Vapor annealing treatments to improve coating durability and drug transfer

Abstract

Medical devices and methods for making, using, and treating medical devices are disclosed herein. An example method for treating a medical device is disclosed herein. The method may include disposing an annealing fluid in a closed chamber, allowing the annealing fluid to achieve a liquid-gas equilibrium inside the chamber, and disposing a drug-coated medical device inside the closed chamber.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 346,140, ​​filed on May 26, 2022, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present disclosure relates to medical devices and methods of manufacturing medical devices. More specifically, the present disclosure relates to coated medical devices. Background Art

[0003] A wide variety of intracorporeal medical devices have been developed for medical use, such as intravascular use. Some of these devices include guidewires, catheters, and the like. These devices can be manufactured by a variety of different manufacturing methods and can be used in a variety of different ways. Of the known medical devices and methods, each has its own particular advantages and disadvantages. There continues to be a need for alternative medical devices and alternative methods of manufacturing and using medical devices. Summary of the invention

[0004] The present disclosure provides alternatives for the design, materials, manufacturing methods and uses of medical devices. A method for treating a medical device is disclosed. The method includes: placing an annealing fluid in a closed chamber; allowing the annealing fluid to reach liquid-gas equilibrium in the chamber; and placing a medical device coated with a drug in the closed chamber.

[0005] Alternatively or additionally to any of the above embodiments, the annealing fluid comprises isopropyl alcohol.

[0006] As an alternative or addition to any of the above embodiments, the closed container has a substrate, wherein placing the annealing fluid in the closed chamber includes coating the substrate with the annealing fluid.

[0007] Alternatively or additionally to any of the above embodiments, coating the substrate with the annealing fluid includes coating the substrate to form a 1-10 mm thick annealing fluid layer.

[0008] As an alternative or addition to any of the above embodiments, allowing the annealing fluid to reach liquid-vapor equilibrium in the chamber includes partially evaporating the annealing fluid.

[0009] Alternatively or additionally to any of the above embodiments, allowing the annealing fluid to reach liquid-vapor equilibrium in the chamber includes partially evaporating the annealing fluid for at least two hours.

[0010] As an alternative or addition to any of the above embodiments, placing the medicated medical device in the closed chamber includes placing the medicated medical device in the closed chamber for at least two hours.

[0011] As an alternative or addition to any of the above embodiments, the drug-coated medical device includes a drug coating, wherein placing the drug-coated medical device in the closed chamber includes vapor annealing the drug coating.

[0012] As an alternative or in addition to any of the above embodiments, the drug coating comprises everolimus.

[0013] As an alternative or supplement to any of the above embodiments, the drug-coated medical device includes a drug-coated balloon.

[0014] As an alternative or in addition to any of the above embodiments, after the medicated medical device is placed in the closed chamber, the medicated medical device is removed from the chamber and sterilized.

[0015] A drug-coated medical device is disclosed. The drug-coated medical device comprises: an elongated catheter shaft having a distal region; an expandable balloon connected to the distal region, the expandable balloon having an outer surface; and a steam annealed coating disposed along the outer surface; wherein the coating contains everolimus.

[0016] As an alternative or in addition to any of the above embodiments, the vapor annealed coating is free of polymer.

[0017] As an alternative or in addition to any of the above embodiments, the steam annealed coating comprises an excipient.

[0018] As an alternative or addition to any of the above embodiments, the excipient comprises acetyltributyl citrate.

[0019] As an alternative or addition to any of the above embodiments, the vapor-annealed coating is vapor-annealed using isopropyl alcohol.

[0020] A method for treating a medical device is disclosed, comprising: forming a vapor annealing chamber by placing a layer of isopropyl alcohol in a container and allowing the layer of isopropyl alcohol to partially evaporate to reach liquid-vapor equilibrium; placing a balloon coated with everolimus in the vapor annealing chamber; vapor annealing the balloon coated with everolimus in the vapor annealing chamber; and removing the vapor annealed balloon coated with everolimus from the vapor annealing chamber.

[0021] Alternatively or additionally to any of the above embodiments, placing the everolimus-coated balloon in a steam annealing chamber includes placing the everolimus-coated balloon in a steam annealing chamber when the balloon is in a folded configuration.

