EP3544616A1

EP3544616A1 - Lyophilized pharmaceutical compositions of dalbavancin

Info

Publication number: EP3544616A1
Application number: EP17873284.8A
Authority: EP
Inventors: Mitesh Natavarlal Patel; Mafatlal Tribhovandas DAVE; Beena Pourusashap ANKLESARIA; Pranavkumar Jayesh Choksi
Original assignee: Gufic Biosciences Ltd
Current assignee: Gufic Biosciences Ltd
Priority date: 2016-11-23
Filing date: 2017-11-21
Publication date: 2019-10-02
Also published as: EP3544616A4; WO2018096556A1; RU2019119405A; RU2019119405A3

Abstract

A lyophilized pharmaceutical composition comprising: a) dalbavancin hydrochloride or its pharmaceutically acceptable salt; b) a pharmaceutically acceptable amount of amino acid as stabilizer) the ratio of dalvabancin to stabilizer is 1:0.8 to 1:1 by weight, d) said formulation has a pH in the range of 5.1-6 v) said formulation contains no more than about 1% MAG by weight after 3 Months at 40°C and 75 % RH.

Description

LYOPHILIZED PHARMACEUTICAL COMPOSITIONS OF

DALBAVANCIN"

Field of invention:

The present invention relates to lyophilized stable pharmaceutical compositions of Dalbavancin. More particularly, the present invention relates to pharmaceutical compositions comprising dalbavancin and an amino acid.

Background of the invention:

The emergence and spread of antimicrobial resistant organisms has made it increasingly difficult to treat serious Gram-positive infections and has dictated the need to develop new antimicrobial agents. Infections because of antimicrobial resistant pathogens have been associated with increased length of stay, health-care costs, morbidity and mortality. Studies have validated the association between increased mortality among critically ill patients and inappropriate antimicrobial selection, with resistance being the primary reason for inappropriate therapy.

There have been escalating rates of resistance over the last two decades, especially among the Gram-positive pathogens such as Staphylococcusspp., enterococci and streptococci. The efficacy of penicillinase resistant penicillins, vancomycin and teicoplanin, once the foundation for the treatment of multidrug resistant Gram- positive pathogens, is challenged daily.

The development of glycopeptide-resistant pathogens was initially identified in the late 1980s when vancomycin resistant enterococci (VRE) first emerged in hospitals. More recently in 1995, Staphylococcus aureus strains with increased vancomycin minimum inhibitory concentrations (MICs) were reported in the USA. Soon after, a heterogeneous vancomycin intermediate Staphylococcus aureus (VISA) strain was identified in Japan in 1996. In 2002, the first vancomycin resistant Staphylococcus aureus (VRSA) strain was reported in the USA. To date, there have been six VRSA isolates reported worldwide; all six have been reported in the USA, four of which have been reported in southeast Michigan. Vancomycin has long been considered the drug of choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Its modest efficacy, coupled with increasing reports of treatment failures as a result of elevated vancomycin MICs seen in a proportionally greater number of isolates, has made it increasingly important to find an alternative agent which is effective in the treatment of resistant Gram-positive infections.

Dalbavancin (formerly BI397) is a novel semisynthetic glycopeptide that was engineered to be an improved alternative to the naturally available glycopeptides, vancomycin and teicoplanin. Preliminary in vitro assays and animal models have demonstrated it to be more active than vancomycin or Teicoplanin against Gram- positive bacteria. It is anticipated to be approved by the Food and Drug Administration in the 1st quarter of 2007(International journal of clinical practice., May 2007,61, 5, 853-863).

Dalbavancin is a lipoglycopeptide synthesized from a fermentation product of Nonomuraea species.

Dalbavancin is a mixture of five closely related active homologs (AO, Al, BO, B l, and B2); the component BO is the major component of dalbavancin. The homologs share the same core structure and differ in the fatty acid side chain of the N- acylaminoglucuronic acid moiety (Rl) structure and/or the presence of an additional methyl group (R2) on the terminal amino group.

