Description:FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
THE PATENTS RULES, 2003

COMPLETE SPECIFICATION
[See Section 10, Rule 13]

ACTIVE AGENT COATED MEDICAL DEVICE

SAHAJANAND MEDICAL TECHNOLOGIES LIMITED, A COMPANY REGISTERED UNDER THE LAWS OF INDIA, WHOSE ADDRESS IS SAHAJANAND ESTATE, WAKHARIAWADI, NEAR DABHOLI CHAR RASTA, VED ROAD, SURAT, 395004, GUJARAT, INDIA

THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.
TECHNICAL FIELD
[0001] The present invention relates, generally, to active agent coating or active agent containing coating composition for medical devices and more specifically related to active agent coating or coating compositions comprising active agent along with a suitable excipient for coating the medical devices and a method for preparing the same. The active agent coated medical device are for temporary or permanent deployment inside a lumen such as blood vessels or ducts of a mammal. Specifically, such medical devices are used for site-specific active agent delivery.
BACKGROUND
[0002] Active agent-coated medical devices are used in delivering active agent or active agent-containing matrix (active agent + excipient + optionally, additives) to a target lesion inside the body. Active agent coatings are increasingly used on intravascular devices to facilitate localized active agent delivery and sometimes also aid in easier access and navigation through lumen such as blood vessels. However, recent reports highlight the separation and downstream embolism of polymer particles affecting the vasculature and various organs. Hence, there is a need to improve integrity, uniformity of the coatings and there should be minimal particulate release.
[0003] Active-agent coated medical balloons are a critical sub-domain in the domain of coated medical devices. They may be used to deliver an active agent to a location inside the body, such as to a site within a blood vessel or inside a duct or a tract or a lumen. Medical balloons are used in a wide variety of minimally invasive or percutaneous medical procedures. Usually, the diseased lesion is expanded radially by expansion of the balloon and selected active agent may be delivered through a coating on the perioheral surface of the balloon. Optionally, the coating is placed on a stent and and the stent is used in such procedures. Further, balloons are also customized by modifying the material and design to meet different requirements for cardiovascular, urological, gastrointestinal, neurovascular, and ophthalmic procedures e.g. balloons with pores/ holes for active agent delivery, balloons with scoring elements, balloons of specific geometry etc. On the other hand, a typical balloon can be used for coating an active agent-containing composition on its peripheral outer surface area and the coating composition can be customised to achieve the desired performance. In a nutshell, the goals drive the approach of customization.

[0004] The main challenges in an active agent-coated medical device procedure are active agent loss, particulate release while tracking the balloon to the target lesion and active agent wash-off at the target lesion. Specifically, particulate release should be minimum as this poses a grave and serious risk to the patient. As mentioned above, sometimes, the released particulates get stuck in narrow lumens resulting in amputation or death.
[0005] Therefore, there is a need to develop an active agent based coating composition for medical devices to overcome the abovementioned shortcomings. Hence, it is an objective of the invention to provide an effective active agent based coating composition that may be coated on a suitable medical device in the form of an active agent, an active agent-containing matrix or a combination of active agents to be delivered at the target lesion while minimizing the active agent loss and particulate release while guiding/tracking the balloon to the target lesion. In addition, on deployment of active agent coated medical device, there should be maximum active agent transfer in short contact time and the active agent retention in tissue should be within therapeutic range for sufficient period of time.
[0006]
BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS
[0007] The detailed description is described with reference to the accompanying figures.
FIG. 1 illustrates a FT-IR spectrum chart of an active agent used in the formulation, according to an embodiment of the present invention. The characteristic IR peaks of the coating composition are as follows:
The amorphous form will have single peaks between 1700-1740cm-1.
Anhydrous crystal forms will show two peaks between 1700-1740cm-1.
Dihydrate crystal form will get three or more peaks between 1700-1740cm-1.
FIG. 2 illustrates a comparison of magnified view of surface of active agent-containing formulation coated two commercially available medical devices with surface of active agent-containing formulation coated medical device according to an embodiment of the present invention.
2A: coating in a commercial product A
2B: coating in a commercial product B
2C: coating as per the invention
2D: high magnification (3000X) view of paclitaxel crystals
FIG. 3 illustrates a chart showing particulates released by a medical device while exposed to a simulated physiological environment (ex-vivo) over a period of three minutes, according to an embodiment of the present invention and its comparison with similar profile of two commercially available medical devices.
FIG. 4 illustrates a chart showing active agent retention profile an active agent coating on a medical device in a tissue (ex-vivo) over a period of fourteen days, according to an embodiment of the present invention and its comparison with active agent retention profile of one other commercially available active agent coated medical device.
FIG. 5 illustrates a chart showing an average active agent transfer profile of an active agent coating on a medical device in a tissue (ex-vivo) over a period of three days, according to an embodiment of the present invention.

