WO2008002601A1

WO2008002601A1 - Process for coating a substrate

Info

Publication number: WO2008002601A1
Application number: PCT/US2007/014896
Authority: WO
Inventors: Ingo Scheer
Original assignee: Ingo Scheer
Priority date: 2006-06-27
Filing date: 2007-06-26
Publication date: 2008-01-03
Also published as: US7892593B2; US20080286440A1; DE112007001479T5

Abstract

A method to coat a substrate for the formation of coatings having a desired surface morphology is provided, wherein the roughness and the total surface area of the coating can be varied during the coating process. The method of the present invention comprises the steps of generating droplets from a coating composition, transporting the droplets to the substrate and depositing the droplets on the substrate.

Description

INVENTION TITLE Process for coating a substrate.

CROSS-REFERENCE TO RELATED APPLICATIONS This Application relates to and claims priority from commonly owned U.S. Patent Application Serial No. 11/476,493, filed on June 27, 2006.

FEDERALLY SPONSORED RESEARCH

Not Applicable

SEQUENCE LISTING OR PROGRAM

Not Applicable

BACKGROUND OF THE INVENTION The present invention relates to an apparatus and method for applying a coating to at least a portion of a substrate having desired surface properties. In particular, the invention relates to a method for producing polymer coatings with various morphologies on medical implants like stents.

Coatings are often applied to medical implants such as pacemakers, vascular grafts, catheters, stents, heart valves, tissues or sensors to have desired effects and increase their effectiveness. These coatings may deliver a therapeutic agent to the lumen that reduces smooth muscle tissue proliferation or restenosis and may comprise a polymer carrier. Furthermore, implants may be coated to improve surface properties such as lubriciousness, to achieve enhanced biocompatibility and to control the timing and rate of release of the therapeutic agent being delivered. Balloon delivery systems, stent grafts and expandable stents are specific examples of implants that may be coated and inserted within the body. Stents such as described in U.S. Pat. No. 4,733,665 are tiny, expandable mesh tubes supporting the inner walls of a lumen used to restore adequate blood flow to the heart and other organs.

Such coatings have been often applied to the surface of an implant by spray coating. An atomizing device including an orifice and an internal fluid passage leading to said orifice is typically placed perpendicular to the longitudinal axis of the substrate to be coated. The droplets 52 generated by the atomizing device are expelled through the orifice and the majority of the droplets hit the surface of the substrate 54 at an impact angle of approximately θ=90 degrees with a comparatively high impulse force resulting in a dense coating splat 53 as shown in FIG. 1A.

The comparatively high coating compaction of the produced coating may however result in an inhomogeneous coating thickness and cracks. In addition, it may be difficult to produce porous coatings, which can be used in medical implants as reservoirs for the retention of therapeutic agents and may be desirable to enhance tissue ingrowth and tissue healing. Also, conventional coating methods may not allow changing the morphology of the coating layer instantaneously which can be desirable to accommodate the need for different elution profiles as may be required by the medical application.

OBJECT OF THE INVENTION

Accordingly, there is a need for a flexible way of coating medical implants so that a desired surface morphology can be produced to accommodate the need for different elution profiles and/or therapeutic agents. The main object of the invention is to provide a cost-effective and flexible method to form a polymer coating on a substrate having desired surface properties in terms of surface texture, roughness and surface area.

A further object is to provide a homogeneous coating thickness on the entire surface and particularly on hard to reach areas of the medical implant, in order to improve the quality and integrity of the coating. Another object is to allow immediate adjustment of coating properties so that a variable coating thickness and morphology along the surface of the substrate can be produced.

It is still another object to increase porosity and surface area of the coating. These and additional features and advantages of the invention will be more readily apparent upon reading the following description of exemplary embodiments of the invention and upon reference to the accompanying drawings herein.

. BRIEF SUMMARY OF THE INVENTION

The method of the invention provides a process for the formation of coatings having an improved quality and a desired surface morphology. The coatings may include a polymer carrier and a therapeutic substance. Coatings formed by the process of the invention can be designed to exhibit different properties according to the particular requirements. For example, the porosity, the roughness and the total surface area of the coating can be varied during the spray run. The mass diffusion rates through the surface may be controlled by either increasing or decreasing the surface area of the coating and the porosity in the process of the present invention. Thus, the surface area and porosity may be varied to provide selective coating properties of the coating layer along the surface of the substrate.