Substitution Patterns for Dalbavancin API Homologs

*Anhydrous free base

Molecular Formula Molecular

Dalbavancin Rl R2

Weight* C87H98N10O28C12

AO CH(CH3)2 H

HC1

C87H98N10O28C12

Al CH2CH2CH3 H

HC1

C88H100N10O28C12

BO CH2CH(CH3)2 H

HC1

C88H100N10O28C12

Bl CH2CH2CH2CH3 H

HC1

C89H102N10O28C12

B2 CH2CH(CH3)2 CI

HC1

The BO INN chemical name is: 5,31-dichloro-38-de(methoxycarbonyl)-7- demethyl-19-deoxy-56-O-[2-deoxy-2-[(10-methylundecanoyl)amino]-P-D- glucopyranuronosyl]-38-[[3-(dimethylamino)propyl] carbamoyl]-42-0-a-D- mannopyranosyl-15-N-methyl(ristomycin A aglycone) hydrochloride.

The chemical structure of Dalbavancin Hydrochloride is shown as formula I below:

Formulal Dalbavancin is marketed as lyophilized product for intravenous infusion by Durata Therapeutics US Limited under the trade name Dalvance® (Dalbavancin) for injection.

DALVANCE® (dalbavancin) for injection is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI), caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus) and Enterococcus faecalis (vancomycin susceptible strains).

Further, Dalbavancin is generally unstable to light, heat, humidity and hence it is necessary to develop a pharmaceutical composition for stabilizing the Dalbavancin compound and the salts thereof for parenteral administration.

Indian patent number 235498 disclose a dry pharmaceutical composition comprising: i) dalbavancin, ii) at least one stabilizer that is a sugar selected from the group consisting of mannitol, lactose, sucrose, sorbitol, glycerol, cellulose, trehalose, maltose and dextrose, iii) the ratio of dalvabancin to stabilizer is 2: 1 by weight, iv) said formulation has a pH in the range of 4-5, v) said formulation contains no more than about 5% MAG by weight after three months at 40°C.

MAG is defined as non-homologous dalbavancin compound lacking an acylglucoronamine moiety and is said to be a decomposition product of one or more of the dalbavancin components.

Currently available formulations in lyophilized vial contain lactose monohydrate and mannitol as stabilizing agent which does not provide desirable stability due to the sensitivity of Dalbavancin to environmental stress. Further, the formulations containing lactose are not suitable for patients with lactose intolerance.

Lactose intolerance is caused due to insufficient amount of enzyme lactase, which breaks lactose into glucose and galactose in the small intestines. The person who suffers from lactose intolerance cannot easily digest lactose.

Further, significant drawbacks exist to the use of sugars such as lactose in a pharmaceutical composition. Lactose has been attributed to transmission of certain stable viruses, prions or other infectious or pathogenic compounds, e.g., human transmissible spongiform encephalopathy (TSE). Consequently, there is increased regulatory scrutiny of pharmaceutical compositions containing lactose. Therefore, there is a need for a replacement for mammalian derived stabilizers such as lactose in the formulations.

In view of the instability associated with mammalian derived stabilizers of Dalbavancin in preparing the lyophilized product for parenteral administration as mentioned above, the present inventors felt a need in the art to provide a stable Dalbavancin injectable formulation with reduced impurities, good shelf life and further free from sugars, specifically, lactose to avoid lactose intolerance.

Therefore, it is an object of the present invention to provide stable Dalbavancin injectable formulation having no more than about 1% MAG by weight for a storage period of over 3 months at 40°C and 75 % RH and a replacement for mammalian derived stabilizers such as lactose for the preparation of pharmaceutical compositions containing Dalbavancin.

Summary of the invention:

While screening for suitable agents for stabilizing the formulation, the inventors have unexpectedly found that stabilized pharmaceutical formulation of Dalbavancin can be prepared for parenteral administration, without employing sugars, however using a suitable stabilizing agent.

Accordingly, the present invention provides pre-lyophilized pharmaceutical formulation comprising Dalbavancin or pharmaceutically acceptable salt thereof along with a suitable stabilizing agent in an aqueous vehicle, wherein, the formulation is free from sugars.

In a preferred aspect, pharmaceutically acceptable salt of Dalbavancin is Dalbavancin Hydrochloride.