DESCRIPTION OF THE INVENTION
[0008] The present disclosure provides for an active agent or an active agent composition suitable for coating over a medical device, and designed to be efficiently delivered at a target lesion in a lumen inside a body. The active agent may be coated on the medical device in pure form or the active agent may be dispersed in a matrix (excipient(s) + other additives) to be in the form of a composition or the active agent is in form of a layer in a composite structure.
[0009] In an embodiment, based on the present invention, an outer periphery of the balloon part of a medical device namely a balloon catheter is coated with the active agent or an active agent containing composition. The active agent coated balloon is in folded form and attached to a hollow catheter shaft. Another end of the catheter shaft is attached to a handle that has provisions for inserting a guidewire and for attaching an inflation device. The catheter shaft has a hollow conduit which is connected to a port on the handle to attach the inflation device and the other end of the hollow conduit is attached to the balloon that is expandable in nature. During the procedure, once the active agent coated balloon reaches the target lesion, the operator expands the balloon and the active agent coating coated on the outer periphery of the balloon comes in contact with the tissue wall of a particular artery or a duct. Usually, the diameter of the expanded balloon is higher than the diameter of the artery or duct. Hence, on balloon expansion, the artery or duct also expands and creates tears, micro-fissures in the tissue wall. Some part of the active agent or active agent-containing coating (in particulate form) seeps into these tears and micro-fissures. The active agent then permeates into the tissue wall from these particulates of the active agent or active agent-containing coating. In parallel, a layer of active agent or active agent-containing coating transfers from the balloon and adheres on the tissue wall. The active agent from this layer diffuses and permeates into the tissue wall.
[0010] Each and every constituent of the active agent coating interacts with the tissue wall differently and the combined effect results in the precise properties of the active agent coating. In the entire procedure, while the active agent coated balloon travels from a puncture site (on body of a living being) to the target lesion, some amount of active agent loss occurs from the balloon. Also, on expansion, additional active agent loss, usually called active agent wash-off, occurs due to lose of active agent due to release from fold openings resulting from thestress experienced by the coating due to expansion and due to exposure of the coating to flowing fluids. The active agent of the present invention minimizes these inferior aspects. Further, on contact of active agent or active agent-containing coating with the tissue wall, maximum amount of active agent transfer should take place. Further, the transferred active agent, in the appropriate therapeutic range, is retained in the tissue for a sufficient period of time to cause therapeutic efficacy. The coating composition as per the present invention maximizes these superior aspects.
[0011] A common problem for medical balloons coated with pure active agent coating is that they deliver a less than desirable active agent transfer and which results in insufficient active agent retention due to less compatibility between the active agent and the tissue wall. However, the coating composition of the present invention comprising at least one active agent, along with a suitable excipient and this combination enhances the active agent transfer resulting in the absorbance of the active agent in the tissue wall. The coating composition of the present invention achieves the transfer of the desired amount of active agent onto the tissues without significant active agent loss or any increase in the particulates shedding while tracking the balloon. In addition, there are multiple factors that affect the behavior and performance of a particular active agent-containing coating. Some of the factors are, but not limited to, hydrophobic/hydrophilic or lipophilic/lipophobic nature of different constituents of the coating, molecular weights, crystalline or amorphous nature of the coating.
[0012] A coating formulation for a medical device comprising: at least one active agent; and an excipient comprising a first excipient part , and a second excipient part ; wherein the coating formulation, after drying, results in a semi-crystalline coated layer, and wherein the ratio of the wt.% of active agent to the excipient is in the range of 50:50 to 95:05.

