Stable vancomycin solutions

Abstract

The present disclosure relates to stable aqueous solutions of vancomycin or its pharmaceutically acceptable salt, that are ready to administer to the patient, and those that can be diluted with a suitable diluent, prior to administration.

Description

[0001] STABLE VANCOMYCIN SOLUTIONS

[0002] FIELD OF THE INVENTION

[0003] The present disclosure relates to stable aqueous solutions of vancomycin or its pharmaceutically acceptable salts, that are ready to administer intravenously to the patient, and those that can be diluted with a suitable diluent, prior to administration. The solutions are therefore easy to prepare and administer, and save significant time of the healthcare personnel, while avoiding or reducing any manual errors in preparing the correct doses for intravenous administration.

[0004] BACKGROUND OF THE INVENTION

[0005] Vancomycin is a tricyclic glycopeptide antibiotic drug derived from Amycolatopsis orientalis (formerly Nocardia orientalis). The molecular formula is C66H75C12N9O24«HC1 and the molecular weight is 1 ,485.71. Vancomycin hydrochloride has the following structural formula:

[0006] Vancomycin is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam -resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is indicated for initial therapy when methicillin resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly. Vancomycin is effective in the treatment of staphylococcal endocarditis. Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.

[0007] Vancomycin has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by Streptococcus viridans or .S', bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin has been reported to be effective only in combination with an aminoglycoside. Vancomycin has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin has been used successfully in combination with either rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by .S', epidermidis or diphtheroids.

[0008] Currently, vancomycin is available in the form of solution for oral administration, powder for reconstitution (for intravenous administration), and ready-to-use solution for administration from Xellia Pharmaceuticals (NDA # 211962).

[0009] United States Patent 10,039,804 and family (Xellia Pharmaceuticals) discloses (covers the product approved under NDA # 211962) an aqueous pharmaceutical composition comprising vancomycin and N-acetyl-D-Alanine, wherein the molar ratio of N-acetyl-D-Alanine to vancomycin is from about 1: 1 to about 40: 1, and wherein the composition comprises about 0.5% w / v of vancomycin. The compositions further were disclosed to contain one or more amino acids selected from D-Serine, D-Leucine, D-Valine, L-Lysine, D-Lysine, L-Arginine, D-Omithine and L-Omithine, and have a pH in the range of 3-6. There is nothing in these family of disclosures about vancomycin compositions that do not use N-acetyl-D-Alanine, or that such solutions can be obtained without N-acetyl-D-Alanine.

[0010] United States Patent 10,729,708 and family (Xellia Pharmaceuticals) discloses liquid pharmaceutical composition comprising Vancomycin and sulfobutylether-betacyclodextrin, where the concentration of Vancomycin in the formulation is about from 0.5% to 10% w / v, and wherein the pharmaceutical composition is stable for at least about four weeks at 25°C in a closed container. Cyclodextrin is an essential element of the compositions disclosed here, and no other means to obtain vancomycin solutions is taught.

[0011] United States Patent Publication 20220133844 and family (Somerset Therapeutics) discloses a liquid composition comprising: (a) one or more glycopeptide antibiotics or a pharmaceutically acceptable salt thereof in an amount of about 0. 1% by weight to about 1.0% by weight, (b) N- acetyl -methionine in an amount of about 0. 1% by weight to about 5.0% by weight, and (c) one or more pharmaceutically acceptable excipients. All compositions taught here require the use of N-acetyl-methionine to obtain solutions of vancomycin. No other means are taught or disclosed or suggested.

[0012] United States Patent 10,376,560 (Latitude Pharmaceuticals Inc) discloses a clear and injectable solution composition comprising (a) a glycopeptide selected from the group consisting of vancomycin, norvancomycin or salts thereof, at a concentration of about 0.1% w / v to about 12% w / v; (b) tryptophan selected from the group consisting of the L-form, the D-form, a mixture of the L- and D-forms or salts thereof, at a concentration between about 0.1% w / v to 2.5% w / v, wherein tryptophan inhibits formation of crystalline degradation product-1 (CDP- 1); (c) water, wherein the pH of the solution composition is between about 3 to about 6; and CDP-1 is no more than 4% based on high performance liquid chromatography (HPLC) peak area after storage at 2-8° C for 20 months. The use of tryptophan is important to obtaining solutions disclosed here.