The Dalbavancin Hydrochloride is stabilized by adding an amino acid as a stabilizing agent selected from the group consisting of L-proline, L-arginine, L- serine,etc. in aqueous vehicle to obtain pre-lyophilized formulation.

In one preferred aspect, the stabilizing agent is L-proline.

In another aspect, the pre-lyophilized pharmaceutical formulation of Dalbavancin Hydrochloride and stabilizing agent is lyophilized and provided as a drug concentrate, suitable for parenteral administration.

According to the invention, the lyophilized formulation comprises an effective amount of stabilizer in the range of lOOmg to 1000 mg.

The pH of the formulation is maintained in the range of 5.1 to 6 using alkalizing agent such as sodium hydroxide solution.

In another aspect, the present invention provides a method for stabilization of Dalbavancin Hydrochloride in an aqueous solution which comprises combining Dalbavancin Hydrochloride in an aqueous vehicle with an amino acid as a stabilizing agent selected from the group consisting of L-proline, L-arginine, L- serine etc. One preferred amino acid is L-proline.

Detailed description of the invention:

The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be fully understood and appreciated.

Dalbavancin Hydrochloride is generally unstable to heat, humidity, acid, and the like, it is therefore necessary to develop a stable pharmaceutical composition for parenteral administration or for intravenous infusion.

Accordingly, the present invention provides stable pharmaceutically acceptable composition/formulation for parenteral administration or intravenous infusion comprising Dalbavancin Hydrochloride as the active and an amino acid as a suitable stabilizer by maintaining appropriate pH of the formulation.

In an embodiment, the present invention provides pre-lyophilized pharmaceutical composition comprising Dalbavancin Hydrochloride; a pharmaceutically acceptable amino acid as stabilizing agent selected from the group consisting of L- proline, L-arginine and L-serine in an aqueous vehicle and an alkalizing agent such as sodium hydroxide solution wherein, pH of said composition is in the range of 5.1 to 6.0 and wherein, the pre-lyophilized composition is devoid of sugars. The aqueous vehicle according to the invention is water for injection.

Dalbavancin Hydrochloride is present in the composition in an amount ranging from lOOmg to 1000 mg/vial; more preferably 500mg to 1000 mg/vial.

Dalbavancin Hydrochloride is stabilized using a suitable stabilizing agent where Dalbavancin Hydrochloride can be maintained in a dissolved state in the aqueous solution thereby preventing crystallization or crystalline growth of Dalbavancin Hydrochloride. The stabilizing agent is selected from the group consisting of an amino acid selected from the group consisting of L-proline, L-arginine, L-serine etc. One preferred stabilizing agent is L-proline.

In a preferred embodiment, the pre-lyophilized pharmaceutical composition comprises Dalbavancin Hydrochloride in an amount ranging from lOOmg to 1000 mg/vial; an effective amount of L-prolinein the range of lOOmg to lOOOmg as a stabilizing agent in aqueous vehicle and 0.1N sodium hydroxide solution as alkalizing agent for pH adjustment. The pre-lyophilized composition thus provided in aqueous vehicle is filtered to remove particulate matter, filled into vials and subjected to lyophilization cycle to obtain lyophilized composition.

Since, Dalbavancin Hydrochloride is not stable to humidity and temperature it was necessary to reduce the water content to the desirable extent to obtain the lyophilized product with reduced total impurities and increased stability. Accordingly, in an embodiment, the present invention provides lyophilized composition of Dalbavancin Hydrochloride with water content less than 1.5%w/w, preferably in the range of 0.5 to 1.5%w/w; most preferably the water content is in an amount of about 1.0%w/w.

The present inventors have observed during experimentation that there is an increase in total impurities on storage of the lyophilized composition of Dalbavancin at 70°C for 7 days and further conducted stability studies on various Dalbavancin compositions so as to provide a stable composition having MAG impurity levels not more than 1%.

In accordance with the same, the lyophilized formulation of dalbavancin of the present invention (composition 2) is subjected to accelerated degradation studies at high temperature of 70°C for 7 days and compared the same with marketed formulation (composition 1) and presented the data in table 1, wherein the dalbavancin formulation of the present invention (Composition 2) exhibits more stability over the marketed formulation (composition 1) indicating the suitability of the amino acid over the lactose present in the marketed formulation.

