FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"Antibiotic eluting orthopedic implant and method of preparation thereof"
2. APPLICANT:
1. (a) NAME : MATRIX MEDITEC PVT LTD
(b) NATIONALITY : An Indian
(c) ADDRESS : 34 Saket Industrial Estate
Moraiya Changodar Ahmedabad 382210 Gujarat India
3. PREMABLE TO THE DESCRIPTION
COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.

The present invention relates to an antibiotic eluting implant and method of preparing thereof. More particularly the present invention relates to an antibiotic coated on implant in which mixture of atleast one antibiotic and biodegradable polymer matrix is coated on implant as first layer. The antibiotic and biodegradable formulations prove to be effective preventive therapeutic modalities in implant-related infections. It is further coated with biodegradable polymer as a second layer. The protective layer of top drug free diffusing polymer layer prevent underlying layer from moisture, light and premature drug release. This top drug free polymer layer allow prolonged levels of antibiotic in local tissues after local administration compare to implant coated with only drug polymer matrix.
BACKGROUND OF INVENTION:
Various devices are often implanted into the body of a human or an animal for orthopedic purposes to strengthen bones, fasten portions of a bone to correct a fracture and replace joints.
Infection is the most common serious complication of every surgical implant. Musculoskeletal sepsis is a chronic debilitating disease. Staphylococcus aureus is the most common pathogen, followed by Pseudomonas species in 16% of cases. Several studies indicate that Staphylococcus epidermidis staphylococcus aureus, and Enterococci are the most common organisms causing infection of the implants. Almost half of the 2 million cases of nosocomial infections that occur each year in the US and worldwide are associated with indwelling medical devices [Darouiche RO, Treatment of infections associated with surgical implants, N Engl J Med, 2004; 350:1422-9 and Whitehouse JD, Friedman ND, Kirkland KB, et al., The impact of surgical-site infections following orthopaedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost, Infect Control Hosp Epidemiol, 2002; 23:183-9]. Chronic osteomyelitis is a result of either bacterial contamination in compound

fractures or of infection following operative stabilization of fractures by intramedular (IM) nailing or plating and other orthopedic operations such as alloplastic joint replacement. The most common type of chronic osteomyelitis is due to infected osteosynthesis (49%), followed by open fractures (29%), and haematogenous osteomyelitis (22%) (Galey and Uhthoff). Furthermore, the incidence of musculoskeletal infection is higher among relatively young individuals, probably because of their susceptibility to open fractures and subsequent complications. However, infections associated with surgical implants are generally more cumbersome to manage, have a greater adverse impact on quality of life, result in excessive prolongation of hospital stays, and incur higher costs [Boxma H, Broekhuizen T, Patka P, Oosting H. Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch Trauma Trial, Lancet 1996; 347:1133-7 and Whitehouse JD, Friedman ND, Kirkland KB, et al., The impact of surgical-site infections following orthopaedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost, Infect Control Hosp Epidemiol, 2002; 23:183-9]. It is critical to implement optimal strategies for preventing infection. Antimicrobial approaches are intended to prevent implant-associated infections by impeding bacterial adherence to the implant surface and/or reducing the concentration of bacteria in the immediate vicinity of the implant. Potentially protective strategies include systemic peri-operative antibiotic and local antimicrobial prophylaxis (using antibiotics or antiseptics). Antimicrobial agents can be locally applied in various forms, including skin antisepsis, antimicrobial irrigation of the surgical field, placement of antimicrobial carriers, dipping of surgical implants in antimicrobial solutions, and inserting antimicrobial-coated implants.
This protective strategy is largely based on the principle that bacterial colonization of the surgical implant is a prelude to clinical infection. Most cases of implant-related infection that clinically manifest within 1 year of surgical placement are