[0013] In an aspect of the present invention, the active agent coating composition can be coated on any medical device which may be an implantable medical device, a temporary implantable device or a non-implantable medical device. This composition has a unique active agent morphology that helps in reducingactive agent loss, and preventing the release of particulates while tracking the balloon. The present invention has an optimized combination of excipients in the active agent coating composition of the present invention enhances active agent transfer and active agent retention in the tissue and also achieves significant reduction in particulate release from the medical device.
[0014] In an aspect of the present invention a method for preparing the active agent coating composition and applying the same on a suitable medical device results in a semi-crystalline coated layer that has better coating integrity.
[0015] In an aspect of the present invention the excipient in the active agent coating composition comprises a combination of a first excipient part and a second excipient part.
[0016] The first excipient part acts like a plasticizer and are low to moderately high molecular weight compounds that help in maintaining coating integrity and enhances active agent transfer to the tissue. Accordingly, the first excipient part contributes in enhancement of the integrity of the coating by enhancing the solubility of the active agent molecules. The second excipient part is typically a low molecular weight non-polymeric compound which acts as a spacer agent between the active agent molecules. They contribute to the reduction in active agent loss during the tracking of a medical device inside a body. The second excipient part is like a spacer agent distinct from the active agent molecules.
[0017] According to the present invention, the first excipient part is selected from, but not limited to, diesters and triesters of acids, glycol-based polymers, sugars, salts, dicarboxylic acids, acids derived from fruits and vegetables and combinations thereof. Specifically, they are selected from a group comprising mannitol, sucrose, sorbitol, xylitol, dextrose, lactose, fructose, citric acid, tartaric acid, acetic acid, adipic acid, fumaric acid, potassium chloride, sodium chloride, polyethylene glycol, propylene glycol, ethylene glycol monoacetate, ethylene glycol diacetate, glycerin, triethyl citrate, tributyl citrate, acetyl triethyl citrate, dibutyl sebacate, diethyl phthalate, dibutyl phthalate and combinations thereof. Further, the nature of the selected first excipient part can be hydrophilic, hydrophobic, lipophilic or lipophobic.