[0013] United States Patent 10,376,559 (Scidose LLP) discloses liquid vancomycin-containing compositions consisting of from about 50 mg / mL to about 250 mg / mL of vancomycin or a pharmaceutically acceptable salt thereof, glycerol, a member of the group consisting of lactic acid, lactate or mixtures thereof, a base and a pharmaceutically acceptable fluid containing water, wherein the composition has a pH of from about 5.5 to about 6.5. There is no teaching or suggestion for obtaining vancomycin compositions other than those specifically disclosed.

[0014] JP11080021 discloses vancomycin injection solutions comprising water, vancomycin and 0.1- 10 wt % amino acids to inhibit color formation. While glycine is mentioned as one of the amino acids that can be used as the amino acid, all working examples in the specification that contain glycine are to freeze-dried compositions. Solution compositions of vancomycin with glycine are not disclosed, and there is no discussion on the stability of the solutions, or their shelf-life, except to state that there is no coloring. Further, there is no teaching or guidance on the pH of the solution and / or its impact on stability of the solution. There is no teaching in JP11080021 that would lead a skilled person to provide stable aqueous solutions of vancomycin that contain glycine, and that are stable over a shelf-life of at least 12 months. DRL’s US 20140155320 discloses compositions containing phospholipid and oil, while Insmed’s US 10471149 discloses stabilized lipid-based glycopeptide antibiotic compositions. Ever Valinject’s WO2022129263 discloses compositions of vancomycin obtained using N- propionylated alanine, and WO2022129264 discloses compositions that use N-acetylated D- cysteine as an essential component. Some other disclosures such as US20210308164 teach use of fat soluble vitamins, or prohormone such as Vitamin D3 to provide compositions of vancomycin, while Eli Lilly’s WO1997019690 discloses a solution of vancomycin hydrochloride comprising between about 0.5% and about 12% w / v vancomycin hydrochloride and between about 0.5% and about 30% v / v. Vanderbilt University’s US4670258 discloses a sterile aqueous solution of vancomycin dissolved therein together with a peptide containing from two to three amino acid residues. US 8778873 discloses a stability study for a combination of Ceftriazone and Vancomycin at pH 8.8, wherein L-arginine, L-Lysine and L-Histidine are used as compatibility / stabilizing agent. WO2014085526 discloses stabilized lipid-based vancomycin compositions wherein amino acids or derivatives thereof stabilize Vancomycin.

[0015] Arecor’s WO2023223053 teaches storage stable aqueous solution composition comprising vancomycin or a pharmaceutically acceptable salt thereof, D-lactic acid or a pharmaceutically acceptable salt thereof; and a polyol selected from the group consisting of propylene glycol, sucrose, glycerol, trehalose, lactose, glucose, sorbitol and mannitol, or a mixture thereof; wherein the osmolarity of the composition is 400-1250 mOsm / L.

[0016] There is prior art describing solutions of vancomycin for ophthalmic, use as solutions for instillation or for injection in the eye. These formulations are specifically designed for ophthalmic use and cannot be used as is for intravenous administration. A skilled person will know that ophthalmic compositions and their requirements are different from those that can be administered intravenously.

[0017] It is a known fact that liquid parenteral compositions of vancomycin hydrochloride have concerns due to limited stability in aqueous solution. Several attempts have been made to stabilize vancomycin by using various solubilizers, stabilizers and / or other excipients, as discussed above. OBJECTIVE OF THE INVENTION

[0018] It is an object of the invention to provide stable aqueous solutions of vancomycin or its pharmaceutically acceptable salt that are ready to administer intravenously to the patient, and those that can be diluted with a suitable diluent, prior to administration.

[0019] Another object of the invention is to provide a stable aqueous solution that contains vancomycin or its pharmaceutically acceptable salt as the sole active ingredient.

[0020] A further object of the invention is to provide a stable aqueous solution of vancomycin or its pharmaceutically acceptable salt that is stable over a long period of time at its storage temperature.

[0021] These and other objects and advantages of the invention will be apparent from the ensuing description.

