Indian Patents. 234931:NOVEL TOPICAL COMPOSITIONS OF SODIUM FUSIDATE

Title of Invention	NOVEL TOPICAL COMPOSITIONS OF SODIUM FUSIDATE
Abstract	Disclosed herein are stable powdered compositions for topical application, comprising therapeutically effective amount of sodium fusidate in association with pharmaceutically acceptable powdered vehicle.

Full Text	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: "Novel topical compositions of sodium fusidate" 2. APPLICANT (S) (a) NAME: Salgaocar, Dilip Ramcrisna (b)NATIONALITY: Indian (c) ADDRESS: Sharvani, Pedem, Mapusa, Goa - 403507, India. 3. PREAMBLE TO THE DESCRIPTION The following specification particularly describes the invention and the manner in which it is to be performed: Technical Field of the invention: The present invention relates to novel dry powder compositions of sodium fusidate for topical application for treatment of infections due to staphylococci and other strains resistant to antibiotics. Background and Prior Art: Fusidic acid and sodium fusidate are mainly used in treatment of staphylococcal infections in single ingredient or multiple active ingredient dosage forms. In recent years, sodium fusidate has been increasingly used as an anti-infective. It is also used as an agent to treat strains resistant to antibiotics. Sodium fusidate is conventionally available for local treatment of skin infections at 2% concentration as an ointment, cream or gel. US Patent 4,323,558 describes sodium fusidate alone or in combination with tienes (triethylenetetramine) in form of gel, ointment or lotion in 1% concentration for treatment of inflammation. A series of patents including US Patent 6,699,505 are disclosed on complexing of sodium fusidate (among others) with Cyclodextrins. However, there are no topical dosage forms of sodium fusidate reported in prior art or marketed in dry powder form, which has substantial therapeutic benefits as well as patient convenience in local treatment of skin infections. It is clear from the above text, that a pharmaceutically stable and biologically equivalent formulation of sodium fusidate for topical application is required for a large section of patient population. However, no such stable formulation of sodium fusidate for local administration is available for convenient delivery. The present invention of powder dosage form for topical application fulfils this unmet need. The major challenges of formulating sodium fusidate powder include a) smoothness, non 2 tacky nature, b) maintaining the optimum flow of the drug, c) ensuring long term stability, and d) ensuring bioequivalence. Summary of the invention: Sodium fusidate is formulated herein into a dry powder composition for use in topical treatment of skin infections, especially those that are resistant to antibiotics. The present invention discloses stable pharmaceutical compositions in powder form for topical application comprises therapeutically effective amount of 2-3% of sodium fusidate in association with pharmaceutically acceptable powdered vehicle-Detailed Description: The present invention is directed to a solid pharmaceutical composition for topical application to a subject in need thereof, which comprises of therapeutically effective amount of sodium fusidate in association with a pharmaceutically acceptable solid carrier. In a preferred embodiment, the present invention is directed to a solid formulation of sodium fusidate, wherein the formulation comprises of therapeutically effective amount of sodium fusidate in a solid carrier, in association with pharmaceutical acceptable powdered vehicle which is free sprinkling and uniform with ensured long term chemical stability, and established pharmacokinetic equivalency. The said vehicle comprises of one or more excipients selected from colloidal silicon dioxide, purified talc, purified starch and sodium starch glycollate, or combination thereof. It is most preferred that it contains all these components. The said pharmaceutical composition may optionally contain a buffering agent. One such embodiment containing sodium fusidate and other carefully selected excipients shows: a) good physical stability of the sodium fusidate and other excipients upon storage under normal and stress conditions, b) is free flowing by virtue of the composition of the formulation and c) excellent chemical stability upon storage under normal and stress condition; maintains more than 95% of its initial content when exposed to 45°C for three 3 months or more, 98% of its initial content when exposed to 40°C/75% relative humidity for three months or more, and more than 98% of its initial content when stored at room temperature for two years or more. Such embodiment containing sodium fusidate formulated as solid dosage form for topical application is useful for treating infections due to staphylococci, especially strains resistant to other antibiotics, in a subject or clinical situation where ointments or creams are not feasible to be used. Such embodiment is especially useful in a patient population consisting of geriatric, paediatric, bed-ridden, and/or in-tubated patients, and others who experience difficulty in swallowing oral dosage forms or clinically