Drug-eluting coatings applied to medical devices by spraying and drying to remove solvent

Abstract

A coating device for coating a medical device with a drug-eluting material uses an in-process drying station between coats to improve a drug release profile. The drying station includes a heat nozzle configured for applying a uniform drying gas. A coating process using the dryer includes a closed-loop control for the gas between drying steps and an improved nozzle for producing more consistent spray patterns.

Claims

1. A method of drying a stent having a longitudinal axis, comprising: using a dryer having an inlet conduit for supplying an input gas and a nozzle exit for producing a heated, drying gas, the nozzle exit having apertures; and placing the stent between a reflector and the nozzle exit, wherein the reflector is arranged to cause an increase in gas pressure near the stent by directing gas towards the stent, thereby reducing heat loss in the vicinity of the stent; wherein the dryer is adapted for producing a substantially uniform drying air mass over the stent length.

2. The method of claim 1, wherein the stent is held by a mandrel having a longitudinal axis, and wherein the longitudinal axis is between the reflector and the nozzle exit.

3. The method of claim 2, wherein the apertures are arranged to extend parallel to the longitudinal axis.

4. The method of claim 1, wherein the reflector has a curved surface comprising one of a parabolic or semi-circular surface when the reflector is viewed in a plane, and wherein the longitudinal axis extends perpendicular to the plane.

5. The method of claim 1, wherein the reflector has a curved surface when the reflector is viewed in a plane, and wherein the longitudinal axis extends perpendicular to the plane.

6. The method of claim 1, wherein a gas expander is attached to the nozzle exit.

7. The method of claim 6, wherein the stent has a diameter and the stent is placed within about 25% of a height of the expander, or about a length of the stent diameter within a mouth of the expander.

8. A method of drying a stent having a longitudinal axis, comprising: using a dryer having an inlet conduit for supplying an input gas and a nozzle exit for producing a drying gas, the nozzle exit having an array of apertures, and a gas expander attached to the nozzle exit; placing the stent fully within or partially within the gas expander; and drying the stent; wherein the dryer is adapted for producing a substantially uniform drying air mass over the stent length.

9. The method of claim 8, wherein the stent is placed within a mouth of the expander.

10. The method of claim 9, wherein the gas expander has a mouth and a height measured from the nozzle exit to the mouth, and the stent is placed within the expander and about 25% of the height from the mouth, or a distance equal to about a diameter of the stent from the mouth.

11. The method of claim 8, wherein the gas expander has a pair of curved surfaces.

12. The method of claim 11, wherein the stent has a longitudinal axis and the pair of curved surfaces is viewed in a plane perpendicular to the longitudinal axis.

13. The method of claim 12, wherein the gas expander is conical or parabolic when viewed in the plane.

14. The method of claim 8, wherein the gas expander is made from a heat insulating material.

15. The method of claim 8, wherein the array of apertures are a linear array of apertures that extend parallel to the longitudinal axis.

16. The method of claim 8, wherein the expander has a height measured from the nozzle exit to the mouth, and a width, and the expander height is equal to four times a diameter of the stent, and/or the expander has a height to width ratio of 1:1.

17. The system of claim 8, wherein the stent has a longitudinal axis and the array of apertures are a linear array of apertures that extend parallel to the longitudinal axis.

18. A method of drying a stent having a longitudinal axis, comprising: using a dryer having an inlet conduit for supplying an input gas and a nozzle exit for producing a drying gas, the nozzle exit having an array of apertures, and a conical or parabolic skirt attached to the nozzle exit; placing the stent fully within or partially within the skirt; and drying the stent; wherein the dryer is adapted for producing a substantially uniform drying air mass over the stent length.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a perspective view of a dryer according to one aspect of the disclosure. The dryer is supplied a gas through a conduit of a heater assembly.

(2) FIG. 2A is a top view of the dryer of FIG. 1.

(3) FIG. 2B is a side cross-sectional view of the dryer of FIG. 1 taken at section AB-2B in FIG. 2A. As depicted here, a gas stream v.sub. enters the dryer at an entrance. The gas velocity is abruptly decreased (v.sub.1) as it encounters a wall, at which point it is forced upwardly. The increased pressure causes the gas to expand into an upper chamber of a plenum (v.sub.2). Here the high pressure area causes the gas to make another right hand turn and exit at higher velocity through a diffuser. The gas in (V1) enters a second chamber. This chamber slows the gas down again, then causes it to accelerate upwardly until it exits from a nozzle exit (v.sub.3). The gas exiting the nozzle is uniform in temperature and velocity and extends over a linear length (gas curtain) for drying a stent (s) disposed over the nozzle.