[0022] SUMMARY OF THE INVENTION

[0023] The present disclosure provides aqueous parenteral composition of vancomycin hydrochloride that is stable over its shelf-life. The composition may be a ready-to-use solution composition of vancomycin that can be administered to the patient directly, or it may be a preconcentrate that is diluted with suitable diluents prior to administration to the patient.

[0024] Specifically, the present disclosure provides a stable aqueous pharmaceutical composition of vancomycin for parenteral use comprising:

[0025] (i) Vancomycin hydrochloride as the sole active ingredient;

[0026] (ii) at least one pharmaceutically acceptable buffer;

[0027] (iii) at least one pharmaceutically acceptable co-solvent;

[0028] (iv) a pharmaceutically acceptable stabilizing agent; wherein the composition when stored at about 2°C to about 8°C, has no less than 85% w / w of vancomycin B, at the end of its shelflife.

[0029] In one embodiment, the composition is a ready-to-use solution composition of vancomycin that can be administered to the patient directly. In a preferred embodiment, the composition is a preconcentrate that is diluted with suitable diluents prior to administration to the patient. In a preferred embodiment of the present disclosure, the pH of the pharmaceutical composition is about 3.5 to about 6.0.

[0030] In another preferred embodiment of the present disclosure, the pharmaceutically acceptable buffer is selected from the group comprising acetic acid, citric acid, tartaric acid and mixtures thereof.

[0031] In another embodiment of the present disclosure, the co-solvent is selected from glycerol or a combination of glycerol and propylene glycol.

[0032] In yet another embodiment of the present disclosure, the stabilising agent is glycine.

[0033] In a highly preferred embodiment, the pharmaceutical composition of the present disclosure comprises about 50 mg / ml of vancomycin hydrochloride, about 0.005% w / v to about 2% w / v of a buffer, about l%w / v to about 45%w / v of a co-solvent, about 0.01% w / v to about 1% w / v of a stabilising agent and sterile water for injection.

[0034] The pharmaceutical composition has a shelflife of at least 18 months and at the end of its shelf life has not more than 10% of the total impurities when stored at about 2°C to about 8°C.

[0035] DETAILED DESCRIPTION OF THE INVENTION

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0037] The terminology used in the description herein is for the purpose of describing particular embodiments only, and is not intended to be limiting of the disclosure.

[0038] Unless the context indicates otherwise, it is specifically intended that the various features of the disclosure described herein can be used in any combination.

[0039] Moreover, the present disclosure also contemplates that in some embodiments of the invention, any feature or combination of features set forth herein can be excluded or omitted. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference herein in their entirety for all purposes.

[0040] The term “comprising”, which is synonymous with “including”, “containing”, or “characterized by” herein defined as being inclusive or open-ended and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.

[0041] As used herein, “a,” “an,” or “the” can mean one or more than one.

[0042] Also, as used herein, “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).

[0043] Furthermore, the term “about,” as used herein when referring to a measurable value such as an amount of a compound, related compound, impurity or agent of this invention, dose, time, temperature, and the like, is meant to encompass variations of ±10% of the specified amount.

[0044] As used herein, the term “pharmaceutically acceptable” implies substances approved by a regulatory agency, such as the US Food and Drug Administration, listed in United States Pharmacopoeia (USP), and / or listed in the Inactive Ingredients Database of the USFDA, and are typically used in pharmaceutical preparations.

[0045] As used herein, the term “ready-to-administer” / “ready-to-use” means a liquid drug formulation that can be used directly, i.e., injected intravenously or diluted without the need for reconstitution.

[0046] As used herein, the term “ready-to-dilute” means a liquid drug formulation that can be diluted without the need for reconstitution.

[0047] The term “shelf life” refers to the amount of time the pharmaceutical composition may be stored without loss of potency and / or performance profile. In some embodiments of the present disclosure, shelflife refers to the amount of time the pharmaceutical composition may be stored without loss of about 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or 0.5% of the potency and / or performance of the active (vancomycin B), when stored at refrigerated conditions, i.e. about 2°C to about 8°C. The stable compositions provided herein are designed to have shelf life of at least 18 months. The vancomycin hydrochloride composition of the present disclosure is stable over its shelflife.