cannot be subjected to application of ointment or cream/gel forms or cannot accept local application of ointments or creams. The solid formulation has been shown to be chemically compatible with many other common applications and can be applied with ease. Other major attributes of such embodiment of sodium fusidate topical formulation in powder form are its proven bioavailability with a commercially available leading brand of creams and ointment dosage forms. One such embodiment of sodium fusidate powder was investigated in a relative bioavailability study in which comparison with a leading brand formulation was performed. Proof of such bioequivalence of the subject embodiment is extremely important in clinical as well as pharmacy practice since switchover from topical gel cream/ointment to topical powder formulation for local application can occur automatically without the need for physician's approval. In a more preferred embodiment, the formulation of the present invention contains at least one or more of the following components: 2-3% by weight of sodium fusidate, about 5% to about 40% by weight of silicon dioxide, about 40% to about 80% by weight of purified talc, about 5% to about 20% by weight of starch, about 5% to about 20% by weight of sodium starch glycollate. 4 In another preferred embodiment, the formulation comprises a therapeutically effective amount of 2-3% by weight of Sodium fusidate in a carrier that comprises of about 40% to about 80% by weight of starch about 5% to about 20% by weight of purified talc, about 5% to about 20% by weight of sodium starch glycollate about 5% to about 20% by weight of silicon dioxide. Yet in another preferred embodiment, the formulation comprises a therapeutically effective amount of 2-3% by weight of sodium fusidate, in a carrier that comprises about 20% to about 50% by weight of purified talc, about 5% to about 20% by weight of colloidal silicon dioxide, about 20% to about 50% by weight of purified starch, about 5% to about 20% by weight of sodium starch glycollate. The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention. Example 1: In a suitable manufacturing container, 782gms of purified talc # 60 was taken. To this 23gms of sodium fusidate # 200 was added in geometric proportions while mixing.. To this mixture 60gms of silicone dioxide # 60, 75 gms of starch 60# and 60 gms of Sodium Starch Glycollate # 60 were added one after another while mixing in a ribbon blender. Final mixing was done for 20 minutes. Example 2: In a suitable manufacturing container, 767gms of starch # 60 was taken.. To this 23gms of sodium fusidate # 200 was added in geometric proportions, while mixing. To this mixture 50 gms of Silicone Dioxide # 60, 60gms of Sodium starch glycollate # 60 and 100 gms of Purified Talc # 60 were added one followed by the other. Final mixing was done for 20 minutes. 5 Example 3: In a suitable manufacturing container, 438.5 gms of starch # 60 and 438.5 gms of Purified Talc # 60 were mixed, 50gm of sodium starch glycollate # 60 and 50gms of Silicon Dioxide 60# were mixed with 23 gms of Sodium Fusidate # 200 in geometric proportions in a blender for 45 minutes. It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative examples and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof, and it is therefore desired that the present embodiments and examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. 6 We Claim 1. A stable pharmaceutical composition in powder form for topical application comprising therapeutically effective amount of sodium fusidate in association with pharmaceutically acceptable powdered vehicle. 2. The powder composition as claimed in claim 1, wherein said therapeutically effective amount of sodium fusidate is 2-3% by weight. 3. The powder composition as claimed in claim 1, wherein said pharmaceutically acceptable powdered vehicle comprises of one or more excipients selected from colloidal silicon dioxide, purified talc, purified starch, sodium starch glycollate, and buffering agent or combination thereof. 4. The powder composition as claimed in claims 1 and 3, wherein said colloidal silicon dioxide is in the range of 5-40 % by weight. 5. The powder composition as claimed in claims 1 and 3, wherein said purified talc is in the range of 5-80% by weight. 6. The powder composition as claimed in claims 1 and 3, wherein said purified starch is in the range of 5-80% by weight. 7. The powder composition as claimed in claims 1 and 3, wherein said sodium starch glycollate is in the range of 5-20% by weight. 8. The powder composition as claimed in any of the preceding claims, wherein said composition optionally comprises buffering agent. 9. Topical application of sodium fusidate in powder form as substantially exemplified in examples 1 to 3 useful for treating infections due to staphylococci, especially strains resistant to other antibiotics. Dr. Gopakumar G. Nair Agent for the Applicant 7 Dated this 21st day of June 2006 ABSTRACT: Disclosed herein are stable powdered compositions for topical application, comprising therapeutically effective amount of sodium fusidate in association with pharmaceutically acceptable powdered vehicle. 21 JUN 2006 8