(4) FIG. 3A is a forwardly looking, exploded assembly view in perspective showing component parts of the dryer of FIG. 1.

(5) FIG. 3B is a close-up view of a portion of a nozzle component of the dryer near the nozzle exit taken from section 3B in FIG. 3A.

(6) FIG. 4 is a rearwardly looking, exploded assembly view in perspective showing component parts of the dryer of FIG. 1.

(7) FIG. 4A is a front view of a plenum portion of the dryer of FIG. 1

(8) FIG. 4B is a frontal view of portion of the dryer of FIG. 1. The diffuser is mated with the plenum to form a T-shaped gas conditioning chamber. Flow apertures are formed on the diffuser.

(9) FIG. 5 is a schematic view of a dryer and reflector drying the stent S. Illustrated in this schematic are streamlines of heated gas exiting the nozzle of the dryer of FIG. 1 and reflecting or being constrained to form an area of high pressure in the vicinity of the stent.

(10) FIG. 6 is a schematic view of a dryer and gas expander drying the stent S. Illustrated in this schematic are streamlines of heated gas being expanded as the gas travels through the gas expander. The gas expander acts as a partition that segregates the hot gas as it expands from the surrounding cool gas and improves the uniformity of the gas properties in the vicinity of the stent.

(11) FIG. 7A is a schematic view of gas flow controller for the dryer of FIG. 1. The controller is configured for producing a constant temperature gas flow into the dryer for variable and steady state flow rates.

(12) FIG. 7B is a perspective view of a stent spraying and drying assembly incorporating aspects of the disclosure.

(13) FIGS. 8A-8C are perspective, side and a cross-sectional view of a spray nozzle according to another aspect of the disclosure. The cross-sectional view is taken at section 8B-8B in FIG. 8C.

(14) FIG. 9 is a prior art spray nozzle. The spray nozzle of FIGS. 8A-8C is an improvement over the spray nozzle of this figure. The spray nozzle of FIG. 8 produces a more consistent atomized stream of a drug-polymer-solvent, and has less clogging than the prior art nozzle of FIG. 9.

DETAILED DESCRIPTION OF EMBODIMENTS

(15) According to a preferred implementation of the invention, a sprayer and heat nozzle is used to form a drug-eluting coat on a surface of a stent. A stent is an intravascular prosthesis that is delivered and implanted within a patient's vasculature or other bodily cavities and lumens by a balloon catheter for balloon expandable stents and by a catheter with an outer stent restraining sheath for self expanding stents. The structure of a stent is typically composed of scaffolding, substrate, or base material that includes a pattern or network of interconnecting structural elements often referred to in the art as struts or bar arms. A stent typically has a plurality of cylindrical elements having a radial stiffness and struts connecting the cylindrical elements. Lengthwise the stent is supported mostly by only the flexural rigidity of slender-beam-like linking elements, which give the stent longitudinal flexibility. Examples of the structure and surface topology of medical devices such as a stent and catheter are disclosed by U.S. Pat. Nos. 4,733,665, 4,800,882, 4,886,062, 5,514,154, 5,569,295, and 5,507,768.

(16) As discussed earlier, one aspect of the stent coating process that has been simplified, or improved, as a result of the dryer according to the disclosure, is the ability to predict more consistently the rate of solvent removal and variation over the length of the stent of that rate. Increasing the predictability of a solvent's presence in the applied coating, or remaining when determining a final weight can greatly increase the ability and/or efficiency in which a predictable release rate for a drug can be provided in a medical device, in the form of an applied coating.

(17) Moreover, as the design or desired loading of polymer-drug on the stent is determined from the measured weight, it will be readily appreciated that there needs to be an accurate, reliable and repeatable process for being able to determine the amount and distribution of solvent remaining over the length of the stent. This is especially true when less volatile solvents are used, e.g., DMAc as opposed to the more volatile solvent Acetone. Since it is expected that a greater percentage of solvent will remain after drying for solvents having higher boiling points, the coating is more susceptible to variations in a solvent's presence over the stent surface and/or across the coating thickness.

(18) The disclosure provides examples of spraying/drying components suited for addressing the previously discussed drawbacks and limitations in the art pertaining to a drug-eluting coating applied via a drug-polymer dissolved in a solvent.