[0022] Alternatively or additionally to any of the above embodiments, placing the everolimus-coated balloon in a vapor annealing chamber includes placing the everolimus-coated balloon in a vapor annealing chamber when the balloon is in an inflated configuration.

[0023] As an alternative or in addition to any of the above embodiments, after the steam-annealed everolimus-coated balloon is removed from the steam-annealing chamber, the steam-annealed everolimus-coated balloon is sterilized.

[0024] The above summary of some embodiments is not intended to describe each disclosed embodiment or every implementation of the present disclosure. The following figures and detailed description will more particularly illustrate these embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present disclosure may be more fully understood upon consideration of the following detailed description in conjunction with the accompanying drawings, in which:

[0026] Figure 1 is a schematic diagram of an example medical device.

[0027] Figure 2 is a schematic diagram of an example medical device.

[0028] Figure 3-5 An example approach is shown.

[0029] Although the present disclosure may be modified in various ways and have alternative forms, the specific embodiments shown by way of example in the accompanying drawings will be described in detail below. However, it should be understood that the intent of the present invention is not limited to the specific embodiments described. On the contrary, the intent of the present invention is to cover all modifications, equivalents and alternatives, as long as they are within the spirit and scope of the present disclosure. DETAILED DESCRIPTION

[0030] For the following defined terms, these definitions shall apply unless a different definition is given in the claims or elsewhere in this specification.

[0031] All numerical values ​​mentioned in this specification are assumed to be modified by the word "about", whether or not explicitly stated. The word "about" generally refers to a range of numerical values ​​that are considered by those skilled in the art to be equivalent to the cited numerical value (e.g., having the same function or result). In many cases, the word "about" may include numerical values ​​rounded to the nearest significant figure.

[0032] The recitation of numerical ranges by endpoints includes all numbers within that range (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0033] In this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the content clearly dictates otherwise. In this specification and the appended claims, the term "or" is generally used in its sense including "and / or" unless the content clearly dictates otherwise.

[0034] It should be noted that references in the specification to "an embodiment," "some embodiments," "other embodiments," etc. indicate that the described embodiments may include one or more specific features, structures, and / or characteristics. However, such references do not necessarily mean that all embodiments include the specific features, structures, and / or characteristics. In addition, when specific features, structures, and / or characteristics are described in connection with one embodiment, it should be understood that these features, structures, and / or characteristics may also be used in connection with other embodiments, whether or not explicitly described, unless explicitly stated to the contrary.

[0035] The following detailed description should be read together with the attached Figure 1 Similar elements in different drawings are numbered the same when read together. The drawings, which are not necessarily drawn to scale, depict illustrative embodiments and are not intended to limit the scope of the invention.

[0036] Medical devices coated with drugs, such as drug-coated stents, drug-coated balloons, etc., can be used to treat small vessel occlusions and / or vascular diseases. Some example drugs that can be used with these devices include paclitaxel, everolimus, sirolimus, etc. Applying the drug to the medical device may include applying a crystalline form of the drug to the surface of the medical device. In at least some cases, the manufacturing process may include converting an amorphous form of the drug into a crystalline form. For example, crystalline everolimus (e.g., everolimus crystals) can be applied to the surface of a medical device and then converted to an amorphous form. It may be desirable to modify the coating morphology, for example to improve the durability and / or drug delivery capability of the coating. Disclosed herein is a process for improving coating durability and / or drug delivery capability.

[0037] A variety of coating processes are contemplated. For example, some exemplary processes for converting an amorphous form of a drug into a crystalline form generally include (a) preparing a suitable solvent, (b) preparing a nucleation initiator with the solvent, (c) combining / mixing the nucleation initiator with the amorphous form of the drug to form a prodrug dispersion / suspension, and (d) incubating the prodrug dispersion / suspension to convert the amorphous form of the drug into the crystalline form of the drug. The use of a suitable surfactant in the prodrug dispersion / suspension can allow the formation of drug crystals having a desired morphology, allow the formation of drug crystals having a desired size and / or shape and / or aspect ratio, allow the formation of a coating suspension having a desired stability, combinations thereof, and the like. Thus, at least some processes for converting an amorphous form of a drug into a crystalline form include (a) preparing a suitable solvent, (b) preparing a surfactant solution by combining / mixing a surfactant with the solvent, (c) preparing a nucleation initiator with the solvent, (d) combining / mixing the nucleation initiator with the surfactant solution and the amorphous form of the drug to form a prodrug dispersion / suspension, and (e) incubating the prodrug dispersion / suspension to convert the amorphous form of the drug into the crystalline form of the drug.