thought to result from perioperative inoculation of pathogens. The major purpose of local antibiotic prophylaxis is to prevent organisms from colonizing the implant and/or contaminating the tissues adjacent to the implant. As with antimicrobial irrigation of the surgical field, the approach of dipping implants in antimicrobial solution has no established method of application and results in an undetermined amount of locally available antimicrobial drugs. Surgeons are continually struggling to reduce orthopedic infections, but no current available treatment offers minimization of side effects with maximum effectiveness in product. Presently surgeons are generally dipping the implants in anti-bacterial drug solution just before the surgery to prevent any chances of infection at local surgery side. This gives only few minutes to drug elution and effect at injured side. And to compensate this after surgery, doctors are giving drugs (for few months) either orally (tablet form) or parentally (injection form) to patients for further minimize infection chances. However, the dipping approach incorporates relatively smaller amounts of antimicrobial drugs onto the surface of the implant, which explains the low likelihood for detecting systemic antimicrobial levels and the short duration (a few hours) of local antimicrobial activity [Preventing infection in surgical implants a report by Rabih O Darouiche, MD Center for Prostheses Infection and Infectious disease section, Veterans affairs medical center and baylor college of medicine].
Patent application US10955777 discloses antimicrobial huyluronic acid coatings for orthopedic implants in which implants are coated with hyaluronic acid and its derivatives to resist antimicrobial growth. It is further coated with therapeutic agent i.e. antibiotic. But in this invention there is lack of protective layer over the antibiotic layer.
Patent application US10521455 discloses implant having a long term antibiotic effect in which implants are coated with polymer and metallic silver situated on the polymer material and underneath the coating causes complications in case of degradation as the polymer uses in the invention is not a biodegradable polymer.

Thus there is an instant need of such type of implant which have least complications and efficient sustain release of an antibiotic to avoid the risks after implantation.
OBJECT OF THE INVENTION
The main object of the invention is to provide antibiotic eluting implant and preparation thereof.
Another object of the invention is to provide coating of antibiotic on implant surface with the help of biodegradable carrier and top layer of polymer provide sustain antibiotic release profile compare to implants coated with only drug and polymer matrix.
Yet another object of the invention is to provide antibiotic eluting implant which has advantages of an established method of antimicrobial application, a known amount of locally available antimicrobials, a low likelihood of detectable systemic antimicrobial levels and a relatively persistent local antimicrobial activity of several weeks.
SUMMARY OF INVENTION
The present invention deals with antibiotic eluting implant. An antibiotic eluting implant acts as solution to overcome the risk of infection after implantation. Implants are coated with a combination of antibiotic drug and biodegradable polymeric as first layer and biodegradable polymer as a second layer. The present invention also discloses preparation of the said implant. The process for preparing antibiotic eluting implant comprises, preparing the solutions; coating and drying of the implant; sterilizing the implant and finally packaging of the implant.
BRIEF DESCRIPTION OF DRAWINGS

Figure 1 shows % cumulative drug release profile of gentamicine eluting orthopedic implant.
Figure 2 (a) shows standard, fibroblast cells after contact with extract of drug loaded implant sample 1.
Figure 2 (b) shows standard fibroblast cells after contact with extract of drug loaded implant sample 2.
Figure 3 (a) shows in-vitro antimicrobial activity against S.aureus of the gentamicin impregnated in biodegradable polymeric matrix uncoated implant.
Figure 3 (b) shows in-vitro antimicrobial activity against S.aureus of the gentamicin impregnated in biodegradable polymeric matrix coated implant.
Figure 3 (c) shows in-vitro antimicrobial activity against E.coli of the gentamicin impregnated in biodegradable polymeric matrix uncoated implant
Figure 3 (d) shows in-vitro antimicrobial activity against E.coli of the gentamicin impregnated in biodegradable polymeric matrix coated implant.
Figure 4 shows standard curve used for estimating adhered platelet number.
Figure 5 shows radio images of materials exposed to 125I-PRP and rinsed in phosphate buffered saline.
Figure 6 (a) shows back scattering image, composition mode indicates that the dark portion (left) of the image is more homogenous and having smooth surface than the light portion (right) at 400X magnification.
Figure 6 (b) shows scanning image mode of drug-polymer coated implants. The picture indicates that even at 15000X magnification the coated surface is very homogenous.
Figure 6 (c) shows electron micrographic imaging mode (1000X) (left) polymer and (right) bare SS indicates that coating surface is smoother than metallic surface.
Figure 6 (d) shows back scattering image, topographical mode (250X) also confirms (left) coated surface is smoother than bare (right) metallic surface.