The process of the present invention comprises the steps of generating droplets from a coating composition, transporting the droplets to the substrate so that the majority of the droplets have a tangential velocity component in relation to the surface of the substrate, and depositing the droplets on the substrate with an impact angle other than 90 degrees to form a coating layer. The droplets may be deposited at an impact angle between 30 and 85 degrees so that a textured coating is obtained. The droplet generation and/or transportation process may be controlled to provide selective surface properties by changing the impact angle of the generated droplets, wherein the impact angle is defined as the angle between the direction vector of the droplet and the surface of the substrate. 75

SUMMARY

In one embodiment of the present invention, a method to apply a coating to a medical implant using an atomizer to disintegrate a coating solution comprising a therapeutic agent into droplets is provided. The atomizer is tilted in relation to the surface of the medical implant. The method comprises the steps of

80 disintegrating the coating solution into droplets, transporting the droplets to the medical implant so that the majority of the droplets have a tangential velocity component in relation to the surface of the medical implant and depositing the droplets with an asymmetric splat morphology on the medical implant to form a coating. The method may further comprise the step of changing the tilt angle between the spray axis and the surface of the medical implant during the coating process in order to vary the morphology of the coating layer. In one

85 or more embodiments, the medical implant may be a stent.

In another embodiment, a method to apply a coating to a medical device, using means to disintegrate a coating composition into droplets and means to generate a vortical gas flow field having a swirl intensity between 0.01 and 2.5 to transport the droplets to the medical implant, is provided. The method comprises the steps of disintegrating the coating composition into droplets, transporting the droplets in said gas flow field to

90 the medical device so that the majority of the droplets have a tangential velocity component in relation to the surface of the medical device and depositing the droplets on the medical device.

In one or more embodiments, the method may further comprise the step of changing the swirl intensity during the coating run in order to vary the morphology of the coating along the surface of the substrate. The coating composition may be disintegrated by the vortical gas flow field. The means to generate the vortical gas flow

95 field can comprise a conduit with at least a first and a second gas inlet, wherein swirl motion is induced in the gas flow through at least one gas inlet. The swirl intensity may be changed by adjusting the ratio between the axial gas flux of swirl momentum and the axial gas flux of axial momentum. In one or more embodiments, the medical device may be a stent and the coating composition may comprise a therapeutic agent and/or may include pores.

100 In yet another embodiment, a method to apply a coating to a medical device using means having at least one exit aperture to generate droplets from a coating composition and suction means to generate a gas flow field including at least one entrance aperture is provided. The medical device is positioned between said exit aperture and said entrance aperture. The method comprises the steps of disintegrating the coating composition into droplets, generating a gas flow field to direct the droplets to the substrate so that the majority 105 of the droplets comprise a tangential velocity component in relation to the surface of the medical device and depositing the droplets on the medical device with an impact angle other than 90 degrees. In one or more embodiments, the droplets are formed through vibration or electrostatic energy and the medical device may be a stent. Furthermore, the entrance aperture may be tilted in relation to the spray axis. The tilt angle of the entrance aperture can be changed during the application of the coating to vary the 110 morphology of the coating. Also, the entrance aperture of the suction means may be positioned at an offset distance from the spray axis of the droplet generating means and the position of the entrance aperture can be changed during the application of the coating to vary the morphology of the coating. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

115 The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate the embodiments of the present invention and together with the description, serve to explain the principles of the invention. In the drawings:

FIG. 1 A (Prior Art) is a schematic representation of an droplet impact onto a substrate with a normal impact angle (90 degrees);

120 FIG. 1B is a schematic representation of a droplet impact onto a substrate at an angle smaller than

90 degrees;

FIG. 2 is a flow chart of the coating method of the present invention; FIG. 3 is a spray coating setup of a substrate (atomizer tilted with respect to substrate); FIG. 4 is a is a spray coating setup of a substrate (suction device positioned at an offset distance with 125 respect to atomizer);