Full Text

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:
"Novel topical compositions of sodium fusidate"
2. APPLICANT (S)
(a) NAME: Salgaocar, Dilip Ramcrisna
(b)NATIONALITY: Indian
(c) ADDRESS: Sharvani, Pedem, Mapusa, Goa - 403507, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed:

Technical Field of the invention:
The present invention relates to novel dry powder compositions of sodium fusidate for topical application for treatment of infections due to staphylococci and other strains resistant to antibiotics.
Background and Prior Art:
Fusidic acid and sodium fusidate are mainly used in treatment of staphylococcal infections in single ingredient or multiple active ingredient dosage forms.
In recent years, sodium fusidate has been increasingly used as an anti-infective. It is also used as an agent to treat strains resistant to antibiotics.
Sodium fusidate is conventionally available for local treatment of skin infections at 2% concentration as an ointment, cream or gel. US Patent 4,323,558 describes sodium fusidate alone or in combination with tienes (triethylenetetramine) in form of gel, ointment or lotion in 1% concentration for treatment of inflammation. A series of patents including US Patent 6,699,505 are disclosed on complexing of sodium fusidate (among others) with Cyclodextrins.
However, there are no topical dosage forms of sodium fusidate reported in prior art or marketed in dry powder form, which has substantial therapeutic benefits as well as patient convenience in local treatment of skin infections.
It is clear from the above text, that a pharmaceutically stable and biologically equivalent formulation of sodium fusidate for topical application is required for a large section of patient population. However, no such stable formulation of sodium fusidate for local administration is available for convenient delivery. The present invention of powder dosage form for topical application fulfils this unmet need.
The major challenges of formulating sodium fusidate powder include a) smoothness, non
2

tacky nature, b) maintaining the optimum flow of the drug, c) ensuring long term stability, and d) ensuring bioequivalence.
Summary of the invention:
Sodium fusidate is formulated herein into a dry powder composition for use in topical treatment of skin infections, especially those that are resistant to antibiotics. The present invention discloses stable pharmaceutical compositions in powder form for topical application comprises therapeutically effective amount of 2-3% of sodium fusidate in association with pharmaceutically acceptable powdered vehicle-Detailed Description:
The present invention is directed to a solid pharmaceutical composition for topical application to a subject in need thereof, which comprises of therapeutically effective amount of sodium fusidate in association with a pharmaceutically acceptable solid carrier. In a preferred embodiment, the present invention is directed to a solid formulation of sodium fusidate, wherein the formulation comprises of therapeutically effective amount of sodium fusidate in a solid carrier, in association with pharmaceutical acceptable powdered vehicle which is free sprinkling and uniform with ensured long term chemical stability, and established pharmacokinetic equivalency. The said vehicle comprises of one or more excipients selected from colloidal silicon dioxide, purified talc, purified starch and sodium starch glycollate, or combination thereof. It is most preferred that it contains all these components. The said pharmaceutical composition may optionally contain a buffering agent.
One such embodiment containing sodium fusidate and other carefully selected excipients shows: a) good physical stability of the sodium fusidate and other excipients upon storage under normal and stress conditions, b) is free flowing by virtue of the composition of the formulation and c) excellent chemical stability upon storage under normal and stress condition; maintains more than 95% of its initial content when exposed to 45°C for three
3

months or more, 98% of its initial content when exposed to 40°C/75% relative humidity for three months or more, and more than 98% of its initial content when stored at room temperature for two years or more.
Such embodiment containing sodium fusidate formulated as solid dosage form for topical application is useful for treating infections due to staphylococci, especially strains resistant to other antibiotics, in a subject or clinical situation where ointments or creams are not feasible to be used.
Such embodiment is especially useful in a patient population consisting of geriatric, paediatric, bed-ridden, and/or in-tubated patients, and others who experience difficulty in swallowing oral dosage forms or clinically cannot be subjected to application of ointment or cream/gel forms or cannot accept local application of ointments or creams. The solid formulation has been shown to be chemically compatible with many other common applications and can be applied with ease.
Other major attributes of such embodiment of sodium fusidate topical formulation in powder form are its proven bioavailability with a commercially available leading brand of creams and ointment dosage forms. One such embodiment of sodium fusidate powder was investigated in a relative bioavailability study in which comparison with a leading brand formulation was performed. Proof of such bioequivalence of the subject embodiment is extremely important in clinical as well as pharmacy practice since switchover from topical gel cream/ointment to topical powder formulation for local application can occur automatically without the need for physician's approval.
In a more preferred embodiment, the formulation of the present invention contains at least one or more of the following components: 2-3% by weight of sodium fusidate, about 5% to about 40% by weight of silicon dioxide, about 40% to about 80% by weight of purified talc, about 5% to about 20% by weight of starch, about 5% to about 20% by weight of sodium starch glycollate.
4