Figure 6 (e) shows contamination free surfaces from back scattering image of homogeneously distributed drug + polymer coated implant in topographical mode at 15000X magnification.
Figure 7 (a) shows release amount of drug by without outer layer coating implant on day 1.
Figure 7 (b) shows release amount of drug by without outer layer coating implant on day 2.
Figure 7 (c) shows release amount of drug by without outer layer coating implant on day 3.
Figure 7 (d) shows release amount of drug by without outer layer coating implant on day 4.
Figure 7 (e) shows release amount of drug by without outer layer coating implant on day 7.
Figure 7 (f) shows release amount of drug by without outer layer coating implant on day 14.
Figure 8 (a) shows release amount of drug by present invention implant on day 1.
Figure 8 (b) shows release amount of drug by present invention implant on day 2.
Figure 8 (c) shows release amount of drug by present invention implant on the day 3.
Figure 8 (d) shows release amount of drug by present invention implant on day 4.
Figure 8 (e) shows release amount of drug by present invention implant on day 7.
Figure 8 (f) shows release amount of drug by present invention implant on day 14.

Figure 8 (g) shows release amount of drug by present invention implant on day 21.
Figure 8 (h) shows release amount of drug by present invention implant on day
28.
DETAIL DESCRIPTION
The nature of invention is clearly described in the specification. The invention has various components and they are clearly described in the following pages of the complete specification.
The present invention contains a drug eluting orthopedic implant in which implant is coated by first layer of an antibiotic with biodegradable polymer dissolved in the solvent and second protective layer of biodegradable polymer. First layer of the antibiotic is formulated to 20+10% of the drug dissolved in distilled water with biodegradable polymer of 80+10% dissolved in the appropriate solvent in the base layer of the implant. The second layer is formulated to 40+10% of biodegradable polymer dissolved in appropriate solvent to prevent premature drug release at the time of implantation.
The first layer of antibiotic eluting orthopedic implant comprises antibiotic from the group amino glycosides.
More preferably the first layer of the antibiotic eluting implant comprises antibiotic selected from gentamicin sulphate, aminoglycoside, amikacin/ apramycin, arbekacin, astromicin, bekanamycin, capreomycin, dibekacin, dihydrostreptomycin, elsamitrucin, fosfomycin, G418, gentamicin, hygromycin B, isepamicin, kanamycin, kasugamycin, lividomycin, micronomicin, neamine, neomycin, netilmicin, paromomycin sulfate, ribostamycin, sisomicin, streptoduocin, streptomycin, tobramycin and verdamicin, a biodegradable polymer selected from poly(D, L-lactide),

polyethylene glycol and polypropylene and solvent is selected from acetone, ethyl acetate, chloroform and hexafluoroisopropanol.
The second protective layer comprises the coating of biodegradable polymer selected from poly (D, L-lactide), poly(L-lactide), polyethylene glycol and polypropylene dissolved in the solvent selected from acetone, ethyl acetate, chloroform and hexafluoroisopropanol.
The process for preparation of the implant comprises of the following steps:
1. Antibiotic and biodegradable polymer are dissolved in HPLC grade selected solvents.
2. Implant is held vertically to the implant holding assembly of machine where the spray gun is provided with the gas inlet and the 0.5-mm diameter nozzle outlet and special grade nitrogen gas is supplied via a magnetic valve to the gas inlet.
3. Implants are positioned 4.8 - 5.0 cm distance from the spray nozzle.
4. A suitable volume of drug-polymer solution is taken and transferred to the spray gun feed with the help of automatic pipette. The procedure is repeated until all the solution is sprayed and it is continued until a suitable amount of drug and biodegradable polymer is deposited on the implant.
5. Implant is vacuum dried in ambient conditions for about 1 hour.
6. After vacuum drying of base layer top protective layer of biodegradable polymer is sprayed and again implant is vacuum dried for other 30 minutes.
7. Sterilization of implant is done by EtO sterilization method.
8. Finally the implant is packaged in aluminum foil packs, which in turn are transferred and sealed in PET bags.
All the coating procedure is performed in class 100 clean room having temperature 25±3°C and relative humidity 50±10%. During the spraying N2gas pressure must be maintained between 0.8+5 kg/cm2.