[0018] According to the present invention, the second excipient part is selected from, but is not limited to, surfactants, antioxidants, lipid soluble excipients, vitamins, polar oils, fatty acids, and their derivatives including, but not limited to, ester, amide, halide, nitrile, isocyanate, nitrile, azo, imine, arene, aldehyde, or a combination thereof. Particularly, the second excipient part is selected from a group comprising Tween surfactants, Brij surfactants, Triton surfactants, glyceryl trioleate, a-tocopherol, ß-carotene, propylgallate, butylated hydroxytoluene, ß-hydroxy acid, vitamin A, vitamin B1 to B16, vitamin C, vitamin D, vitamin E, vitamin K, triglycerides, mixed glycerides, vitamin E ester, a-tocopherol ester and combinations thereof. In an embodiment, the second excipient part is a-Tocopheryl acetate.. Further, the nature of the second excipient part can be hydrophilic, hydrophobic, lipophilic or lipophobic.
[0019] According to the present invention, “active agent” refers to any biologically active compound or a pharmaceutical compound or a drug compound that can be used in a composition that is suitable for administration in mammals including humans.
[0020] According to one embodiment of the present disclosure, the active agent of the present invention is an anti-cancer drug, antiproliferation drug, anti-restenosis drugs, neurolytic agents, Quaternary ammonium salts, Sodium channel blockers, anesthetics, amino acids, amines, Calcium channel blockers, diuretics, vasovasorum constrictors, neurotransmitter chemicals, venom, sclerosant agents, anti-nerve growth agents, aminosteroids, neurotoxins, antithrombotics, antioxidants, anticoagulants, antiplatelet agents, thrombolytics, anti-inflammatories, antimitotic, antimicrobial, smooth muscle cell inhibitors, antibiotics, fibrinolytic, immunosuppressive, antiangiogenic, antirestenotic, antineoplastic, antimigrative, anti-antigenic agents, or a combination thereof. Examples of the drug include, but are not limited to, everolimus, sirolimus, pimecrolimus, tacrolimus, zotarolimus, biolimus, paclitaxel, rapamycin and combination thereof. In another embodiment, there can be more than one active agent in the coating to deliver at the target lesion.
[0021] In an aspect of the the present invention , the active-agent containing composition can be coated on a medical device selected from the group consisting of, but not limited to, stent, guide wire, catheter, balloon, heart valve, vena cava filter, vascular graft, a stent graft, bone prosthesis, spine prosthesis, hip prosthesis, rib prosthesis, skull prosthesis, sutures, staples, anastomosis devices, vertebral disks, bone pins, suture anchors, hemostatic barriers, vascular implants, tissue scaffolds, bone substitutes and intraluminal devices. In a particular embodiment, the active agent composition is coated on a medical balloon.
[0022] In an aspect of the present invention, the active agent coating composition can be coated on the medical device through spray coating, dip coating, chemical vapor deposition, physical vapor deposition, Plasma enhanced chemical vapor deposition, evaporating deposition, sputtering deposition, ion plating, atmospheric pressure plasma deposition, sol-gel method and 3-D printing. In an embodiment of the present invention, the active agent is coated on a suitable medical device by spray coating.
[0023] In an aspect of the invention, the medical device to be coated by the active agent composition of the present invention is made of a metal, metallic alloy, non-metal, polymer or a material made of combinations thereof.
[0024] According to another embodiment of the present invention, the active agent coated medical device can be placed inside a lumen or a duct or a tract of a human or animal, such as an artery, vein, bile duct, urinary tract, alimentary tract, tracheobronchial tree, cerebral aqueduct or genitourinary system. Specifically, the medical device can be used endovascularly in renal artery, femoral artery, superficial femoral artery, popliteal artery, tibial artery, genicular artery, cerebral artery, carotid artery, vertebral artery, subclavian artery, radial artery, brachial artery, axillary artery, coronary artery, peripheral artery, iliac artery or neuro-arteries.
[0025] Another aspect of the present disclosure is to provide a method of preparing a coating composition, coating the same on surface of a medical device and drying the same to obtain a semi-crystalline active agent layer with better integrity. The coated layer provides reduced active agent loss and prevents release of particulates while tracking the balloon and enhances active agent transfer and active agent retention in the tissues. The method comprises: (1) preparing a homogeneous solution A of an active agent and a second excipient part in an organic solvent; (2) preparing a solution B of a first excipient part in water; (3) solution B slowly being added into solution A while solution A is being stirred manually, at ambient pressure and temperature; and (4) obtaining a final homogeneous solution or composition for coating on the surface of a medical device. The coating composition comprising the active agent is coated on the medical device using an appropriate coating technique. The wet coating is dried using solvent vapor technique to create active agent crystals in the coating. Drying environment is carefully controlled to control the uniformity of the coated surface and to induce pre-specified extent of crystallinity in the dried coating. Afterwards, the medical device is appropriately packaged and sterilized for application.
[0026] The above explained method to prepare an active agent-containing coating formulation according to the present invention involves a careful selection of solvents, coating process to create uniform coating and drying process to result in A semi-crystalline coating formulation on surface of a medical device. Specifically, the drying process is controlled to form polymorphic phases of the coating that further comprises a combination of amorphous active agent phase and crystalline active agent phase. By controlling different solvents and ratio of the excipients; the rate of active agent transfer and active agent retention can be controlled, and a customized active agent delivery is achieved.
[0027] As described herein, any concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.
[0028] According to one embodiment of the present invention, the loading of the active agent in the coating composition (after coated on the medical device and in dried form) is in the range of about 50%w/w to 99%w/w, preferably about 60%w/w to 95%w/w, more preferably about 70%w/w to 90%w/w.
[0029] According to one embodiment of the present disclosure, the loading of the first excipient part in the coating composition is in the range of about 0.01%w/w to 30%w/w, preferably about 0.1%w/w to 25%w/w, more preferably about 1%w/w to 20%w/w.
[0030] According to one embodiment of the present invention, the loading of the second excipient part in the coating composition is in the range of about 0.01%w/w to 30%w/w, preferably about 0.1%w/w to 25%w/w, more preferably about 1%w/w to 20%w/w.
[0031] According to one embodiment of the present invention, the ratio (by weight) of the active agent to the sum of the first and the second excipients is in the range of about 50:50 to 95:05, preferably about 60:40 to 95:05, more preferably about 70:30 to 90:10.
[0032] The above aspects are further illustrated in the figures and described in the corresponding description below. It should be noted that the description and figures merely illustrate principles of the present invention. Therefore, various arrangements that encompass the principles of the present invention, although not explicitly described or shown herein, may be devised from the description, and are included within its scope.