(19) Dryer Assembly

(20) FIG. 1 shows a perspective view of a dryer 1 according to one aspect of the disclosure. The dryer 1 may be included as a component used in a stent coating process. Such a stent coating station implementing a process may include a sprayer, the dryer 1 and actuators for selectively placing the sprayer and dryer over the stent between spraying and drying steps, respectively. Examples of a stent coating system that may adopt principles of the disclosure are described in U.S. patent application Ser. Nos. 12/497,133; 12/027,947 and 11/764,006. In these examples, the dryer(s) and spray nozzle(s) described therein may use a dryer and spray nozzle according to the disclosure, as will be understood.

(21) A coating process may be preprogrammed, or programmed on the fly to adjust parameters such as number of coats, or passes with the sprayer between drying steps, number of cycles of spraying and drying, etc. These and related parameters may be governed by the polymer-drug or solvent used, type of stent or medical device being coated, e.g., surface geometry. In particular embodiments the protocol for coating a stent may be governed by a predetermined number of coating cycles, i.e., spraying then drying, based on an analytically determined final coating weight, or by intermittent weighing of the stent to determine the number of cycles needed to arrive at the target coating weight.

(22) The stent may be held in a mandrel and rotated as the sprayer applies a drug-polymer dissolved in a solvent, e.g., DMAc, to the surface of the stent. After one, two or more passes over the body of the stent with the sprayer, the dryer 1 is moved into position over the stent. The nozzle exit 3 is placed beneath the stent (or the stent moved into a drying position above the nozzle exit 3) at this stage of the process, so that the stent length extends lengthwise over the nozzle 3, i.e., parallel to the direction measuring the length L in FIG. 1. Once in position, a mass of heated gas exits from the nozzle exit 3 to accelerate the evaporation, or boiling-off of solvent from the coated stent surface. In a preferred embodiment, this sprayer-dryer coating process is repeated until a final coating weight of drug-polymer and remaining solvent is measured. During each drying stage of preferred embodiments, the gas produces a uniform heat transfer across the surface of 100 mm, 150 mm, and 200 mm stent. After a final coating weight has been reached, the stent may be placed in an oven for an extended period to remove additional solvent.

(23) As illustrated, the dryer's exit nozzle 3 is configured to produce the mass of heated gas (represented by the array of vectors M.sub.g extending upward from the nozzle exit 3 in FIG. 1) over a linear length L, which may correspond to the length of the coated stent positioned for drying. FIG. 2B, which is a partial side cross-sectional view of dryer 1 taken at section 2B-2B in FIG. 2A, shows the stent S in position opposite the nozzle exit 3. The drying gas, e.g., heated nitrogen, is supplied through a gas supply 2b connected to a heater assembly 2. The heater assembly 2 includes a tubular conduit with heating coils (not shown) exposed to the gas stream as it travels towards the plenum 10 (as represented by vector V in FIG. 2B). The coils are connected to a power source via a power connection 2a.

(24) The gas traveling over the length of the heater assembly 2 is heated to a desired temperature and the gas pressure is known. Thus, gas entering the plenum 10 has a predetermined velocity and temperature (a thermocouple may be placed near the entrance to measure gas temperature). The gas may be treated as an incompressible fluid between the entrance 12 of the dryer 1 and exit 3. The velocity of gas passing through any cross-section, therefore, may be considered inversely proportional to the size of the cross-section assuming no significant heat loss through the walls of the dryer (conservation of mass). In a preferred embodiment, the plenum, diffuser and nozzle portions of the dryer are made of PEEK plastic to minimize heat flow between the interior of the dryer and exterior environment. PEEK may be used for maximum temperatures of up to 200 degrees Celsius.

(25) FIG. 4 is a rearwardly-looking exploded view of the dryer 1 showing its component parts, i.e., a plenum 10, a diffuser plate 50 and a nozzle 30. FIG. 3A is a forwardly-looking exploded view of the dryer 1 showing these same components. Mounting blocks 11a, 11b are used to mount the dryer 1 to a support of a sprayer-dryer assembly, e.g., the spray-dryer assembly 350 of FIG. 7B, and a coupling or threaded sleeve 15 connects the heater assembly 2 to the dryer 1 entrance 12.