Sterilization of the implant is carried out 60±5°C with relative humidity above 30+10% and a gas concentration between 800mg/l for at least 5-7 hours.
The controlled drug delivery for several weeks after implantation, drug will prevent the device related infections by inhibiting the growth of Gram negative bacteria mainly Staphylococcus aureus. Sustained release of antibiotic from biodegradable polymer coated orthopedic device will reduce the incidences of osteomyelitis, soft tissue swelling and other bone and tissue associated infections. The antibiotic provides high protective levels during the critical perioperative phase to protect the implant from being colonized by possibly inoculated bacteria. This biodegradable polymer excretes from the body via body's natural metabolic actions. In the process of degradation, the polymeric chains are cleaved by hydrolysis and enzymatic degradation process results in decrease of molecular weight to form monomeric acids are eliminated horn the body. Since the soft tissues are not in direct contact with the coated implant due to the polymeric coating, it prevents corrosion up to some extent.
Experiment 1:
20% of an antibiotic gentamicin dissolved in 10 ml distill water with 80% of polymer poly(D, L-lactide) dissolved in 100 ml acetone. Drug solution is added to the polymeric solution drop wise to form a mixture. The said solution was sprayed on implant surface uniformly to form a first layer on the implant. The second protective layer of poly(D, L-lactide) was made by 40% of biodegradable polymer dissolved in 100 ml of solvent sprayed on the base layer. Implants were coated by spray coating method by using indigenous developed drug coating machine. EtO sterilization method was used for sterilizing the strip.
Drug dissolution profile for antibiotic from orthopedic implant:

Gentamicine was liberated with an initial burst of 30-40% for first 3-4 days where the risk of infections was maximum. This initial burst was followed by sustained slow release for prolong period of time of 28 to 30 days maintaining drug levels high enough to bactericidal activity. Figure 1 shows the % cumulative drug release profile of the gentamicin eluting orthopedic implant. Table 1 describes the release profile of gentamicine coated implant.
Table 1: Release profile of gentamicine coated strip

No. Duration Amount released (meg/plate)
1. Dayl 24.88
2. Day 2 59.17
3. Day 3 12.71
4. Day 4 8.75
5. Day 7 49.30
6. Day 14 4.90
7. Day 21 12.45
8. Day 28 35.81
9. Day 35 Not detectable
10. Day 42 Not detectable
Cytocompatibilitv Test:
. The test was conducted non-cytotoxic response towards fibroblast cells. High MIC values were sustained for 3 to 4 days. At the same time, systemic levels of gentamicin remained well below the established toxicity thresholds. For local antibiotic delivery; high local concentrations for a short period of time were achieved but not

result in tissue damage. Most of the gentamicine was removed from the wound by
absorption into the blood stream and excreted in urine. Figure 2 shows fibroblast cells
after contact with extract of drug loaded implant.
Result:
None of the coated implant has shown cytotoxic response.
In-vitro antimicrobial activity test:
The antimicrobial activity of antibiotic eluting orthopedic system was assayed. Staphylococci and E-coli independently grown for 18 h in trypticase soy broth to a concentration of 0.5 MC farland (108). Zone sizes were assayed by measuring the distance to the centre of the tablet pressed in to agar.
Figure 3 shows in-vitro microbial activity, of the gentamicine impregnated in biodegradable polymeric matrix. Gentamicine impregnated microspheres were pressed in to an agar plate overlaid with E.coli and incubated overnight at 37 degree. The tablets had zones of inhibition with diameters of 25.6. Result:
The zone of inhibition was observed around antibiotic coated implant. Conclusion: The implant has antimicrobial activity towards bacteria E.coli and Staphylococcus.
Table 2: Results of residual, residual (acetone), sterility, bioburden, pyrogen test.

No. Test Description Result
1. Residual Metallic screw No peak obtained.
2. Residual (Acetone) Metallic screw No peak obtained.
3. Sterility Metallic screw No growth observed in soyabean casein digest medium and fluid

thiglycollate medium.
4. Bioburden Metallic screw
A. Total bacterial count 100 CFU/2 pieces
B. Total fungal count < 10CFU/2 pieces
5. Pyrogen Metallic screw Complies with IP test using a dose of 10ml of extract/Kg. of rabbits weight of a preparation two metal screws immersed in 100ml of sterile pyrogen free normal saline & kept at 37°C for one hour.
6. Residual EtO Titanium
middle ear prosthesis No peak obtained.
7. Sterility Titanium No growth observed in soyabean
middle ear casein digest medium and fluid
prosthesis thiglycollate medium.
8. Bioburden Titanium
A. Total bacterial count middle ear 40 CFU/2 pieces
B. Total fungal count prosthesis < 10CFU/2 pieces
9. Pyrogen Titanium Complies with IP test using a dose
middle ear of 10ml of extract/Kg.. of rabbits
prosthesis weight of a preparation two metal screws immersed in 100ml of sterile pyrogen free normal saline & kept at 37°C for one hour.