[0033] Described herein is an example of preparation of a coating composition as per the present invention and forming a layer of the coating composition on a balloon to form semi-crystalline Paclitaxel coated balloon. For preparation of the coating composition, solution A is prepared using an active agent molecule Paclitaxel, a first excipient part as polyethylene glycol and the second excipient part a-tocopheryl acetate (acetic ester of a-Tocopherol) in an organic solvent (Acetone). The concentration of Paclitaxel in the solution is 0.41 %w/v and the concentration of the second excipient part is is 0.03 %w/v. Another solution B is prepared using the first excipient part polyethylene glycol in water. Solution B is kept in a mixture for a predefined duration to make a homogeneous solution. The concentration of the first excipient part in this solution is 0.06 %w/v. Solution B is slowly being added into solution A, at ambient pressure and temperature, while solution A is being stirred manually to obtain a final homogeneous solution or coating formulation. The coating formulation is coated on a percutaneous transluminal angioplasty (PTA) balloon by spray coating . The wet coating is dried, in a controlled environment, using solvent vapor technique to create active agent crystals in the coating. Controlled environment ensures uniformity of the coated surface and pre-specified extent of crystallinity in the dried coating. The active agent load obtained on the PTA balloon is in the range of 1.8 µg/mm2 to 2.4 µg/mm2. Further, the characterization of the formed coating and performance of the anhydrous semi-crystalline Paclitaxel coated balloon are explained below using the figures provided in this disclosure.
[0034] In another embodiment, the medical device is coated using horizontal spray coating mechanism where the device is rotated on its longitudinal axis and the spray nozzle is moved horizontally on the medical device along its length. Spray coating is carried out at low pressure 0.08 – 0.12 Mpa and at flow rate of 0.15 – 0.25 ml/min. In case of medical devices with flexible peripheral surface e.g. Balloon, the medical device is coated at partial inflated or expanded condition