(26) The diffuser 50, disposed, between the plenum 10 and nozzle 30, acts a divider between two distinct and functionally different chambers for conditioning the incoming gas. These are the plenum volume, space or chamber 14 and nozzle volume, space, or chamber 34 for flow conditioning. The assembly of the components may be described as the plenum 10 and diffuser 50 portions together forming a plenum chamber 14 and the nozzle 30 and diffuser 50 portions together forming a nozzle chamber 34 for dryer 1. The diffuser 50 includes apertures 52 that may be of the same diameter and evenly spaced over the length (seven are shown in FIG. 4) for passage of gas from the plenum chamber 14 to the nozzle chamber 34 after the gas has been first conditioned (as describe below) by the plenum chamber 14. The gas mass M.sub.g is then conditioned for a second time in the nozzle chamber 34 before it exits the nozzle exit 3 from the nozzle chamber 34.

(27) Plenum chamber 14 features are described with reference to FIGS. 2B, 4, 4A and 4B. The plenum chamber 14 is generally T-shaped, formed by a cavity 16 of the plenum 10 and the rear face 56 of the diffuser plate 50. This chamber is sealed, with the exception of the upstream cylindrical entrance passage 12 (incoming gas from heater assembly 12) and the downstream array of apertures 52 that provide a fluid passage between the plenum chamber 14 and the nozzle chamber 34.

(28) An upper portion 16b formed by the section extending from left to right in FIG. 4A and preferably having the length L (see also FIG. 1) mates with the diffuser plate 56 portion 56b having the array of apertures 52. A lower portion 16a formed by the section containing the entrance 12 mates with the diffuser portion 56a that is devoid of an aperture or opening to the nozzle 34 chamber. Thus, when gas enters the plenum chamber 14 lower portion from the cylindrical opening 12, it is immediately decelerated and gas pressure increases. This forces gas upwards into the expanded space of the plenum chamber 14. Gas accumulated under this pressure in the upper portion 16b then exits from the plenum chamber 14 and enters the nozzle chamber 34 via the array of apertures 52, which are arranged essentially over the same length L as the exit nozzle 3, but with a larger opening (or total flux area) than the exits 40 at the nozzle 3.

(29) In one embodiment the total flux area for gas flow through the apertures is about 0.344 in.sup.2, as compared to 0.0864 in.sup.2 at the nozzle exit 3. The total flux area at the inlet is about 0.196 in.sup.2. The ratio of the inlet to diffuser total flux area may be about 1:1.75, about 1:2 or between about 1.5:1 and 2:1. The ratio of the diffuser to the exit total flux area may be about 4:1. In one embodiment, the ratio of the exit total flux area (E) to the diffuser total flux area (D) to the inlet total flux area (I), i.e., the quantity E:D:I, is between about 1:4:2 to 1:4:2.5. In other embodiments, the diffuser total flux area is greater than the inlet total flux area and the inlet total flux area is greater than the nozzle exit channel total flux area.

(30) Nozzle chamber 34 features are described with reference to FIGS. 2B, 3, 3A and 4. As can be best appreciated in FIGS. 3 and 3A, the chamber 34 is formed by mating the front face of the diffuser 50 with the nozzle 30 so that surfaces 35 and 45 of the nozzle 30 abut the face of the diffuser 50 (FIG. 2B). The diffuser 30 has formed therein a cavity 36 bounded by surfaces 35 and 45. At the upper end (near the nozzle exit 3) a linear array of nozzle exit channels 40 form rectangular notches 42 over the length L of the cavity 36. When the cavity 36 is mated with the flat, opposing face of the diffuser 50, the channels 40 provide an array of rectangular passageways that produce a flow pattern having reduced turbulence, and more uniform gas flow from the nozzle chamber 34 out through the nozzle exit 3 along the length L.

(31) Referring to FIGS. 2B, 3 and 3A, at the lower end of the chamber 34 there is a relatively wide base portion, followed by a tapered portion. At the upper end of the tapered portion the chamber has its narrowest point, which is where lower, tapered ends 43 are formed to reduce turbulence and therefore noise at the nozzle exit 3 (as described in greater detail below). The chamber 34 is therefore configured as a converging channel extending upwards in FIG. 2B, and at a right angle to the average gas flow direction through the apertures 52. That is, the gas flow makes a 90 degree turn upwards when it reaches the nozzle chamber 34. Pressure builds in the lower portion of the chamber 34, as a result, then gradually reduces (as the section narrows) until the gas exits from the nozzle exit 3 where there is a sharp decrease in pressure to atmospheric pressure.