Platelet adhesion:
The platelet adhesion test was done by in-vitro screening of test samples with effect of exposure to platelet rich plasma (PRP). Blood from a human volunteer was collected in to the anti-coagulant. Detection of the platelet adhesion to the test samples was done by radioscintigaphy and platelet consumption was done by Haematology analyzer.
Detection of platelet consumption counts reduction was analyzed by detecting the counts in initial and 30 min samples. Counts detected initially and terminations of exposure are given in the table 3.
Results:
Platelet Consumption:
Table 3: Platelet count data in blood samples before and after exposure to materials.

Sample No: Initial total Final total Percentage
count in count in 2.0 reduction
2.0ml blood ml blood
(x 108) (xl08)
1 4.40 4.12 6.36
2 3.98 3.90 2.01
3 4.54 4.58 -0.88
4 4.26 4.06 4.69
5 4.30 4.02 6.51
Result:
Reduction in platelet count was observed.

Radioscintigraphy:
The test samples after exposure to 125I-PRP are rinsed thoroughly with buffer (PBS) and fixed with 2% glutaraldehyde and imaged. Platelet adhesion to the material surface was quantified with respect to the radioactivity of standard aliquots (serially diluted, known number) of 125I-plateles using the software. Imaging of standard platelet aliquots and adhered platelets on the exposed materials are done simultaneously. Total count of platelets in 2 ml PRP that was exposed to material is 4.28 x 108.
Table 4: platelet number detected on test devices.

Sample ID Number of
Platelets on each
devices Percentage adhered
w.r.t. total platelets in
PRP
1 4973 0.001130
2 4306 0.001082
3, 3448 0.000760
4 5038 0.001183
5 2960 0.000689
Inference: Less than 0.001 % platelets on exposed materials seem to be insignificant platelet adhesion.
Scanning Electron Microscopy Topography:
The samples were prepared by mounting them on the aluminum stub with the carbon paste. The stub was then placed in the SEM chamber. The chamber was evacuated to pressure between 0.5 to 1 Torr. The instrument was operated in ESTM

mode and GSED detector was selected for imaging, SEM images were then taken at 20 KV Accl voltage at various areas at suitable magnification on sample. Observation and Results:
Scanning electron microscopic images (fig.4 (a), (b), (c), (d) and (e)) shows the general feature of antibiotic eluting orthopedic implant. Composition mode indicates two different compositions of the material at the spot of imaging. Conclusion:
SEM Topography indicates the morphology and surface evenness at the place of
polymer drug coating.
Toxicity test:
Test for local effects after implantation in the bone was done. The implantation procedure was carried out to the skin of the anaesthetized rabbits. Rabbits were lightly swabbed using 70% alcohol followed by betadine solution. Cortex region of the femur was exposed and three holes of 2.0mm were drilled. Three test samples were implanted on the left leg femur bone and three control samples on the right leg femur bone. Result:
The general physical conditions of all the experimental animals were normal and none of the animal had shown any abnormality or behavioral changes during the experimental period. Conclusion:
There was no degenerative and necrotic changes and inflammation around the test samples and control samples at one, four and twelve weeks of observation period. The comparative evaluation showed that at one week, the healing pattern is similar in both with moderate inflammation at the host bone implant. At four weeks new woven bone deposition was noted in both groups. Minimal to mild inflammation was observed. At twelve weeks healing of the cavity was observed. Degenerative and necrotic changes were absent in both groups and also neovascularisation was absent.

Histopathology test:
Gross and histopathological evaluation for biocompatibility in the bone was done. Femur bones of the rabbits were received and metaphysic sites were identified in each bone. Cross section of the each site with implants were cut and processed for resin embedding. Sections were stained with Stevenel's blue and examined by light microscopy.
Table 5: observation after gross and histopathology evaluation of an implant.