[0038] In some embodiments, the drug may be a macrolide immunosuppressant (limus) drug. In some embodiments, the macrolide immunosuppressant is rapamycin, biotin (biotin A9), 40-O-(2-hydroxyethyl) rapamycin (everolimus), 40-O-benzyl-rapamycin, 40-O-(4'-hydroxymethyl) benzyl-rapamycin, 40-O-[4'-(1,2-dihydroxyethyl)] benzyl-rapamycin, 40-O-allyl-rapamycin, 40-O-[3'-(2,2-dimethyl-1,3-dioxolan-4(S)-yl)-prop-2'-ene-1'-yl]-rapamycin, (2':E,4'S)-40-O-(4',5'-dihydroxypent-2'-ene-1' -yl)-rapamycin 40-O-(2-hydroxy)ethoxycarbonylmethyl-rapamycin, 40-O-(3-hydroxy)propyl-rapamycin 40-O-(6-hydroxy)hexyl-rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin 40-O-[(3S)-2,2-dimethyldioxolan-3-yl]methyl-rapamycin, 40-O-[(2S)-2,3-dihydroxyprop-1-yl]-rapamycin, 40-O-(2-acetoxy)ethyl-rapamycin 40-O-(2-nicotinoyloxy)ethyl-rapamycin, 40-O-[2-(N-morpholino)acetoxy]ethyl-rapamycin 4 0-O-(2-N-imidazolylacetoxy)ethyl-rapamycin, 40-O-[2-(N-methyl-N'-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-demethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-dihydro-40-O-(2-hydroxy)ethyl-rapamycin, 28-O-methyl-rapamycin, 40-O-(2-aminoethyl)-rapamycin, 40-O-(2-acetylaminoethyl)-rapamycin 40-O-(2-nicotinoylaminoethyl)-rapamycin, 40-O-(2-(N-methyl-imidazol-2'-ylcarboxymethoxyamino)ethyl)-rapamycin Rapamycin, 40-O-(2-ethoxycarbonylaminoethyl)-rapamycin, 40-O-(2-toluenesulfonylaminoethyl)-rapamycin, 40-O-[2-(4',5'-dicarboxyethoxy-1',2',3'-triazol-1'-yl)-ethyl]-rapamycin, 42-epi-(tetrazolyl)rapamycin (tacrolimus), 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid]rapamycin (temsirolimus), (42S)-42-deoxy-42-(1H-tetrazol-1-yl)-rapamycin (zotarolimus), or derivatives, isomers, racemates, enantiomers, prodrugs, hydrates, esters or analogs thereof.Other drugs include anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogens, sulfadiazine, mesalamine and their analogs; anti-neoplastic / anti-proliferative / anti-mitotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, thymidine kinase inhibitors and their analogs; anesthetics such as lidocaine, bupivacaine, ropivacaine and their analogs; anticoagulants; and growth factors.

[0039] As described herein, an exemplary process for converting an amorphous form of a drug into a crystalline form includes preparing a suitable solvent. When the solvent is a single material, preparing a suitable solvent can be as simple as placing the solvent in a suitable container. When the solvent is a mixture of multiple materials, preparing a suitable solvent can include combining or mixing solvents.

[0040] In at least some cases, the solvent may include alcohols such as methanol, ethanol (EtOH), isopropanol (IPA), n-butanol, isobutanol or tert-butanol; nitriles such as acetonitrile (ACN); ethers such as tetrahydrofuran (THF), isopropyl ether (IPE), diethyl ether (DEE); ketone solvents such as acetone, 2-butanone (MEK) or methyl isobutyl ketone (MIBK); halogenated solvents such as dichloromethane (DCM), monofluorobenzene (MFB), α, α, α-trifluorotoluene (TFT), nitromethane (NM), ethyl trifluoroacetate (ETFA); alkanes such as hexane, heptane, etc.; aromatic hydrocarbons such as toluene or xylene; and ester solvents such as ethyl acetate. Mixed solvents such as ethyl acetate / heptane, acetone / water, IPA / water, IPA / THF, methanol / water, IPA / heptane or THF / heptane may also be used.