(32) Referring to FIG. 3B, at the lower end of each of the channels 45 there are sloped surfaces that form a converging point. Placed side by side the channels 40 having the tapered end 43 form a converging channel for gas flow traveling up from the lower portion of the chamber 34. It was found that by forming the tapered ends 43, or converging channels leading to the exit 3, the flow tended to be more laminar at the exit. Additionally, vibrations presumably caused by oscillating gas flow emanating from the exits 40 was significantly reduced when the ends of channels 40 were tapered. As a result, there was a significant reduction in vibro-acoustic noise caused by the exiting gas mass M.sub.g. This reduced the noise that operators of a spray station would encounter during operation.

(33) In a preferred embodiment, the ratio of output length (L), i.e., length of array of channels openings 40 at exit 3, to the input diameter at the inlet 12 (D), to the height of the internal space from the plenum chamber 14 lower surface to exit 3 (H), to the depth from the leftmost wall of the nozzle chamber 34 in FIG. 2B to the rightmost wall of the plenum chamber 14 (2R), or the ratio L:D:H:2R is about 1:(1/10):(1/3):(1/8). Thus, for a length (L) of 100 mm, the depth of the gas conditioning chambers is about 10 mm, the height of the gas conditioning chambers is about 33 mm and the diameter at the inlet is about 10 mm.

(34) According to one embodiment of the dryer 1, which is configured for drying a stent having a length of 200 mm, the length of the nozzle exit is preferably about 250 mm to ensure that the ends of the stent are not subject to variations in the flow or influence by ambient air at the ends of the nozzle, so called end effects. As explained in detail above, these values were obtained from results indicating the lengths of the nozzle exit relative to the stent length that would not produce an inconsistent or irregular rate of removal of solvent near the edges. The verification of this minimal length was determined only through testing (if sensitive nature of remaining solvent's effect on release rate were not a concern, of course one would prefer having the nozzle gas exit being more closer to stent length to conserve gas resources and increase drying efficiency). In some embodiments the nozzle length may be about 25% wider than the longest stent length suited for the dryer, so that end effects are negligible. In other embodiments, the total length of the nozzle may be about 1.5 times the total length of the longest stent suitable for the dryer, so that end effects, i.e., effect on solvent irregularity and therefore release rate, are negligible.

(35) According to a preferred embodiment, a dryer flow setting is 100 standard liters/minute gas flow, and a temperature setting of approximately 100 to 120 degrees C.

(36) Closed-Loop Controller

(37) A gas flow rate through the heater assembly 2 in FIG. 1 may be monitored/controlled by a commercially available mass flow regulator (not shown). For example, such a mass flow regulator may be used to operate an adjustable valve coupling the gas supply line 2b to a gas source to produce the desired flow rate. One example of a suitable mass flow regulator is the Aalborg GFCS series programmable mass flow regulator. A use of a mass flow regulator and related control system suitable for use with aspects of the disclosure is described in U.S. application Ser. No. 12/540,302.

(38) During a coating process, the dryer is not in use when the stent is being coated. If the dryer is shut down or the flow rate reduced the temperature of the gas at the entrance to the plenum 10 of the dryer 1 will decrease. If the stent is moved into position above the nozzle exit 3 for drying and the valve opened to increase the flow rate, there will be a period of transient flow. It is desirable to avoid a period of solvent removal by transient gas flow, since the rate or amount of solvent removal by transient flow can be difficult to predict. It is preferred, therefore, that the stent is dried only during steady state flow conditions.

(39) If gas flow at the dryer is instead maintained at a constant rate, then the temperature may be maintained. However, this wastes gas resources. It would be desirable if the gas flow rate could be reduced when the dryer is not in use while holding the gas temperature at a constant value.

(40) To meet this need, a closed loop control is preferably implemented with a stent dryer system according to the disclosure, so that the gas temperature may be maintained at variable flow rates. Referring to FIG. 7A, a schematic of this closed-loop control is illustrated. A controller 300 continuously receives input temperatures at the entrance of the plenum from a thermocouple 302 and the gas flow rate upstream of the plenum entrance from a flow sensor 304. The controller 300 may be programmed to reduce the gas flow rate when the dryer is not in use, and increase the gas flow rate when the stent is ready to be moved into position above the nozzle exit 3.

(41) As the flow rate is adjusted by opening/closing the adjustable valve 308, the controller senses a change in temperature from input received at the thermocouple 302, at which point it will increase/decrease the power delivered to the heating coils by affecting control 306 for power so that the temperature remains constant, regardless of the actual flow rate. Thus, according to this aspect of the disclosure, a dryer system may be operated at variable flow rates during a coating process while maintaining a substantially steady state gas flow during the drying stage, or a minimal period of transient flow conditions until a steady state condition is reached. This improves/maintains the predictability of solvent removal during drying, minimizes down time and allows gas resources to be conserved. The coated stent is almost immediately subject to the drying step and dried in a manner that allows the improved prediction of solvent removal. As discussed earlier, this is a critical step in the process of producing a predictable release rate for a drug-eluting stent and accurate assessment of whether the desired drug-polymer coating weight has been reached.