In another embodiment, the invention provides accelerated degradation studies of the present composition having dalbavancin and amino acid in variable ratio of 1 : 0.6 (composition 3) and l : l(composition 4) at 70 °C for 7 days to assess the minimum amount of the stabilizer required to provide the desired stability. The results are tabulated under table 2. According to the results of table 2, composition 4 exhibits better stability when compared to composition 3.

In yet another embodiment, the lyophilized formulation of dalbavancin of the present invention is subjected to accelerated degradation studies at 40°C with relative humidity of 75% moisture for three months and compared the same with marketed formulation and presented the data in table 3, wherein the dalbavancin formulation of the present invention (Composition 6 having dalbavancin to L- proline in a ratio of 1 :0.8) exhibits more stability over the marketed formulation (composition 5).

Accordingly, the present invention provides stable, lyophilized pharmaceutical composition for parenteral administration, which is free from sugars, comprising; i) dalbavancin hydrochloride or its pharmaceutically acceptable salt;

ii) a pharmaceutically acceptable amount of amino acid as stabilizer; and iii) an alkalizing agent,

wherein, the composition has a pH in the range of 5.1-6.0 and whereby said composition contains no more than aboutl% MAG by weight after 3 Months at 40°C and 75% RH.

The ratio of dalvabancin base to stabilizer is preferably in a ratio of 1 :0.8 to 1 : 1.

The amino acid as a stabilizing agent is selected from the group consisting of L- proline, L-arginine, L-serine, etc. In a preferred embodiment, the stabilizing agent is L-proline used in an amount of 100 to lOOOmg.

In another embodiment, the present invention provides stable, lyophilized pharmaceutical composition for parenteral administration, which is free from sugars, comprising;

i) Dalbavancin Hydrochloride equivalent to anhydrous Dalbavancinin in an amount of 100 mg to 1000 mg/vial;

ii) lOOmg to lOOOmg of L-proline in aqueous vehicle as a stabilizing agent; iii) Sodium Hydroxide solution as alkalizing agent to regulate pH of said composition in the range of 5.1 -6.0.

In one preferred embodiment, the lyophilized pharmaceutical composition for parenteral administration comprises Dalbavancin Hydrochloride equivalent to anhydrous Dalbavancinin in an amount of 500 mg/vial and the L-proline in an amount of 400 mg.

In an alternate embodiment, the lyophilized pharmaceutical composition for parenteral administration comprises Dalbavancin Hydrochloride equivalent to anhydrous Dalbavancinin in an amount of 500 mg/vial and the L-proline in an amount of 500 mg.

According to another embodiment, the invention provides lyophilzation process which involves cooling of pre-lyophilized pharmaceutical composition comprising dalbavancin at suitable temperature not less than -45°C, raising temperature to 0°C at suitable pressure of 500 mtorr to 100 mtorr in 30 hours, then at 50mtorr, further raising temperature to +30°C in 20hrs, to obtain lyophilized composition. The secondary drying of the composition is carried at a temperature in the range of +25 to +35°C for 5 hours to obtain lyophilized composition comprising the water content less than 1.5 %w/w. The lyophilized composition of Dalbavancin containing L-proline in aqueous vehicle as a stabilizing agent with water content less than 1.5 %w/w according to the present invention have total impurities less than the prior art formulations as illustrated in tables 1 and 3 below.

Such compositions after lyophilization is chemically and physically stable over an extended period of time and is suitable for intended pharmaceutical use after reconstitution with suitable vehicle/diluents such as water for injection or 5% dextrose injection.

The lyophilized Dalbavancin Hydrochloride composition provided in accordance with this invention when reconstituted with 25 ml of suitable vehicle contains final drug concentrate of 20 mg/ml and subsequently diluted with 5% Dextrose Injection, to a final concentration of 1 mg/mL to 5 mg/mL.