Period of observation One week Four weeks Twelve weeks
Inflammation in implant Moderate Minimal to mild Absent
Degenerative or necrotic Minimal Absent Absent
changes
Bone regeneration Minimal bone Healing of the Healing of the
deposition and cavity started and cavity was
Moderate thick new bone completed
capsule material direct
observed contact observed
Neovascularisation Absent Absent Absent
Conclusion:
Most of the implants in both protruded above the periosteal aspect and extended deep into at one week and four weeks period. At twelve weeks most of the implants in both groups were in cortex, extended into marrow and periosteum was completely covered by the new bone. The healing time period of one week appeared similar in both groups. Experiment 2:

A comparative study for drug release pattern of the present invention implant and without outer layer coated implant was done by using agar diffusion method to check the gradual release of antibiotic.
• Test sample preparation:
1. Drug coated orthopedic implant (Cortical screw) was taken which was sterilized by Ethylene Oxide (gas sterilization).
2. The screw was transferred into sterile test tube and 3 ml of phosphate buffer (pH-7) was added in the test tube.
3. The test rube was kept closed by the mean of cotton plug and was covered by aluminum foil.
4. The test sample was withdrawn on the pre-decided time period and the released
amount of drug was tested against the standard antibiotic solution.
Test sample preparation remained same for both the sample.
• Inoculation of Test Plates
1. Optimally, within 15 minutes after adjusting the turbidity of the inoculum
suspension, a sterile cotton swab was dipped into the adjusted suspension. The swab was rotated several times and pressed firmly on the inside wall of the tube above the fluid level.
2. The dried surface of a soybean casein digest agar plate was inoculated by streaking
the swab over the entire sterile agar surface. This procedure was repeated by streaking
two more times, rotating the plate approximately 60° each time to ensure an even
distribution of inoculum. Lastly, the rim of the agar was swabbed.
The test was performed to check the released antibiotic from the drug coated implant after 1 day, after 2 days, after 3 days, after 4 days, after 7 days, after 14 days, after 21days and after 28days.

Observation & Result:
Plates were observed after the completion of incubation period for the clear zone of bacterial growth inhibition. Each diameter of the clear zone of bacterial inhibition was measured by zone reader. The unknown concentration of antibiotic released from the drug coated implant was found against the standard antibiotic sample.

Duration Released amount of antibiotic
Without layer coating Test Sample (with outer layer coating)
Day 1 31.3 μg/device 17.11 μg/device
Day 2 42.3 μg/device 38.33 μg/device
Day 3 18.1 μg/device 13.14 μg/device
Day 4 40.2 μg/device 26.1 μg/device
Day 7 33.8 μg/device 18.13 μg/device
Day 14 39.1 μg/device 16.12 μg/device
Day 21 — 25.11 μg/device
Day 28 . — 41.6 μg/device

WE CLAIM:
1. An antibiotic eluting orthopedic implant comprises inner layer and outer layer of coating on orthopedic implant; wherein said inner layer comprises 20+10% of antibiotic dissolved in distilled water and 80+ 10% of a biodegradable polymer dissolved in HPLC grade selected solvent and said outer layer comprises 40+ 10% of biodegradable polymer dissolved in HPLC grade selected solvent.
2. The antibiotic eluting orthopedic implant as claimed in claim 1, wherein antibiotic is from amino glycosides group.
3. The antibiotic eluting orthopedic implant as claimed in claim 2, wherein more preferably antibiotic is selected from group consists of gentamicin sulphate, aminoglycoside, amikacin, apramycin, arbekacin, astromicin, bekanamycin, capreomycin, dibekacin, dihydrostreptomycin, elsamitrucin, fosfomycin, G418, gentamicin, hygromycin B, isepamicin, kanamycin, kasugamycin, lividomycin, micronomicin, neamine, neomycin, netilmicin, paromomycin sulfate, ribostamycin, sisbmicin, streptoduocin, streptomycin, tobramycin and verdamicin.
4. The antibiotic eluting orthopedic implant as claimed in claim 1 wherein the biodegradable polymer is selected from group consists of poly (D, L-lactide), . polyethylene glycol and polypropylene.
5. The antibiotic eluting orthopedic implant as claimed in claim 1 wherein the HPLC grade solvent is selected from the group consists acetone, ethyl acetate, chloroform and hexafluoroisopropanol.

6. A method of preparation of antibiotic eluting orthopedic implant comprises the following steps:
(a) dissolving of antibiotic, and biodegradable polymer in HPLC grade selected solvents;
(b) coating the inner layer on implant by spray drying;
(c) vacuum drying of the inner layer;
(d) dissolving of biodegradable polymer in HPLC grade selected solvents;
(e) coating the outer layer on implant by spray drying;
(f) vacuum drying the outer layer;
(g) sterilizing the implant;
(h) packaging the implant in suitable bags.