(42) A closed loop controller in accordance with the foregoing may be incorporated into a spray-dryer assembly of the type described in U.S. application Ser. No. 12/540,302.FIG. 7B is a reproduction of FIG. 3A of this application. In this assembly 350, a pair of stents on mandrels (not shown) are supported from right-side spindle assemblies 360 (spindles 362), which are disposed on respective left and right sides of a spray isolator enclosure 352. According to this configuration, a pair of supported stents on one side of the spray isolator enclosure 352 are dried while a pair of stents supported on the opposite side of the spray chamber 352 are sprayed. The spindle assemblies 360 rotate the stents during drying and spraying. A spray nozzle 400 is shown disposed within the chamber. When moved into, or out of the spray isolator enclosure 352 the stents on mandrels are passed through openings 364. A left and right pair of dryer nozzles (each being the nozzle 30 of dryer 1) are shown disposed between the respective left-side and right-side spindle assemblies 360 in FIG. 7B and the spray isolator enclosure 352 (only one of these left and right pairs of nozzles 30, respectively, is visible in this view). The stents are dried in area 363.

(43) One of a pair of left and right stents may be sprayed and dried using the controller 300 assembly 350 according to the following steps. First, the stents are placed within the spray isolator enclosure 352 for spraying. During, or prior to the spraying, the gas flow to the nozzles 30 is set at an idle setting with the controller increasing the power to the heating coils as necessary (based on input received from the thermocouple 302) until the temperature of the gas flow reaches a steady state condition. A transducer 354, mounted on a spindle assembly 360, may also be used to measure the exit temperature above the nozzle.

(44) After, or just prior to completion of an application of coating material on the stents using the nozzle 400, the controller 300 increases the gas flow temperature to the drying gas flow rate. While the gas flow is being increased, the controller 300 monitors the temperature at the plenum entrance 12 by input received from the thermocouple 302 and the power decreased to the heating coils as necessary to maintain the temperature of the exiting gas flow. Once the gas flow has reached the operating flow rate and temperature, the stents are moved into the drying area 363. The stents are rotated by a rotation mechanism built into the spindle assembly 360. After drying is complete the gas flow is again returned to the idle position and the power to the heating coils increased as necessary to maintain the same gas flow temperature (based on input received from the thermocouple 302). The process repeats until the desired coating weight is obtained.

(45) Reflector and Expander Embodiments

(46) According to another aspect of the disclosure a dryer includes structure external to the dryer nozzle exit 3 to control or effect the interaction between ambient air and gas exiting the dryer and surrounding the stent. As will be appreciated, when gas exits the nozzle at high velocities there is a corresponding drop in pressure, which causes the ambient air to be drawn in towards the nozzle exit and stent surface and mix with the hot gas. As a result, the cooler ambient air draws heat away from the hot gas exiting the nozzle and reduces the efficiency of the hot gas to remove solvent.

(47) In one embodiment, a dryer is configured in combination with a reflector to redirect or focus gas passing by the stent S back towards the stent to increase the efficiency of the hot gas to evaporate or boil off solvent from the stent surface. FIG. 5 illustrates the stent S disposed between a curved reflector 120, e.g., parabolic or semicircular, and the dryer 1, and the circulation of hot gas around the stent and reflected by the reflector surface 122. In the region between the reflector 120 and the stent S the gas pressure is increased. As a result, the cooler ambient air mixes less with the hot gas and draws less heat away from the gas passing by the stent.

(48) In another embodiment, a gas expander 140 is fitted over the nozzle exit to shield or insulate the hot gas exiting from the dryer from the cooler ambient air, as depicted in FIG. 6. As the gas exits the nozzle it expands as it travels through the expansion space formed by expander 140. This increases the gas pressure surrounding the stent, thereby causing less heat loss before the gas reaches the stent surface. The higher pressure also serves to maintain the uniformity of gas in the vicinity of the stent. This is depicted in FIG. 6 by the turbulent mixture of ambient air and hot gas that forms in areas away from the stent surface. The stent may be placed near, partially within or fully within the expander 140.