[0041] When a solvent mixture is used, the mixture may have a suitable ratio of each material. For example, some example solvents may include a mixture of ethyl acetate and heptane. The ratio of ethyl acetate to heptane may be between about 1:4 and 1:30, or between about 1:4 and 1:20, or about 1:20. Other mixtures and / or ratios are also contemplated. Therefore, in some cases, the process of converting the amorphous form of the drug into a crystalline form may include preparing a solvent, such as by mixing ethyl acetate with heptane.

[0042] The process of converting an amorphous form of a drug into a crystalline form may include preparing a surfactant solution (e.g., preparing a surfactant solution with a solvent). In at least some cases, the surfactant may include TWEEN 20 TM (e.g., polysorbate 20, polyoxyethylene (20) sorbitan monooleate or PEG (20) sorbitan monooleate), TWEEN 80 TM (e.g., polysorbate 80, polyoxyethylene (80) sorbitan monooleate or PEG (80) sorbitan monooleate), SPANTM 80. SPAN TM 20. TRITON TM X-100, TRITON TM 400, nonionic surfactant, etc. The surfactant solution may have a suitable concentration. For example, the concentration of the surfactant solution may be about 0.01-1% (by weight), about 0.05-0.5% (by weight), or about 0.1% (by weight).

[0043] The process of converting the amorphous form of the drug into a crystalline form may include preparing a nucleation initiator (e.g., preparing the nucleation initiator with a solvent). This process or step may also be referred to as "nucleation". In at least some cases, the nucleation initiator may include a crystalline form of the drug suspended in a suitable solvent (e.g., may or may not be the same solvent used to dissolve the amorphous form of the drug). When the drug used is everolimus, the nucleation initiator may include a suitable amount of everolimus crystals in a suitable solvent. The concentration of everolimus in the solvent may be between about 0.1-10%, or between about 0.1-2%, or about 0.5%. Everolimus crystals may include everolimus microcrystals formed as described herein. Alternatively, everolimus crystals may include everolimus crystals having different morphologies.

[0044] The process of converting the amorphous form (amorphous form) of the drug into a crystalline form can include mixing and / or combining a nucleating initiator with a surfactant solution and the amorphous form of the drug to form a drug precursor dispersion / suspension. The amount of the amorphous form of the drug added can be different. For example, every milliliter (for example, every milliliter of solvent) can add / disperse about 0.5-100 milligrams of everolimus, or every milliliter can add / disperse about 1-50 milligrams of everolimus, or every milliliter can add / disperse about 10-30 milligrams of everolimus, or every milliliter can dissolve about 20 milligrams of everolimus. In at least some cases, the drug dispersion solution can be referred to as and / or be similar to a slurry.

[0045] Incubate the prodrug dispersion / suspension to convert the amorphous form of the drug into a crystalline form. In some cases, incubation can be carried out within a suitable time range of several hours to several days. For example, incubation can last for 24 hours. In these and other cases, incubation may include a high temperature or warm incubation step at a suitable temperature (e.g., about 20°C to 80°C, or about 40°C to 60°C, or about 50°C). In some cases, high temperature incubation may include stirring the prodrug dispersion (e.g., using a suitable device, such as an orbital shaker). However, in other cases, the high temperature incubation step does not include stirring / agitation. The high temperature incubation step may be carried out within a suitable time range of several hours to several days. For example, incubation can last for about two days. In these and other cases, incubation may also include a low temperature or cooling incubation step at a suitable temperature (e.g., about -10°C to 10°C, or about 0°C to 5°C, or about 4°C). The low temperature incubation step may be carried out within a suitable time range of several hours to several days. For example, incubation can last for several days.

[0046] In some cases, a process for converting an amorphous form of a drug into a crystalline form may include (a) filtering the crystalline form of the drug, (b) washing the crystalline form of the drug, and (c) drying the crystalline form of the drug. For example, some processes are contemplated that include filtering, washing, and drying the drug crystals. In doing so, the solvent, surfactant, or both may be substantially completely removed from the drug crystals.