FIG. 5 is a Computational Fluid Dynamics (CFD) simulation of a stent coating process visualizing the droplet trajectories (suction device positioned at an offset distance/angle with respect to atomizer);

FIG. 6 is a spray coating setup of a substrate comprising a vortical flow (atomizer positioned perpendicular to substrate);

130 FIG. 7A is a cross sectional view of a twin-fluid atomizer having radial and tangential gas inlets;

FIG. 7B is a perspective view of the gas conduit of the atomizer of FIG. 7 A; FIG. 8 is a diagrammatic representation of an exemplary coating setup; FIG. 9 is a portion of a screen dump of the software used to control the swirl intensity; FIG. 10 is a spatial droplet distribution of a spray pattern at a swirl intensity of 0.3; 135 FIG. 11 A is a SEM image of a portion of a stent at a swirl number of 0;

FIG. 11 B is a SEM image of a portion of a stent at a swirl number of 0.3; FIG. 11C is a SEM image of a portion of a stent at a swirl number of 0.6; FIG. 12A is a SEM image (magnification 15Ox) showing the surface morphology of a portion of a stent;

140 FIG. 12B is a SEM image (magnification 1000x) showing the surface morphology of a portion of a stent; and

FIG. 12C is a SEM image (magnification 1000Ox) showing the surface morphology of a portion of a stent. DETAILED DESCRIPTION

145 Further aspects of the invention will become apparent from consideration of the drawings and the ensuing description of preferred embodiments of the invention. A person skilled in the art will realize that other embodiments of the invention are possible and that the details of the invention can be modified in a number of respects, all without departing from the inventive concept. Thus, the following drawings and description are to be regarded as illustrative in nature and not restrictive. Further features and advantages of the present

150 invention, as well as the structure and operation of various embodiments of the present invention, are described in detail below with reference to the accompanying drawings.

Referring now to FIG.2, the method to apply a coating layer to a substrate, such as a stent, having a desired roughness and porosity comprises the steps of generating droplets from a coating composition, transporting the droplets to the substrate so that the majority of the droplets have a tangential velocity

155 component in relation to the surface of the substrate and depositing the droplets on the substrate with an impact angle other than 90 degrees. The droplet generation and transportation step can be controlled as described in detail in FIG. 8 to fine tune the surface properties of the substrate to be coated.

The substrate is preferably an implant and may include pacemakers, vascular grafts, catheters, stents, heart valves, tissues, sensors and the like.

160 The coating composition may comprise one or more a solvents, one or more polymers, and/or one or more therapeutic substances. The therapeutic substance may include, but is not limited to, proteins, hormones, vitamins, antioxidants, DNA, antimetabolite agents, anti-inflammatory agents, anti-restenosis agents, anti-thrombogenic agents, antibiotics, anti-platelet agents, anti-clotting agents, chelating agents, or antibodies. Examples of suitable polymers include, but are not limited to, synthetic polymers including

165 polyethylen (PE), poly(ethylene terephthalate), polyalkylene terepthalates such as poly(ethylene terephthalate) (PET), polycarbonates (PC), polyvinyl halides such as polyvinyl chloride) (PVC), polyamides (PA), poly(tetrafluoroethyleπe) (PTFE), poly(methyl methacrylatβ) (PMMA), polysiloxanes, ethylene-vinyl acetate (EVAc), polyurethane, and poly(vinylidene fluoride) (PVDF); biodegradable polymers such as poly(glycolide) (PGA), poly(lactide) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(anhydrides); or

170 natural polymers including polysaccharides, cellulose and proteins such as albumin and collagen. The coating composition can also comprise active agents, radiopaque elements or radioactive isotopes. The solvent is selected based on its biocompatibility as well as the solubility of the polymer. Aqueous solvents can be used to dissolve water-soluble polymers, such as Poly(ethylene glycol) (PEG) and organic solvents may be used to dissolve hydrophobic and some hydrophilic polymers. Examples of suitable solvents include methylene

175 chloride, ethyl acetate, ethanol, methanol, dimethyl form amide (DMF), acetone, acetonitrile, tetrahydrofuran (THF), acetic acid, dimethyle sulfoxide (DMSO), toluene, benzene, acids, butanone, water, hexane, and chloroform. For the sake of brevity, the term solvent is used to refer to any fluid dispersion medium whether a solvent of a solution or the fluid base of a suspension, as the invention is applicable in both cases.