[0048] As used herein, and unless otherwise specified, the term “stable” refers to physical and chemical stability of the composition over the shelf-life of the composition. The United States Pharmacopoeia (USP) defines stability as “the ability of a product to retain its characteristics that it possessed during its manufacturing (physical, chemical, microbiological, therapeutic properties) within specified limits throughout its period of storage and use”. According to the ICH guidelines, pharmaceutical stability testing is defined as “systematic experiments conducted on pharmaceutical products to understand and provide evidence how the quality of a drug product varies under the influence of variety of environmental factors such as temperature, humidity and light, and to set re-test period for the drug, or a shelflife for the drug product and recommend good storage conditions”. In view of these, degradation products in a drug product are required to be evaluated and reported to the regulatory agencies. Further, USFDA requires parenteral formulations to be stable for a minimum period of 12 months (i.e. 48 weeks) at recommended storage condition, for approving the same for commercial use. For products to be commercially marketed in the US, there is an expectation that the products will comply to the standard throughout the shelf life. The composition of the present disclosure retains no less than 85% w / w of vancomycin 2°C to about 8°C at the end of its shelf life.

[0049] As used herein, “aqueous” means that the composition contains water.

[0050] As used herein, the term “parenteral” means administration by intravenous route of administration or by subcutaneous injection.

[0051] As used herein, the term “co-solvent” means an agent that is added to a primary solvent to increase the solubility of the vancomycin or its pharmaceutically acceptable salt. The primary solvent used in the present disclosure is typically sterile water for injection.

[0052] As used herein, the term “buffer” means an agent that helps maintain the pH of the composition.

[0053] The present disclosure provides aqueous parenteral composition of vancomycin hydrochloride that is stable over its shelf-life. The composition may be a ready-to-use solution composition of vancomycin that can be administered to the patient directly, or it may be a preconcentrate that is diluted with suitable diluents, prior to administration to the patient. Thus, in one embodiment, the present disclosure provides a ready-to-use solution composition of vancomycin containing 5mg / ml of vancomycin hydrochloride, and in another embodiment, it provides a ready-to-dilute solution composition of vancomycin containing 50mg / ml of vancomycin hydrochloride.

[0054] In an embodiment, the present disclosure provides stable aqueous parenteral composition of vancomycin hydrochloride wherein the amount of vancomycin (generally measured as vancomycin B) in the composition is not less than 85%w / w at the end of its shelf life, when stored at about 2°C to about 8°C , preferably not less than about 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% of vancomycin.

[0055] In another embodiment, of the present disclosure, composition at the end of its shelf life has not more than 10% of the total impurities when stored at about 2°C to about 8°C.

[0056] In an embodiment, the stable aqueous parenteral composition of the present disclosure includes vancomycin hydrochloride as the sole active ingredient, and contains one or more buffers, one or more cosolvent, glycine and water for injection. The composition has a typical pH in the range of about 3.5 to about 6.0.

[0057] In one embodiment of the present disclosure, buffers that can be used in the stable aqueous parenteral composition of the present disclosure include acetic acid, citric acid, tartaric acid and the like, and mixtures thereof. The buffer may be present in an amount ranging from about 0.005%w / v to about 2%w / v of the composition.

[0058] Suitable pH adjusting agents that can be used in the composition include Hydrochloric acid and / or Sodium Hydroxide to adjust the final pH to about 3.5 to about 6.0.

[0059] In another embodiment of the present disclosure, the cosolvents that may be used in the stable aqueous parenteral composition include one or more of propylene glycol and glycerol, and mixtures thereof, wherein the cosolvent is present in an amount ranging from about l%w / v to about 45%w / v of the composition. In a highly preferred embodiment, the cosolvent used is glycerol in an amount ranging from about 30%w / v to about 45% w / v. In an embodiment of the present disclosure, glycine is used as a stabilizer and may be present in an amount ranging from about 0.01%w / v to about l%w / v of the composition.

[0060] Solutions stabilized or manufactured according to the present disclosure are suitable for use in human or animal subjects by techniques known in the art, for example by sterilizing the solution by any suitable means, and packaging the solutions in sealed containers from which the solution can later be dispensed to the subject.