[0047] The crystal form of the drug (e.g., everolimus) formed by this process can result in a crystal morphology, size, and shape that can be described as microcrystals. In particular, a surfactant is used in the crystallization process, and a suitable solvent mixture is mixed in a suitable ratio to result in the formation of microcrystals. For the purposes of this disclosure, microcrystals can be understood as crystals that can be described as relatively flat, thin sheets. Some example sizes can include microcrystals with a width less than about 3 microns (e.g., having a non-zero width less than about 3 microns), a thickness less than about 1 micron (e.g., having a non-zero thickness less than about 1 micron), and a length less than about 10 microns (e.g., having a non-zero length less than about 10 microns). Microcrystals can be desired for a variety of reasons. For example, in some crystallization processes that form "larger", rod-shaped, or "non-micro" crystals, the resulting crystals can settle rapidly when suspended in a coating material / dispersion. This can make it more challenging to apply drug crystals to medical devices. Microcrystals formed by the process described herein can, for example, be suspended in a coating material / dispersion and remain suspended for an extended period of time (e.g., months or longer).

[0048] In some cases, the microcrystals formed by the processes described herein can be suspended in a suitable coating material / dispersion. This can include adding a suitable excipient. An example excipient can include acetyl tributyl citrate (ATBC). In some cases, the drug microcrystals can be mixed with the excipient in a ratio of about 20:80 to about 90:10, or in a ratio of about 80:20. The coating material / dispersion can then be applied to the medical device using a suitable method. For example, the coating material / dispersion can then be applied to the medical device by dipping, rolling, by syringe, etc. Some example drug-coated medical devices such as Figure 1-2 For example, Figure 1 A drug coated balloon device 10 is shown, comprising a balloon 12 coupled to a catheter shaft 14. A drug coating 16 (eg, crystalline everolimus comprising everolimus microcrystals formed as described herein) can be disposed along the balloon 12. Figure 2 A drug coated stent 110 is shown. A drug coating 116 (eg, crystalline everolimus comprising everolimus microcrystals formed as described herein) can be disposed along the stent 110.

[0049] After coating, the drug coated balloon device 10 and / or drug coated stent 110 may be treated and / or further processed to modify the coating morphology (eg, to improve coating durability and / or drug delivery capabilities). Figure 3-5 An exemplary process for treating / modifying the coating morphology is schematically illustrated. An exemplary process is a steam annealing process, wherein the drug coated balloon device 10 and / or the drug coated stent 110 (e.g., Figure 3-5 In FIG. 1 , a drug coated balloon device 10 is shown; however, other devices, including a drug coated stent 110, may undergo a similar process).

[0050] An example vapor annealing process may include forming a vapor annealing chamber by placing an annealing fluid 20 (which may be a volatile substance such as isopropyl alcohol (IPA) for example) in the chamber 18. Figure 3 , a chamber 18 is schematically depicted, and a layer of annealing fluid 20 is placed at the bottom of the chamber 18. Depending on the size of the chamber, the layer of annealing fluid 20 can be about 1-10 mm thick or thicker, or about 1-5 mm thick or thicker, or about 1.5-3 mm thick or thicker, or about 2 mm thick or thicker. Initially, the remaining open space 22 of the chamber 18 can be filled with only air or a controlled atmosphere.

[0051] The annealing fluid 20 may be allowed to at least partially evaporate within the chamber 18 (e.g., when the chamber 18 is closed or sealed) until the annealing fluid 20 reaches liquid-vapor equilibrium, such as Figure 4 For example, Figure 4The chamber 18 depicted in FIG. 1 (e.g., a vapor annealing chamber 18) may include a liquid portion 20a of an annealing fluid 20 and a vapor portion 20b of the annealing fluid 20. The time required to reach liquid-vapor equilibrium may vary and may include about 1-10 hours or more, or about 1-5 hours or more, or about 1.5-3 hours or more, or about 2 hours or more.