In another embodiment, the invention provides a process for preparation of lyophilized pharmaceutical composition of the invention which comprises a) providing pre-lyophilized composition consisting of Dalbavancin Hydrochloride dissolved in aqueous vehicle containing stabilizing agent and alkalizing agent and b) lyophilizing the composition to obtain lyophilized pharmaceutical composition with water content less than 1.5%.

The lyophilized composition comprising Dalbavancin Hydrochloride may be diluted with suitable diluents before administration as IV injection. The final concentration of solution may be reduced further to desired level using 5% Dextrose infusion prior to administration to a patient.

The pharmaceutical compositions of the present invention are administered to a patient according to a dosing regimen. It should be understood that the specific dosing regimen for any particular patient will depend on a variety of factors, including age, body weight, general health, sex, diet, time of administration, specific disease being treated, and the severity of the condition among other factors and the judgment of the treating physician.

In conclusion, the present invention provides lyophilized pharmaceutical composition comprising Dalbavancin which is free from sugars without compromising on the stability of drug and its solution before Lyophilisation and as lyophilized composition with less than 1.5%w/w water content, with reduced amount of total impurities which is stable for the entire period of the shelf life. The use of amino acid, viz., L-proline as stabilizing agent provides increased stability to Dalbavancin and eliminates significant drawbacks of the use of mammalian derived stabilizer such as lactose and thus the parenteral formulation of the present invention is suitable for administration to lactose sensitive patients as well as to normal patients providing the desired therapeutic activity with no side effects.

Other features and embodiments of the invention will become apparent by the following examples which are given for illustration of the invention rather than limiting its intended scope. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art.

Experiments:

Composition: 1

5.7 Gm Dalbavancin hydrochloride equivalent to 5.0 gm Dalbavancin (active) was added in water for injection having temperature below 30 °C and dissolved it then added 1.29 gm of Lactose monohydrate and 1.29 gm Mannitol into it and stirred for some time to get clear solution. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 4.5. Filtered the solution and the resulting solution was loaded into 10 vials (25 ml vial) with each containing 10 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at70°C, and the residue of Dalbavancin was tested after seven days and the results are provided in below table 1.

Composition: 2

5.7 Gm Dalbavancin hydrochloride equivalent to 5.0 gm Dalbavancin (active) was added to an aqueous solution containing 4 gm of L-Proline and stirred for some time to get clear solution. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 5.5. Filtered the solution and the resulting solution was loaded into 10 vials (25 ml vial) with each containing 10 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at70°C, and the residue of Dalbavancin was tested after seven days and the results are provided in below table 1.

Accelerated Study Results:

Table 1

Vial kept at 70 °C for 7 days parameters Composition- 1 Composition-2

MAG impurity 2.91% 1.60 % Single max impurity 0.66% 0.22 %

Total impurities 4.31% 2.81 %

Composition: 3

5.7 Gm Dalbavancin hydrochloride equivalent to 5.0 gm Dalbavancin (active) was added to an aqueous solution containing 3 gm of L-Proline and stirred for some time to get clear solution having temperature below 10 °C. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 5.3. Filtered the solution and the resulting solution was loaded into 10 vials (25 ml vial) with each containing 11 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at70°C, and the residue of Dalbavancin was tested after seven days and the results are provided in below table 2.

Composition: 4

5.7 GmDalbavancin hydrochloride equivalent to 5.0 gmDalbavancin (active) was added to an aqueous solution containing 5 gm of L-Proline and stirred for some time to get clear solution having temperature below 10 °C. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 5.3.Filtered the solution and the resulting solution was loaded into 10 vials (25 ml vial) with each containing 11 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at70°C, and the residue of Dalbavancin was tested after seven days and the results are provided in below table 2.