180 FIG. 1 B is a schematic of a droplet impact on a substrate according to the method of the present invention. The impact velocity V of the droplet 52 comprises a normal velocity component VN and a tangential velocity component VT resulting in an impact angle θ other than 90 Degrees between droplet and substrate surface. The tangential velocity component VT promotes droplet spreading over the substrate 54 rather than impacting on it. An asymmetric splat morphology is expected to occur because VT contributes to the spreading of unsolidified materials toward point a. If the spray angle is decreased, especially for σ less than 45 degrees, and the tangential velocity component W is increased, porosity and roughness of the coating increase.

In one exemplary embodiment as shown in FIG.3, atomizer 1 is tilted in relation to the substrate so that the spray angle σ between the spray axis 51 and the surface of the substrate is less than 90 degrees. A twin-fluid atomizer is preferably used to disintegrate the liquid to be atomized. In operation, liquid is supplied to the liquid inlet, travels through the liquid path and exits the atomizer orifice. Gas, which is fed in the gas inlet, breaks up the liquid into fine droplets when it exits the gas orifice and directs the droplets to the substrate. By tilting the atomizer in relation to the substrate, droplets having a tangential velocity component in relation to the surface of the substrate are deposited on the substrate 54 at an impact angle θ of less than 80 degrees.

Although a twin-fluid atomizer, such as depicted in FIG. 7, is preferably used in this embodiment, it is to be understood that the principles of the present invention may be applied to other nozzle types and geometries as well, including atomizers that employ electrostatic or ultrasonic energy, for example. Dispensing and atomization systems incorporating multiple nozzles and/or atomizer assemblies of a single configuration or differing configurations may incorporate the principles of the present invention.

In order to change the surface properties such as roughness and porosity of the coating layer, the impact angle θ of the droplets may be varied during the coating process by increasing or decreasing the angle α between spray axis 51 of the atomizer and substrate 54.

The following exemplary embodiment is suitable if a coating having a comparatively low compaction and an increased porosity is desired. The droplet impulse and compaction of the coating layer is minimized by generating a low droplet velocity of preferably less than 5 m/s and a comparatively small droplet size. Referring to FIG. 4, an ultrasonic atomizer 1, an entrance aperture of a suction device 55 and a substrate 54 located therebetween are depicted. The atomizer 1 is positioned above the substrate and located perpendicular relation to the surface of the substrate. Alternatively, the atomizer may be tilted. The entrance aperture of the suction device 55, which is preferably provided underneath the substrate, has an offset distance d from the spray axis 51. To increase the efficiency of the coating process the entrance aperture of the suction device may be tilted towards atomizer 1. The suction device may comprise an ejector or fan, which is connected to the entrance aperture of the suction device 55 and having a suction capacity ranging from 5 to 25 l/min. In operation, a coating composition is supplied to the ultrasonic atomizer and is broken-up into fine droplets at an operation frequency of approximately 130 kHz. Droplets having a size of less than 20 μm and comparatively low droplet velocities of less than 5 m/s are produced in the proximity of the liquid orifice. The generated droplets are transported from the atomizer orifice to the substrate 54 by gravity and/or by the gas stream produced by the suction device. By positioning the entrance aperture of the suction device 55 at an off 220 centered position at a distance dfrom the spray axis, tangential velocity components are generated in relation to the substrate 54 and the majority of the transported droplets 52 are deposited under an impingement angle other than 90 degrees. The impingement angle may be changed during the coating process by altering the position or the tilt angle of the entrance aperture of the suction device. The coating properties in terms of roughness and porosity can be therefore varied along the surface of the substrate.