[0052] When the annealing fluid 20 reaches a suitable equilibrium, the coated medical device (e.g., drug coated balloon device 10) can be placed in a vapor annealing chamber 18 (e.g., a closed vapor annealing chamber 18), such as Figure 5 As shown. This can include placing the drug coated balloon device 10 in the vapor annealing chamber 18 in a folded configuration, an unfolded configuration, a partially inflated configuration, an inflated configuration, or another suitable configuration. In at least some cases, the drug coated balloon device 10 can be placed in the vapor annealing chamber 18 in a manner to prevent the drug coated balloon device 10 from contacting a layer of the annealing fluid 20 (e.g., the liquid portion 20a of the annealing fluid 20). The drug coated balloon device 10 can be placed in the vapor annealing chamber 18 for a suitable period of time. For example, the drug coated balloon device 10 can be placed in the vapor annealing chamber 18 for about 1-10 hours or more, or about 1-5 hours or more, or about 1.5-3 hours or more, or about 2 hours or more.

[0053] After the steam annealing process, the drug coated balloon device 10 can be removed from the steam annealing chamber 18. In some cases, the drug coated balloon device 10 (e.g., the now steam annealed drug coated balloon device 10) can undergo additional processes, such as folding, placing the drug coated balloon device 10 into a balloon protector, sterilization (e.g., ethylene oxide sterilization), packaging, assembly, etc.

[0054] The drug-coated balloon device 10 (e.g., the drug-coated balloon device 10 now being steam-annealed) can have many desirable properties. For example, a drug-coated medical device that has not been steam-annealed can have a dry, powdery drug layer morphology. In contrast, the drug-coated balloon device 10 (e.g., the drug-coated balloon device 10 now being steam-annealed) can have a similar wet, smooth drug layer morphology. The drug layer can also have improved durability and / or improved drug delivery capabilities (e.g., compared to a drug layer that has not been steam-annealed).

[0055] It should be understood that the present disclosure is in many respects illustrative only. Changes may be made to the details, particularly in shape, size, and arrangement of steps, without exceeding the scope of the present disclosure. This may include, where appropriate, using any feature of an example embodiment for other embodiments. Of course, the scope of the present invention is defined by the language of the appended claims.

Claims

1. A method for processing a medical device, the method comprising: placing an annealing fluid in the closed chamber; Allowing the annealing fluid to reach liquid-gas equilibrium in the chamber; as well as A medical device coated with a drug is placed in the closed chamber.

2. The method of claim 1, wherein the annealing fluid comprises isopropyl alcohol.

3. The method of any one of claims 1 to 2, wherein the closed container has a substrate, and placing an annealing fluid in the closed chamber comprises coating the substrate with the annealing fluid.

4. The method of claim 3, wherein coating the substrate with the annealing fluid comprises coating the substrate to form a 1-10 mm thick layer of annealing fluid. 5 . The method of claim 1 , wherein bringing the annealing fluid to liquid-vapor equilibrium within the chamber comprises partially evaporating the annealing fluid.

6. The method of any one of claims 1 to 5, wherein allowing the annealing fluid to reach liquid-vapor equilibrium within the chamber comprises partially evaporating the annealing fluid for at least two hours.

7. The method of any one of claims 1 to 6, wherein placing the medicated medical device in the closed chamber comprises placing the medicated medical device in the closed chamber for at least two hours.

8. The method of any one of claims 1 to 7, wherein the drug-coated medical device comprises a drug coating, and placing the drug-coated medical device within the closed chamber comprises vapor annealing the drug coating.

9. The method of claim 8, wherein the drug coating comprises everolimus.

10. The method of any one of claims 1 to 9, wherein the drug-coated medical device comprises a drug-coated balloon.

11. The method of any one of claims 1 to 10, wherein after placing the medicated medical device in the closed chamber, the medicated medical device is removed from the chamber and sterilized.

12. A medical device coated with a drug, comprising: an elongated catheter shaft having a distal region; an expandable balloon coupled to the distal region, the expandable balloon having an outer surface; a vapor annealed coating disposed along said exterior surface; and wherein the coating comprises everolimus.

13. The medicated medical device of claim 12, wherein the vapor annealed coating is free of polymer.

14. The drug-coated medical device of any one of claims 12 to 13, wherein the vapor-annealed coating comprises an acetyltributyl citrate excipient.

15. The medicated medical device of any one of claims 12 to 14, wherein the vapor-annealed coating is vapor-annealed with isopropyl alcohol.

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