[0035] FIG. 1 illustrates FT-IR spectrum of a coated layer as per an embodiment according to the present invention. The spectrum clearly shows two peaks between 1700-1740 cm-1 range. Based on common general knowledge and reference study materials in the domain, two peaks in this range confirm that the active agent present in the coated layer is in the anhydrous semi- crystalline form.
[0036] FIG. 2 illustrates magnified views, obtained through Scanning Electron Microscopy (SEM) at 200x magnification, of surface of active agent-containing formulation coated on two commercially available medical devices and surface of active agent-containing formulation coated medical device according to an embodiment of the present invention. It is clearly visible that the coated layer created using the present invention is significantly more uniform in texture. Further, at higher magnification (300x), active agent, here Paclitaxel, crystals are also visible.
[0037] FIG. 3 is a chart showing particulates released by a coated medical device according to an embodiment of the present invention and its comparison with similar particulate release by two other commercially available medical devices. For this comparative study, a coated medical device, according to the present invention, was exposed to a simulated physiological environment (in-vitro) under standard conditions for a period of approximately five minutes. This time period includes: 1. time involved in tracking of the balloon, 2. time required for inflation/deflation of the medical device, and 3. time involved in retrieval of the balloon. The comparison clearly shows that the semi-crystalline coated layer as per the present invention releases significantly lesser particulates while tracking the medical device (balloon here) that also results in reduced active agent loss while tracking as well as during inflation at the target lesion.
[0038] FIG. 4 is a chart showing active agent retention profile of the an active agent coating on a medical device according to an embodiment of the present invention and its comparison with active agent retention profile of one other commercially available active agent coated medical device. For this animal pharmacokinetic study, peripheral artery model (in-vivo; Swine - profunda femoris artery, Superficial femoral artery, and Iliac artery) was designed active agent retention profile was studied for fourteen days. From the chart, it is evident that the active agent coating as per the present invention shows equal or better active agent retention as to a commercially available product over a period of fourteen days. The data also shows enhanced active agent transfer on first day of deployment.
[0039] FIG. 5 is a chart showing an average active agent transfer profile of an active agent coating in a tissue (ex-vivo), according to an embodiment of the present invention. The data presented is an average of six same medical devices with same coating. The medical device used in the experiments is a balloon catheter. The study was performed ex-vivo using a simulated path, biological media and tissue. The active agent coated medical device, balloon here, is inflated in the tissue and amount of active agent in biological media, tissue and on balloon was determined after each experiment. In each experiment, trackability time (to reach the target lesion) was between 5 to 30 seconds and the balloon was kept inflated (single inflation) for 120 seconds. Time taken for inflating the balloon varies from 1 second to 60 seconds. Also, the balloon was overinflated by 15 to 20% over its recommended inflation pressure to put the coated layer under stress. It is evident from the chart that the active agent loss while tracking the balloon is very less and the active agent transferred to the tissue is quite high. In addition, the time durations mentioned above are exemplary in nature and the upper limit and lower limit need not to be followed strictly. They may vary in different situations. However, the effect of the present disclosure will remain similar.
[0040] Hence, the preparation of the active agent coating composition and method for forming a coated layer on a medical device, according to an embodiment of the present invention, results in a semi-crystalline coating formulation that helps in maintaining therapeutic level of active agent in tissues while the coating integrity is not compromised as well. It is achieved using a combination of hydrophilic and lipophilic excipients and controlling the crystallization and drying processes.
[0041] In the above description, for purpose of explanation, specific details are set forth in order to provide an understanding of the present disclosure. It will be apparent, however, to one skilled in the art that the present disclosure may be practiced without these details. One skilled in the art will recognize that embodiments of the present disclosure, one of which is described below, may be incorporated into a number of systems. Further, structures and devices shown in the figures are illustrative of exemplary embodiment of the present disclosure and are meant to avoid obscuring the present disclosure.
, Claims:
1. A coating composition for a medical device comprising:
at least one active agent;
a first excipient part and a second excipient part
wherein the coating composition is semi-crystalline, and
the ratio of the wt.% of active agent to the sum of the first excipient part and the second excipient part is in the range of 50:50 to 95:05.

2. The coating composition as claimed in claim 1, wherein the active agent concentration in the coating composition is in a range of 50% w/w to 99% w/w.

3. The coating composition as claimed in claim 1, wherein the first excipient part concentration is between 0.01% w/w to 30% w/w.

4. The coating composition as claimed in claim 1, wherein the second excipient part concentration is between 0.01% w/w to 30% w/w.

5. The coating composition as claimed in claim 1, wherein the active agent is selected from a group comprising antithrombotics, antioxidants, anticoagulants, antiplatelet agents, thrombolytics, antiproliferatives, anti-inflammatories, antimitotic, antimicrobial, smooth muscle cell inhibitors, antibiotics, fibrinolytic, immunosuppressive, antiangiogenic, antirestenotic antineoplastic, antimigrative, anti-antigenic agents, anti-cancer active agent, lipophilic active agent, anti-restenosis active agents, Neurolytic agents, Quaternary ammonium salts, Sodium Channel Blockers, Anesthetics, Amino Acids, Amines, Calcium Channel Blockers, Diuretics, Vasovasorum Constrictors, Neurotransmitter Chemicals, Venom, Sclerosant Agents, Anti-Nerve Growth Agents, Aminosteroids, Neurotoxins, hydrophobic active agent or combinations thereof.