(49) In some embodiments the gas expander may be sized based on the diameter of the stent, as depicted in FIG. 6. The stent's diameter D is shown. The width of the mouth, and height of the expander section are both 4 D, or about four times the stent diameter. And the stent is sunken into the expansion chamber by about 1 D, as illustrated. In other embodiments the mouth may be less than 4 D while the height is the same. In one embodiment, the mouth is 2 D while the height is 4 D. It is believed that the more narrow mouth according to this embodiment will produce a more uniform gas temperature and velocity about the stent, while making the placement within the expander during a high volume coating/drying process easy to implement, or without other drawbacks resulting from a more narrow mouth, as will be appreciated. preferably, however, the mouth diameter is 4 D.

(50) In some embodiments the stent may be placed closer, or further from the nozzle exit 3. If the stent is placed too close to the nozzle exit 3, the distance between the leading edge of the stent and exit may create an uneven flow condition, which can cause the stent to be jostled about. In other embodiments the stent may be moved further than 3 D from the nozzle but within the mouth. A stent placed outside of the mouth may not benefit as much from the environment provided by the gas expander. In those cases the ambient air may interfere with the velocity and temperature near the stent surface, thereby producing more unpredictable results or loss of drying efficiency. It is believed that an optimal efficiency and uniformity may be achieved when the stent is placed 1 D within the mouth, 3 D from the nozzle, and the gas expander mouth and height are respectively, 4 D and 4 D. In some embodiments the stent is placed at 75% of the mouth distance from the nozzle and the ratio of width to height is 1:1. It was found that with this condition, uniformity of solvent removal was maintained, or indeed improved and efficiency of solvent removal improved. Further, as mentioned earlier, in some embodiments the optimal distance may be found from the solution to the optimization constrained by three variables: (1) expander design, (2) heat transfer associated with gas and surrounding environment and (3) the type of stent support used.

(51) Spray Nozzle

(52) According to another aspect of the disclosure a spray nozzle is manufactured to reduce clogging and improve consistency of a drug-polymer dissolved in a solvent.

(53) Referring to FIG. 9, a prior art spray nozzle 200 is shown. The nozzle 200 is an atomizing spray nozzle that may be used to produce a conical spray pattern of an atomized solution of a fluid. The nozzle may use a constant airflow with pulsed delivery to produce the atomized spray pattern. A prior art spray nozzle suitable for this use is the Sonicair nozzle available from the IVEK Corporation, 10 Fairbanks Rd. North Springfield, Vt. 05150 USA.

(54) The nozzle 200 includes a housing 201 having a first bore formed to receive a cannulae 220, which carries the fluid to the nozzle tip 203, and a third and fourth bore 210 and 214 which provides a conduit for pressurized gas used to atomize the fluid at the tip 203. A threading is provided at the opposite end for connecting a liquid supply line 220A and gas supply line 210A.

(55) At the exit 203 a nozzle cap 213 having a centrally located orifice, sized according to the desired droplet size in the spray pattern, is placed over the exit hole 202 of the cannulae 220, which is in fluid communication with a chamber 215 in fluid communication with pressurized gas conduits 210, 214.

(56) It was discovered that drug-polymer coatings applied using the nozzle 200 produced unacceptable variations in spray patterns and frequent clogging. Certain modifications (as described below) were made to the nozzle in the hopes that these problems could be eliminated.

(57) Surprisingly and unexpectedly, it was found that a much improved spray pattern and less frequent clogging occurred when these modifications were implemented.

(58) When it was discovered that the coating process could be significantly improved overall by improving upon the nozzle, attempts were made to improve on the existing prior art nozzle by polishing interior and exterior surfaces proximal the nozzle orifice. It was discovered during tests using a particular polymer-drug-solvent solution, e.g., 93% solvent and 7% drug-polymer, and desired conical spray pattern that the exiting prior art nozzle contained several shortcomings. In short, for the particular application of a drug-polymer coating according to one aspect of the invention it was discovered that the commercial nozzle, an example of which is provided here, although designed to produce precise and consistent spray patterns for applying a drug-eluting coating to medical devices and, in particular, stents, fell well short of the requirements for a drug-eluting coating having the required tolerance in the coating weight and distribution needed to achieve the objects of the disclosure, as previously discussed.

(59) Two aspects of the nozzle that were found to produce inconsistent results were manufacture by an EDM process and nozzle-to-nozzle variations due to tolerances for parts during manufacture being too large. Polishing inner and outer areas proximal the nozzle orifice, for example, was not enough by itself to solve the problems. Nor was switching to a different design of sprayer. For example, an ultrasonic-type nozzle was tested. This alternative did not improve results as non-uniform and inconsistent coatings were found on a stent sprayed using an ultrasonic-type nozzle.