[0061] Typically, a sterile ready-to-use composition of the present invention can be obtained by (1) terminally sterilizing the composition in its final container, using moist heat sterilization, dry heat sterilization or radiation sterilization, or (2) by manufacturing and filling the composition in an aseptic manner, ensuring that the infrastructure used and the processes employed do not contribute to introduction of microbial contamination at any time. A person of skill in the art is aware of these methods and how these are to be carried out.

[0062] In preferred embodiments, the aqueous composition of the present invention is manufactured using aseptic processing and sterile filtration. In one embodiment, the ready-to-use composition is filtered using polyvinylidene fluoride (PVDF) sterile filter having pore size of 0.22p.

[0063] In another embodiment, the aqueous composition of the present disclosure is filled into a glass vial with rubber stopper for storage.

[0064] The present disclosure is further illustrated by reference to the following examples which is for illustrative purposes only, and does not limit the scope of the invention in any manner.

[0065] EXAMPLES

[0066] Example 1

[0067] Ready-to-use aqueous solutions of vancomycin were prepared as detailed in Table 1 below.

[0068] Table 1

[0069] The above formulations 1-6 were prepared by the following process. All the ingredients were dispensed as per the manufacturing formula, followed by transfer of 120% of water for injection into a stainless steel vessel and purged with nitrogen, until dissolved oxygen in the solution is below 2 ppm. About 80% as per batch quantity of nitrogen purged water for injection was transferred into a manufacturing vessel and to it was added required quantity of buffering agents (i.e. acetic acid, citric acid or tartaric acid), and stirred well to get a clear solution. The required quantity of glycine was then added into the above manufacturing vessel and stirred to obtain a clear solution. The co-solvent (propylene glycol or glycerol) was then added into the above manufacturing vessel and stirred until a homogenous solution is obtained. The pH of the bulk solution was adjusted to between 4.0 and 6.0 using diluted hydrochloric acid or sodium hydroxide solutions, followed by addition of vancomycin. The mixture was stirred until clear a solution was obtained, and the pH was adjusted to between 4.0 and 6.0 using diluted hydrochloric acid or sodium hydroxide solutions, if necessary. Finally, the volume was made up to 100% using the remaining quantity of nitrogen purged water for injection, followed by stirring. The final pH was then measured and recorded. A sample ofthe solutions was submitted for in-process analysis. Finally, the solution was filtered using 0.22p PVDF filter and filled into 100 m single port polypropylene bags, closed with a plastic port. The bags were packed in a triple laminated aluminum pouch, sealed and stored at 2-8°C.

[0070] Example 2

[0071] The ready-to-use aqueous solutions 1-6 of Example 1 were analysed, and the results are included in Table 2 below.

[0072] Table 2

[0073] The vancomycin B content was not less than 85% w / w at the end of the storage period, indicating a stable composition.

[0074] Example 3

[0075] A few more ready-to-use aqueous solutions of vancomycin hydrochloride were also prepared as per Table 3 below, by a process similar to that detailed in Example 1 above.

[0076] Table 3 Example 4

[0077] Ready-to-dilute aqueous solutions of vancomycin hydrochloride were prepared as detailed in

[0078] Table 4 below.

[0079] Table 4

[0080] The above formulations 13-19 were prepared by the following process. All the ingredients as per the manufacturing formula were dispensed. 120% of water for injection was transferred into a stainless-steel vessel and purged with nitrogen until dissolved oxygen in the water was below 2 ppm. About 80% as per batch quantity of the nitrogen purged water for injection was transferred into a manufacturing vessel, and to it was added the required quantity of buffering agents (i.e. acetic acid or tartaric acid) with stirring until a clear solution was obtained. The required quantity of glycine was added into the above manufacturing vessel and stirred well until a clear solution was formed. The required quantity of co-solvent (i.e. propylene glycol or glycerol) was then added into the above manufacturing vessel and stirred well to get a homogenous solution. The initial pH of the bulk solution thus obtained was measured and adjusted to between 4.0 and 6.0, using diluted solutions of Hydrochloric acid or Sodium hydroxide. Vancomycin was then added and stirred until a clear solution was obtained, followed by adjusting of the pH to between 4.0 and 6.0 using diluted Hydrochloric acid or Sodium hydroxide solutions, if necessary. Finally, the volume was made up to 100% using the remaining nitrogen purged water for injection and stirred well to obtain a clear homogenous solution. The final pH was measured and recorded, and submitted for in-process analysis. The bulk solution thus obtained was filtered using 0.22p PVDF filter and filled into 10 mL / 20 mm type-I glass vials with 10 mb fill. The vials were blanketed with nitrogen and stoppered with bromobutyl premium coated rubber stopper. The vials were stored at 2-8°C.