225 FIG.5 is a Computational Fluid Dynamics (CFD) simulation of a droplet transport and deposition process on a stent. The volume model consists of an atomizer orifice 1, an entrance aperture 55 of a suction device and a stent 54 placed therebetween. The stent is supported by a holding device and located approximately 15 mm downstream from the atomizer orifice. The entrance aperture 55 of the suction device is placed at a distance of approximately 8 mm from the stent. The atomizer may also be tilted towards the

230 entrance aperture to improve the efficiency of the process. The trajectories 56 were simulated for droplets having a diameter of approximately 18 μm. The droplets are transported from the atomizer orifice to the stent by gravity and by the gas flow field generated by the suction device. In order to direct the droplets to the stent and to deposit them at an impingement angle other than 90 degrees a suction with a flow rate of 10 l/min was generated. Depending on the size of the substrate and the position of the entrance aperture, the suction

235 capacity may vary between 5 and 25 l/min. A second low velocity gas flow field may be produced at the atomizer orifice to improve process stability and to prevent deflection of the droplets, which may be caused by the air flows within the coating chamber.

A further exemplary embodiment of the present invention is depicted in FIG. 6. Atomizer 1 is preferably located perpendicular to the surface of the substrate 54. Droplets are generated from a coating

240 composition and a gas flow field comprising a vortex is produced to direct the generated droplets to the substrate 54. Various atomizers including, but not limited to, devices employing pneumatic, electrostatic or ultrasonic energy may be used to disintegrate the fluid to be atomized. Such devices may also comprise means to generate a gas flow field with a vortex.

Referring to FIG. β, an exemplary coating setup comprising atomizer, liquid and gas supply,

245 proportion valves and flow meter arrangements for axial and tangential gas flow are provided.

By way of example, the twin-fluid atomizer of FIG. 7 is used to atomize a liquid composition and to generate a gas flow field with a vortex through pressurized gas, provided, for example, by a compressor or by a pressurized container. Atomizer 1 comprises a liquid path extending from liquid inlet 9 to liquid orifice 15. The pressurized gas is fed through gas inlets 21 and 22 into gas conduit 6 having a radius ro and expelled

250 through annular gap 16 having a radius R. A perspective view of gas conduit 6 depicting the position of the two inlets 21 for axial gas flow and the two tangential gas inlets 22 used to induce swirl motion into the axial gas flow is shown in FIG.7B.

As shown in FIG. 8, the spray axis of the atomizer is located perpendicular to the surface of the substrate and positioned on the same plane. The distance between the atomizer tip and the substrate may

255 range between 10 and 60 mm and is preferably 20 mm. The liquid inlet of the atomizer is connected to a liquid supply source. A syringe pump may be used to feed the coating composition into the atomizer. The compressed gas is fed into valves, which regulate the axial and tangential gas flow. Gas mass flows (m axial, m tang) are measured, respectively, by means of a thermal mass flow meter.

A software, developed with LabView (Nl, Austin, TX, USA) by the inventor of the present invention, is

260 used to control the swirl intensity, the axial gas mass flow rate m axial and the tangential gas mass flow rate m tang. FIG. 9 is a portion of the Graphical User Interface of the control software displaying the current values for total flow, axial flow, tangential flow and swirl intensity. The swirl intensity of the gas can be varied instantaneously by regulating the axial and tangential gas ratio during the coating process. The impingement angle and the droplet trajectory can be thereby controlled to produce desired coating properties in terms of

265 roughness and porosity along the surface of the substrate.

The degree of swirl is described with non-dimensional criterion S- swirl intensity or swirl number defined as a number representing axial flux of swirl momentum G_β divided by axial flux of axial momentum G_x, multiplied by the nozzle radius R

270 S = ^G*

RG_x

The swirl intensity S is expressed by the following equation and obtained by integration of axial U and tangential W gas velocity profiles where r is the radial distance and p is the density.

To allow immediate control of the swirl intensity Sand the related tangential velocity component during the coating process, the swirl number can be related to the measured total gas mass flow rate m^and the tangential mass flow rate m_tøng. The value ro is the axial radius of the gas conduit in which the tangential 280 gas flow is introduced, R is the nozzle exit radius and A, is the total area of the two tangential inlets.