(60) FIGS. 8A illustrates a perspective view of an improved spray nozzle 400 according to the disclosure. FIG. 8C shows a side view of this nozzle and FIG. 8B shows a cross-sectional view of the nozzle 400 taken at section 8B-8B of FIG. 8C. The nozzle has a housing 401 which has a modified bore for receiving a modified cannulae 420, bores 410, 412 for passage of pressurized air and an exit end 403. A nozzle cap 413 is located at the nozzle end 403. The atomized drug-polymer-solvent solution exits from a modified orifice 401a.

(61) Some of the important features of the nozzle of FIGS. 8 that differ from the prior art nozzle of FIG. 9 are the finishing on the fluid surfaces, material, smoothness and consistency of the orifice hole and tight tolerances enforced in the nozzle passages.

(62) The first improvement was in the use of different material. The housing 401 is made from 17-4 PH 900 heat treated steel whereas the cannulae 420 is made from 316 stainless steel. The nozzle 200, in contrast, is made from 316 stainless steel throughout. By using different materials in nozzle 400 having a different hardness, there is a tighter control of the press fit between the cannulae 420 and housing 401. Moreover, galling between the housing 401 and cannulae 420 is eliminated due to the different material, i.e., the 316 steel being a softer metal than the 17-4 PH 900 heat treated steel.

(63) The second improvement was in the formation of the orifice of the end cap. The nozzle 200 end cap 213 is formed by a standard edge break on the inside and outside edges of the tapered orifice. This produced machining marks and variations around the orifice contributing to an inconsistent spray pattern (a result of an EDM manufacturing process). The end cap 413 for the nozzle 400 was instead made with more precise tolerance control. Additionally, surfaces on the inside and outside of the orifice were polished to produce more uniform surfaces for passage of the atomized fluid through the orifice (the end of the cannulae facing the orifice was also polished). These improvements in the nozzle cap 413 reduced instances of clogging, and produced a more uniform spray pattern as compared to the nozzle 200 end cap 213.

(64) A third improvement was made in the cannulae. First, the cannulae was made with a stepped outer diameter for precise placement against a ledge 420A formed in the receiving bore of the housing. Mating with a stepped diameter bore also prevented the cannulae 420 from being pushed into the end cap 413 when the fluid supply fitting is secured at the connection 420A. The cannulae 220, by contrast, is formed as a constant diameter cylinder and received in a corresponding constant diameter bore. This assembly makes placement of the cannulae 220 within the bore less precise and the fit less snug.

(65) Second, the cannulae 420 bore is made larger and steps down to a smaller diameter bore, which reduces the pressure drop along the length of the cannulae 420. The cannulae 220 of the nozzle 200 has instead a constant bore. By reducing the pressure drop there is a more consistent supply of fluid at the desired pressure, which contributes to a more consistent spray pattern.

(66) A fourth improvement in nozzle performance relates to a method of reducing instances of clogging, particular between spraying intervals, i.e., when the stent is moved to the dryer. A buildup prevention method for a nozzle includes a secondary nozzle having its nozzle orientated towards, and at an angle of about 20-40 degrees relative to the nozzle cap 413 lower face. This nozzle delivers a steady stream of gas, e.g., Nitrogen gas, towards the orifice 401a between each spraying step. By applying this steady stream of gas a buildup of drug-polymer solution is forcably blown off the orifice of the spray nozzle as the nozzle rests between spray cycles. Simultaneous with this applied gas is a sufficiently high pressure being maintained through the atomizing gas pressure source. This should prevent any buildup of drug-polymer solution from being blown into the bore of the cannulae 422 due to the secondary nozzle drying gas. In one embodiment, the 20-40 orientated drying gas was delivered at an exit pressure of 5-20 psi for about 1-3 seconds. The balancing pressure of the atomizing gas may be the same as the operating pressure, e.g., the recommended operating pressure for the Sonicair nozzle. According to this aspect of the disclosure, a stent drying and spraying process includes a spray nozzle drying step intermittent to spraying steps.

(67) Although the above embodiments have been described in connection with a stent, it is to be understood that the present invention can be applied to devices other than stents. Medical devices to which this invention may be adapted for use includes balloon expandable stents, self-expanding stents, grafts, stent-grafts, balloons, and catheters.

(68) While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.