[0081] Example 5

[0082] The ready-to-dilute aqueous solutions of Example 4 were analysed, and the results are included in Table 5 below.

[0083] Table 5

[0084]

[0085] The composition was found to have not more than 6% of total impurities when stored for 1 month to 3 months at about 5°C. Further, the vancomycin B content was not less than 85% w / w.

[0086] EXAMPLE 6

[0087] Ready-to-dilute aqueous solutions of vancomycin hydrochloride were prepared as detailed in Table 6 below.

[0088] Table 6

[0089] The above formulations 20-22 were prepared by the following process. All the ingredients as per the manufacturing formula were dispensed. 120% of water for injection was transferred into a stainless-steel vessel and purged with nitrogen until dissolved oxygen in the water was below 2 ppm. About 30% to 80% as per batch quantity of the nitrogen purged water for injection was transferred into a manufacturing vessel, and to it was added the required quantity of buffering agent (i.e., acetic acid) with stirring until a clear solution was obtained. The required quantity of glycine was added into the above manufacturing vessel and stirred well until a clear solution was formed. The required quantity of co-solvent (i.e., glycerol) was then added into the above manufacturing vessel and stirred well to get a homogenous solution. The initial pH of the bulk solution thus obtained was measured and adjusted to around 4.0, using diluted solutions of Hydrochloric acid or Sodium hydroxide. Vancomycin was then added and stirred until a clear solution was obtained, followed by adjusting of the pH to around 4.0 using diluted Hydrochloric acid or Sodium hydroxide solutions, if necessary. Finally, the volume was made up to 100% using the remaining nitrogen purged water for injection and stirred well to obtain a clear homogenous solution. The final pH was measured and recorded, and submitted for in-process analysis. The bulk solution thus obtained was filtered using 0.22p PVDF filter and filled into 10 mL / 20 mm type-I glass vials with 10 m fill. The vials were blanketed with nitrogen and stoppered with bromobutyl premium coated rubber stopper. These vials were stored at 2-8°C.

[0090] EXAMPLE 7

[0091] The ready-to-dilute aqueous solutions of Example 6 were analysed, and the results are included in Table 2 below.

[0092] Note: NP - Not performed; ND - Not detected

[0093] The composition was found to have not more than 6% of total impurities when stored for 3-6 months at about 2°C to about 8°C. Further, the vancomycin B content was not less than 85% w / w.

Claims

We claim:

1. A stable aqueous pharmaceutical composition of vancomycin for parenteral use comprising:(i) vancomycin hydrochloride as the sole active ingredient;(ii) at least one pharmaceutically acceptable buffer;(iii) at least one pharmaceutically acceptable co-solvent;(iv) a pharmaceutically acceptable stabilizing agent; and(v) sterile water for injection wherein the composition when stored at about 2°C to about 8°C has no less than 85% w / w of vancomycin at the end of at least 6 months.

2. The pharmaceutical composition as claimed in claim 1, wherein the pH of the composition is about 3.5 to about 6.0.

3. The pharmaceutical composition as claimed in claim 1, wherein the pharmaceutically acceptable buffer is selected from the group comprising acetic acid, citric acid, tartaric acid and mixtures thereof.

4. The pharmaceutical composition as claimed in claim 1, wherein the pharmaceutically acceptable co-solvent is selected from glycerol, propylene glycol and mixtures thereof.

5. The pharmaceutical composition as claimed in claim 1, wherein the stabilising agent is glycine.

6. The pharmaceutical composition as claimed in claim 1 , wherein the composition comprises about 50 mg / ml of vancomycin hydrochloride; about 0.005% w / v to about 2% w / v of the buffer, about l%w / v to about 45%w / v of the co-solvent, about 0.01 % w / v to about 1% w / v of the stabilising agent and sterile water for injection.

7. The pharmaceutical composition as claimed in claim 1, wherein the composition has not more than 10% of the total impurities.

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