By controlling m_M and m^ng the swirl intensity S can be changed. In operation, the desired swirl 285 number and the total gas flow are entered by the operator. Axial gas mass flow is supplied through two symmetric inlets 21 and swirl motion is imparted to the annular flow by means of two tangential inlets 22. The gas flux comprising swirl motion is expelled through annular gap 16. A gas flow with an angular momentum is generated, resulting in a flow field with axial and tangential velocity components and increased shear forces at the atomizer orifice. The liquid flows through the liquid tube to the atomizing end, exits the liquid orifice 15 290 and is broken up by the atomizing air into very fine droplets having a tight droplet size distribution. By generating an angular momentum, an improved atom izat ion of the liquid and a stabilized spray with minimized pulsation is obtained. A homogeneous spatial droplet size distribution is produced as shown in FIG. 10.

Although some embodiments are shown to include certain features, the applicant specifically

295 contemplate that any feature disclosed herein may be used together or in combination with any other feature on any embodiment of the invention. It is also contemplated that any feature may be specifically excluded from any embodiment of an invention. Many variations of the invention will occur to those skilled in the art. Some variations include suction devices having different geometries, which are operated at various suction flow rates depending on the particular coating setup and on the shape of the coating target. Various atomizing

300 devices, such as single fluid nozzles, ultrasonic nozzles, electrostatic nozzles or twin-fluid nozzles, may be used to atomize the coating composition. They may also include means to support the droplet transportation and deposition process. All such variations are intended to be within the scope and spirit of the invention. The following examples are presented to illustrate the advantages of the present invention. These examples are not intended in any way otherwise to limit the scope of the disclosure.

305 Stents (manufactured by STI, Israel) having a diameter of 2 mm and a length of 20 mm were coated using two different polymer compositions. In example 1 the swirl intensity has been varied between 0 and 0.6 and in example 2 the swirl intensity was set to 0.3.

The stents were mounted on a holding device as described in US Pat. App. No. 60/776,522 incorporated herein as a reference. The atomizer of FIG.7 was used to disintegrate the coating composition

310 into fine droplets and apply the coating to the stents. Although a twin-fluid atomizer was used in the following examples, it is to be understood that the principles of the present invention may be applied to other atomizing devices as well. Dispensing and atomization systems incorporating multiple nozzles and/or atomizer assemblies of a single configuration or differing configurations may incorporate the principles of the present invention.

315 For best results, the atomizer may be aligned in relation to the stent so that the spray axis of the atomizer is perpendicular to the rotation axis of the stent and both axes are in the same plane. The atomizer orifice is preferably positioned at a distance of approximately 12 to 35 mm from the outer surface of the stent. The liquid inlet of the atomizer is connected to a liquid supply source. A syringe pump (Hamilton Inc., Reno, NV, USA) is preferably used to feed the coating substance to the atomizer. The compressed gas is fed

320 into valves, which regulate the axial and tangential gas flow. Gas mass flows (m axial, m tang) are measured, respectively, by means of a thermal mass flow meter (TSI, Shoreview, MN, USA).

The tangential component of velocity vt induced during the droplet generation and/or transportation process is responsible for the deposition of the droplets at an impact angle other than 90 degrees resulting in a coating having a desired roughness and porosity. It can be varied during the coating process by changing

325 the swirl intensity to allow a variable coating thickness along the surface of the substrate. A PC based controller is used to adjust the swirl intensity by regulating the axial gas mass flow rate m axial and the tangential gas mass flow rate m tang. The flow rate of the coating solution may range from about 0.5 ml/h to 50 ml/h. The atomizer can disintegrate the coating solution into fine droplets at an atomizing pressure ranging from about 0.3 bar to 330 about 1.5 bar. In order to achieve a fine atomization, the atomizer is preferably operated at a total gas flow rate of 6.2 l/min at 0.8 bar atomizing pressure.

Before exposing the substrate to the spray, it is important to make sure that the droplet generation and transportation process is stable. The spraying process may be monitored using an optical patternator in order to ensure that the spatial droplet distribution of the generated spray plume is in the desired limits as 335 described in US. Pat. App. No. 60/674,005 incorporated by reference herein.