Accelerated Study results

Table 2

Composition: 5

5.7 Gm Dalbavancin hydrochloride equivalent to 5.0 gm Dalbavancin (active) was added in water for injection having temperature below 30 °C and dissolves it then added 1.29gm of Lactose monohydrate and 1.29 gm Mannitol into it and stirred for some time to get clear solution. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 4.5 and made up the volume. Filtered the solution and the resulting solution was loaded into 10 vials (30 ml vial) with each containing 10 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at 40°C and 75% RH, and the residue of Dalbavancin was tested after 3 Months and the results are provided in below table 3. Sr.No. Ingredients Qty./Vial

1 DalbavancinHCl equivalent to anhydrous Dalbavancin 500 mg

2 Lactose monohydrate 129 mg

3 Mannitol 129 mg

4 Sodium hydroxide for pH adjustment Q.S.

5 Water for injection Q.S.

Composition: 6

5.7 Gm Dalbavancin hydrochloride equivalent to 5.0 gm Dalbavancin (active) was added to an aqueous solution containing 4 gm of L-Proline and stirred for some time to get clear solution having temperature below 10 °C. Adjusted pH with 1.0 N Sodium Hydroxide solution to about 5.3 and make up the volume .Filtered the solution and the resulting solution was loaded into 10 vials (30 ml vial) with each containing 11 ml solution. The solution in each vial was lyophilized using freeze dryer according to conventional method, thereby obtaining the lyophilized compositions each comprising 500 mg of Dalbavancin. The resulting lyophilized preparation was stored at 40°C and 75 % RH, and the residue of Dalbavancin was tested after 3 Months and the results are provided in below table 3.

Sr.No. Ingredients Qty./Vial

1 DalbavancinHCl equivalent to anhydrous Dalbavancin 500 mg

2 L-proline 400 mg

3 Sodium hydroxide for pH adjustment Q.S.

4 Water for injection Q.S. Accelerated Study results:

Table 3

Industrial Advantages:

1. The lyophilized pharmaceutical composition comprising Dalbavancin Hydrochloride which is free from sugar is provided herewith without compromising stability of drug and its solution before Lyophilisation has a pH between 5.1 to 6.0.

2. The formulation is stable for the entire period of the shelf life.

3. The stability of the freeze dried composition is more stable than the prior art formulation.

Claims

We claim:

1. A stable lyophilized pharmaceutical composition comprising:

i) dalbavancin hydrochloride or its pharmaceutically acceptable salt;

ii) a pharmaceutically acceptable amount of amino acid as stabilizer; and iii) an alkalizing agent to regulate pH;

wherein, said composition has a pH in the range of 5.1-6.0 and whereby said composition contains no more than about 1% MAG by weight after 3 Months at 40°C and 75 % RH.

2. The lyophilized pharmaceutical composition as claimed in claim 1, wherein the Dalbavancin Hydrochloride is in an amount of 100 mg to 1000 mg.

3. The lyophilized pharmaceutical composition as claimed in claim 1, wherein the amino acid is selected from the group consisting of L-proline, L-arginine and L-serine.

4. The lyophilized pharmaceutical composition as claimed in claim 3, wherein the amino acid is L-proline.

5. The lyophilized pharmaceutical composition as claimed in claim 4, wherein the L-Proline is in an amount of 100 mg to 1000 mg.

6. The lyophilized pharmaceutical composition as claimed in claim 1, wherein the ratio of dalvabancin base to L-Proline is in the range of 1 :0.8 to 1 : 1.

7. . The lyophilized pharmaceutical composition as claimed in claim 1, wherein the alkalizing agent is sodium hydroxide solution.

8. The lyophilized pharmaceutical composition as claimed in claim 1 comprises; i) Dalbavancin Hydrochloride equivalent to anhydrous Dalbavancinin an amount of 500 mg/vial;

ii) 400mg of L-proline in aqueous vehicle as a stabilizing agent;

iii) Sodium Hydroxide solution as alkalizing agent to regulate pH of said composition in the range of 5.1-6.0.

9. The lyophilized pharmaceutical composition as claimed in claim 1 comprises; i) Dalbavancin Hydrochloride equivalent to anhydrous Dalbavancinin an amount of 500 mg/vial;

ii) 500mg of L-proline in aqueous vehicle as a stabilizing agent;

10. A process for preparation of the lyophilized pharmaceutical composition as claimed in claim 1, comprises:

a) Providing pre-lyophilized composition consisting of dalbavancin hydrochloride dissolved in aqueous vehicle containing stabilizing agent and alkalizing agent and

b) lyophilizing the composition to obtain freeze dried pharmaceutical composition with water content less than 1.5%.