6. The coating composition as claimed in claim 1, wherein the active agent is selected from a group comprising paclitaxel, sirolimus, rapamycin, everolimus, pimecrolimus, tacrolimus, zotarolimus, biolimus, or combinations thereof.

7. The coating composition as claimed in claim 1, wherein the first excipient part is selected from a group comprising diesters and triesters of acids, glycol-based polymers, sugars, salts, dicarboxylic acids, acids derived from fruits and vegetables and combinations thereof.

8. The coating composition as claimed in claim 7, wherein the first excipient part is selected from a group comprising mannitol, sucrose, sorbitol, xylitol, dextrose, lactose, fructose, citric acid, tartaric acid, acetic acid, adipic acid, fumaric acid, potassium chloride, sodium chloride, polyethylene glycol, propylene glycol, ethylene glycol monoacetate, ethylene glycol diacetate, glycerin, triethyl citrate, tributyl citrate, acetyl triethyl citrate, dibutyl sebacate, diethyl phthalate, dibutyl phthalate and combinations thereof.

9. The coating composition as claimed in claim 1, wherein the second excipient part is selected from a group comprising surfactants, antioxidants, lipid soluble excipients, vitamins, polar oils, fatty acids, their derivatives and combinations thereof.

10. The coating composition as claimed in claim 9, wherein the second excipient part is selected from a group comprising polyoxyethylene 20, Tween 85, glyceryl trioleate, a-tocopherol, ß-carotene, propylgallate, butylated hydroxytoluene, ß-hydroxy acid, vitamin A, vitamin B1 to B16, vitamin C, vitamin D, vitamin E, vitamin K, triglycerides, mixed glycerides, vitamin E ester, a-tocopherol ester, and combinations thereof.

11. The coating composition as claimed in claim 1, wherein the first excipient part is polyethylene glycol and the second excipient part is a-Tocopheryl acetate.

12. A medical device coated with the coating composition as claimed in claim 1, wherein the medical device is either an implantable medical device, a temporary implantable device or a non-implantable medical device.

13. The medical device as claimed in claim 12, wherein the medical device is made of a metal, metallic alloy, non-metal, polymer and of combinations thereof.

14. The medical device as claimed in claim 12, wherein the coating composition is placed on a medical device selected from a group comprising a stent, guide wire, catheter, balloon, heart valve, vena cava filter, vascular graft, a stent graft, bone prosthesis, spine prosthesis, hip prosthesis, rib prosthesis, skull prosthesis, sutures, staples, anastomosis devices, vertebral disks, bone pins, suture anchors, hemostatic barriers, vascular implants, tissue scaffolds, bone substitutes and intraluminal devices.

15. The medical device as claimed in claim 12, wherein the medical device is coated by any one of the methods including spray coating, dip coating, chemical vapor deposition, physical vapor deposition, Plasma enhanced chemical vapor deposition, evaporating deposition, sputtering deposition, ion plating, atmospheric pressure plasma deposition, sol-gel method or 3-D printing.

16. A method to prepare a medical device coated with a coating composition, comprising the steps of:
Preparing a first solution of an active agent and a second excipient part in an organic solvent;
Preparing an aqueous solution of a suitable first excipient part;
mixing the aqueous solution in the organic solution to prepare a coating formulation;
spray coating the formulation on a surface of a medical device; and
drying the coated solution in a controlled environment to obtain a semi-crystalline coating layer.

17. The method to prepare an active agent coated medical device as claimed in claim 16, wherein the organic solvent is selected from Acetone, Methyl chloride, Ethylene dichloride, Acetophenone, Ethylene carbonate, Propylene 1,2 carbonate, Methanol, Ethanol, Allyl alcohol, 1-Propanol, 2-Propanol, 1-Butanol, 2-Butanol, Isobutanol, Benzyl alcohol, Cyclohexanol, 1 -Decanol, acetonitrile, Ethanolamine, Nitromethane or combinations thereof.