During the application of the coating solution, rotary motion is transmitted to the stent to rotate the stent about its central longitudinal axis. The rotation speed can be from about 5 rpm to about 250 rpm. By way of example, the stent may rotate at 130 rpm. The stent is translated along its central longitudinal axis along the atomizer. The translation speed of the stent can be from about 0.2 mm/s to 8 mm/s. When applying the 340 coating solution, the translation speed is preferably 0.5 mm/s. The stent can be moved along the atomizer one time to apply the coating in one pass or several times to apply the coating in several passes. Alternatively, the atomizer may be moved one time or several times along the stent length.

The stents may remain mounted on the holding device to allow drying of the coating and subsequent inspection. One skilled in the art can appreciate that drying may be accomplished in a variety of ways based 345 on the coating formulation used.

EΞXAMPLE I

Several stents were coated according to the process of the present invention. A poly(vinylidene fluoride) PVDF HFP copolymer with a monomer composition of 80 % vinylidene fluoride and 10 % hexaflouropropylene (Solvay Advanced Polymers, Houston, TX, USA) was used to coat the stents. The

350 coating solution was prepared by dissolving the polymers in acetone, at five weight percent. Both the inside and the outside surfaces of the stents were coated. Care was taken so that the stents were coated at the same operating conditions. The swirl intensity was precisely adjusted to examine its influence on the resulting surface properties. Several scanning electron microscope (SEM) images were taken to visualize the surface morphology at different swirl intensities.

355 Stent #1 was coated at a swirl intensity of 0. The coating was applied according to the schematic representation of FIG. 1 A so that the majority of the droplets hit the surface at an impact angle of about 90 degrees. FIG. 11 A shows a portion of a coated stent having a smooth compacted coating with an inhomogeneous thickness around the struts due to an increased coating accumulation on the outer circumferential surface of the stent.

360 Stent #2 was coated at a swirl intensity of 0.3 according to the schematic representation of FIG. 1B.

FIG. 11 B depicts a portion of the coating having a homogeneous coating thickness covering the struts of the stent with a relatively smooth coating layer. Accumulation of excess material on the outer circumferential surface of the stent was not observed and the coating looked uniform. Compared to stent #1 the coating seems more homogeneous especially on the outer circumferential surface and at the side faces of the struts

365 and an increased roughness of the surface is visible. Stent #3 was coated at a swirl intensity of 0.6 according to the schematic representation of FIG. IB. FIG. 11C illustrates a portion of a stent having a homogeneous thickness at the outer surface and at the side faces of the struts. Accumulation of excess material on the outer circumferential surface of the stent was not observed and the coating looked uniform. Compared to stent #1 and #2 an increased surface roughness and

370 surface area is visible.

The difference between these stents is the thickness of the coating, with the coating on stent #1 being the thickest and with an inhomogeneous coating accumulation on the outer circumferential surface of the stent. The coating seems to be more homogeneous in terms of thickness with increased swirl numbers. In addition, the morphology in terms of roughness changes and a substantially increased surface area is noted

375 at relatively high swirl intensities. Inducing a tangential velocity component in the gas stream by increasing the swirl intensity seems to improve process stability. This may result from an improved droplet break up and mixing of the coating composition leading to a more homogeneous droplet distribution. It was also observed that increased swirl intensities might prevent clogging of the atomizer.

380 EXAMPLE Il

Several stents were coated according to the process of the present invention using the poly(tetrafluoroethylene) dispersion PTFE 307A (DuPont, Wilmington, DE, USA). The dispersion contains approximately 60% (by total weight) of 0.05 to 0.5 μm c resin droplets suspended in water and approximately 6% (by weight of PTFE) of a nonionic wetting agent and stabilizer. Both the inside and the outside surfaces of 385 the stents were coated. The stents were coated at a swirl intensity of 0.3 according to the schematic representation of FIG. 1B. FIGS. 12A-C are scanning electron microscope (SEM) images of the coating morphology produced on a stent according to the process of the present invention.

