thereby. More specifically, the invention relates to drug particles or drug delivery particles coated with a material, which may be biodegradable or biocompatible, such as a polymer. The coating may impart a number of characteristics to the particle, including altering its surface properties, its rate of dissolution, or its rate of diffusion and/or release of an active component. More particularly, the invention provides methods for preparing particulate compositions that are coated with ultrafine layers of coating materials, preferably organic polymeric coating materials, applied through a non-aqueous, non-solvent technique. A particularly preferred process is a vapor deposition process such as pulsed laser ablation. Among the many advantages of the disclosed methods are control of both the thickness and uniformity of the coating on the surfaces of the selected particulate drug.
Description of Related Art
B. Pharmaceutical formulations that provide for delivery of a drug over an extended period of time have revolutionized the pharmaceutical industry. Whether the delivery is sustained, modified, controlled, extended, or delayed, the concept is generally the same—provide in a single dose what previously required multiple doses. (“Sustained release” will be used herein to describe this generic class of release mechanisms.) The desire is to provide an effective concentration of the drug for an appropriate length of time.
There are several advantages to such formulations. For example, having a lower concentration of the drug in the body for a longer period of time lowers the incidence of toxicity for drugs with a narrow therapeutic window, and often improves the overall effect. Also, patient compliance is improved when the dosing regimen is decreased; a patient is far more likely to take a single daily dose, than to take two, three, or even four doses daily. This is true for drugs delivered orally, as well as those which are injected, inhaled, or delivered by transdermal or transmucosal diffusion.
Traditionally, sustained release has been achieved by placing a coating material over the drug particles or granules. Thus, tablets, capsules, caplets, pills, and other formulations with coated granules have been provided. Depending on the desired drug release properties, a drug core may be coated with a single layer of coating, or alternating coatings may be provided, or the drug may actually be interdispersed within a coating material. The possibilities are numerous, and the particulars of the formulation are chosen based on the desired drug release properties. A summary of such formulations is provided in
Modern Pharmaceutics
, Second Edition, edited by Gilbert S. Banker and Christopher T Rhodes, the entire contents of which is hereby incorporated by reference.
Oral and other sustained release delivery systems have largely been based on solvent-based particulate or matrix-type systems. These systems utilize spray-coating or mechanical mixing of a core drug particle and/or excipient granule with a polymer, e.g., a cellulose, polyacrylate, degradable polyester, etc., to control the rate of release of the active drug substance. In addition, traditional matrix systems may contain a gel-forming excipient, e.g., polyvinyl alcohol (PVA), polyethylene oxide (or polyethylene glycol, PEG), celluloses, etc., that form a gel layer after delivery that releases the drug over time by diffusion of the drug through the matrix. A limitation of these systems is that multi-stage scale-up from the laboratory to commercial-scale production of formulations can be lengthy and difficult, often requiring specialized equipment and expensive solvents. Additionally, known systems produce formulations that have a relatively high concentration of polymer, thick coatings, and tend not to be reproducibly manufactured with identical release profiles.
Therefore, what is needed are improved methods for preparing coated drug particles that do not suffer these limitations, and that are useful in preparing pharmaceutical formulations with superior drug delivery and efficacy properties.
Summary of the Invention
B. Features and Advantages of the Invention
The present invention overcomes these and other inherent deficiencies in the prior art by providing novel coating methods for use in preparing coated particles, and in particular, coated drug particles for having improved pharmaceutical properties. In general, the methods disclosed herein provide a means for coating particulate materials with one or more layers of discrete coating matter or materials such that the coated matter or materials adheres generally uniformly to the surface of the particulate materials to form either continuous or discontinuous coatings depending upon the particular application of the coated particulate materials.
The invention also provides for modification of (1) the aggregation characteristics; (2) the flow properties; and (3) the release-rate of the drug, by applying coatings using the methods of the present invention to greatly enhance the pharmacokinetic profiles of coated drugs.
Additional advantages include improved flow properties during manufacture; and formulation stability, e.g., shelf-life.
Drugs coated by the processes outlined herein have been shown to possess high encapsulation efficiencies (>99% drug) while requiring minimal processing. The process also has several advantages over current coating techniques including:
1. It is a fast process with modification times (i.e., how long it takes to coat a particulate from beginning to end) on the order of minutes.
2. A variety of materials can be used for producing the coatings on the particulate materials, thus it is possible to produce films from materials with proven biocompatibility.
3. It can be a dry, solventless technique conducted under a sterile environment, which is an important consideration in the drug industry.
4. Particle agglomeration/adhesion can be minimized by applying coatings that affect the bonding nature and electrostatic charge on the surface of the particulate materials.
5. Formation of microcapsules by depositing coatings onto the particle surface will make it possible to control drug release kinetics by: (a) diffusion of the drug through the polymer; (b) degradation of the biodegradable polymer coating off of the drug particles, thereby releasing the core drug material.
6. Laser ablation can be performed under normal atmospheric pressure, as opposed to a vacuum, thereby eliminating the need for vacuum mechanisms, including chambers and pumps, in the process, and allowing for a continuous production line. This advantage significantly improves production times, and thereby decreasing production costs and scale-up difficulty.
SUMMARY OF THE INVENTION
The present invention provides methods of coating core materials comprising: providing target materials and core materials; ablating the target materials to form ablated particulate target materials; and coating the core materials with the ablated particulate target materials; wherein the method occurs at a pressure of about 10 Torr or higher. The ablating may occur at a pressure of about 20 Torr or higher, including about 760 Torr.
The core materials may have an average diameter of about 0.5 &mgr;m to about 1 mm. Coating the core materials with the ablated particulate target material may result in a coating of the target materials on the core materials of a thickness of less than about 1000 nm. The coating on the core materials may have a thickness of less than about 100 nm, or less than about 10 nm.
Coating the core materials with the ablated particulate target materials may result in coated particles having average diameters of less than about 1 mm, less than about 100 &mgr;m, or less than about 10 &mgr;m. Preferably, the target materials include at least a biodegradable polymer, biocompatible polymer, polysaccharide, and/or protein.
Ablating may be achieved by the use of a hig
Barr Michael
Blanton Rebecca
Finnegan Henderson Farabow Garrett & Dunner
Nanosphere Inc.
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