Referring to RG. 12A, a stent having a homogeneous coating with a comparatively large surface area and roughness is shown. Accumulation of excess material on the surface of the stent was not observed and 390 the coating looked uniform.

To better visualize the morphology of the coating two further SEM images were taken. In FIG. 12B a small portion of the stent having an increased surface roughness and surface area is depicted at a magnification of 100Ox. In addition, the image reveals the presence of pores.

FIG. 12C shows the portion of the stent at a magnification of 1000Ox to better visualize the 395 moφhology of the coating and to show the pores in more detail.

The different types of coatings exhibit a variety of properties with respect to the surface area, porosity and thickness of the coating. It has been found that the surface properties can be varied during the process by controlling the impact angle of the droplets with respect to the substrate to be coated. A more homogeneous coating having increased surface area, roughness and porosity can be obtained by increasing 400 the tangential velocity component of the droplets. In contrast, when spraying higher viscosity polymer compositions without inducing a tangential velocity component the coating tends to accumulate at the outer circumferential surface of the stent which may result in coating defects such as webbing and peeling.

Claims

CLAIMSWhat is claimed is:

1. A method to apply a coating to a medical implant using an atomizer to disintegrate a coating solution comprising a therapeutic agent into droplets, wherein the atomizer is tilted in relation to the surface of the medical implant, comprising the steps of: disintegrating the coating solution into droplets; transporting the droplets to the medical implant so that the majority of the droplets have a tangential velocity component in relation to the surface of the medical implant; and depositing the droplets with an asymmetric splat morphology on the medical implant to form a coating.

2. The method according to claim 1 , further comprising the step of changing the tilt angle between the spray axis and the surface of the medical implant during the coating process in order to vary the morphology of the coating layer.

3. The method according to claim 1 , wherein the medical implant is a stent.

4. A method to apply a coating to a medical device using means to disintegrate a coating composition into droplets and means to generate a vortical gas flow field having a swirl intensity between 0.01 and 2.5 to transport the droplets to the medical implant, comprising the steps of: disintegrating the coating composition into droplets; transporting the droplets in said gas flow field to the medical device so that the majority of the droplets have a tangential velocity component in relation to the surface of the medical device; and depositing the droplets on the medical device.

5. The method according to claim 4, wherein the coating composition is disintegrated by the vortical gas flow field.

6. The method according to claim 4, wherein the means to generate the vortical gas flow field comprise a conduit with at least a first and a second gas inlet and at least one gas inlet is used to induce swirl motion in the gas flow.

7. The method according to claim 4, wherein the swirl intensity can be changed by adjusting the ratio between the axial gas flux of swirl momentum and the axial gas flux of axial momentum.

8. The method according to claim 4, further comprising the step of changing the swirl intensity during the coating run in order to vary the morphology of the coating along the surface of the substrate.

9. The method according to claim 4, wherein the medical device is a stent.

10. The method according to claim 4, wherein the coating composition comprises a therapeutic agent.

11. The method according to claim 4, wherein the coating comprises pores.

12. A method to apply a coating to a medical device using means having at least one exit aperture to generate droplets from a coating composition and suction means to generate a gas flow field having at least one entrance aperture, wherein the medical device is positioned between said exit aperture and said entrance aperture, comprising the steps of: disintegrating the coating composition into droplets; generating a gas flow field to direct the droplets to the substrate so that the majority of the droplets comprise a tangential velocity component in relation to the surface of the medical device; and depositing the droplets on the medical device with an impact angle other than 90 degrees.

13. The method according to claim 12, wherein the droplets are formed through vibration.

14. The method according to claim 12, wherein the droplets are formed through electrostatic energy.

15. The method according to claim 12, wherein the medical device is a stent.

16. The method according to claim 12, wherein the entrance aperture is tilted in relation to the spray axis.

17. The method according to claim 15, wherein the tilt angle of the entrance aperture can be changed during the application of the coating to vary the morphology of the coating.

18. The method according to claim 12, wherein the entrance aperture of the suction means is positioned at an offset distance from the spray axis of the droplet generating means.

19. The method according to claim 18, wherein the position of the entrance aperture can be changed during the application of the coating to vary the morphology of the coating.