In another preferred embodiment, the formulation comprises a therapeutically effective amount of 2-3% by weight of Sodium fusidate in a carrier that comprises of about 40% to about 80% by weight of starch about 5% to about 20% by weight of purified talc, about 5% to about 20% by weight of sodium starch glycollate about 5% to about 20% by weight of silicon dioxide.
Yet in another preferred embodiment, the formulation comprises a therapeutically effective amount of 2-3% by weight of sodium fusidate, in a carrier that comprises about 20% to about 50% by weight of purified talc, about 5% to about 20% by weight of colloidal silicon dioxide, about 20% to about 50% by weight of purified starch, about 5% to about 20% by weight of sodium starch glycollate.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
Example 1:
In a suitable manufacturing container, 782gms of purified talc # 60 was taken. To this 23gms of sodium fusidate # 200 was added in geometric proportions while mixing.. To this mixture 60gms of silicone dioxide # 60, 75 gms of starch 60# and 60 gms of Sodium Starch Glycollate # 60 were added one after another while mixing in a ribbon blender. Final mixing was done for 20 minutes.
Example 2:
In a suitable manufacturing container, 767gms of starch # 60 was taken.. To this 23gms of sodium fusidate # 200 was added in geometric proportions, while mixing. To this mixture 50 gms of Silicone Dioxide # 60, 60gms of Sodium starch glycollate # 60 and 100 gms of Purified Talc # 60 were added one followed by the other. Final mixing was done for 20 minutes.
5

Example 3:
In a suitable manufacturing container, 438.5 gms of starch # 60 and 438.5 gms of Purified Talc # 60 were mixed, 50gm of sodium starch glycollate # 60 and 50gms of Silicon Dioxide 60# were mixed with 23 gms of Sodium Fusidate # 200 in geometric proportions in a blender for 45 minutes.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative examples and that the present invention may be embodied in other specific forms without departing from the essential attributes thereof, and it is therefore desired that the present embodiments and examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
6
We Claim
1. A stable pharmaceutical composition in powder form for topical application comprising therapeutically effective amount of sodium fusidate in association with pharmaceutically acceptable powdered vehicle.
2. The powder composition as claimed in claim 1, wherein said therapeutically effective amount of sodium fusidate is 2-3% by weight.
3. The powder composition as claimed in claim 1, wherein said pharmaceutically acceptable powdered vehicle comprises of one or more excipients selected from colloidal silicon dioxide, purified talc, purified starch, sodium starch glycollate, and buffering agent or combination thereof.
4. The powder composition as claimed in claims 1 and 3, wherein said colloidal silicon dioxide is in the range of 5-40 % by weight.
5. The powder composition as claimed in claims 1 and 3, wherein said purified talc is in the range of 5-80% by weight.
6. The powder composition as claimed in claims 1 and 3, wherein said purified starch is in the range of 5-80% by weight.
7. The powder composition as claimed in claims 1 and 3, wherein said sodium starch glycollate is in the range of 5-20% by weight.
8. The powder composition as claimed in any of the preceding claims, wherein said composition optionally comprises buffering agent.
9. Topical application of sodium fusidate in powder form as substantially exemplified in examples 1 to 3 useful for treating infections due to staphylococci, especially strains resistant to other antibiotics.

Dr. Gopakumar G. Nair Agent for the Applicant
7
Dated this 21st day of June 2006

ABSTRACT:
Disclosed herein are stable powdered compositions for topical application, comprising therapeutically effective amount of sodium fusidate in association with pharmaceutically acceptable powdered vehicle.

21 JUN 2006
8

Documents:

1622-MUM-2005-ABSTRACT(21-6-2006).pdf

1622-mum-2005-abstract.doc

1622-mum-2005-abstract.pdf

1622-MUM-2005-CLAIMS(3-10-2008).pdf

1622-mum-2005-claims.doc

1622-mum-2005-claims.pdf

1622-MUM-2005-CORRESPONDENCE(3-10-2008).pdf

1622-mum-2005-correspondence-received-ver-091006.pdf

1622-mum-2005-correspondence-received-ver-160106.pdf

1622-mum-2005-correspondence-received-ver-210606.pdf

1622-mum-2005-correspondence-received-ver-280806.pdf

1622-mum-2005-correspondence-received.pdf

1622-mum-2005-description (complete).pdf

1622-MUM-2005-DESCRIPTION(COMPLETE)-(3-10-2008).pdf

1622-MUM-2005-FORM 1(3-10-2008).pdf

1622-mum-2005-form 2(3-10-2008).pdf

1622-MUM-2005-FORM 2(TITLE PAGE)-(21-6-2006).pdf

1622-mum-2005-form-1.pdf

1622-mum-2005-form-18.pdf

1622-mum-2005-form-2.doc

1622-mum-2005-form-2.pdf

1622-mum-2005-form-3.pdf

1622-mum-2005-form-5.pdf

1622-mum-2005-form-9.pdf

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Patent Number

234931

Indian Patent Application Number

1622/MUM/2005

PG Journal Number

28/2009

Publication Date

10-Jul-2009

Grant Date

22-Jun-2009

Date of Filing

26-Dec-2005

Name of Patentee

SALGAOCAR DILIP RAMCRISNA

Applicant Address

Sharvani Pedem, Mapusa, Goa-403507.

Inventors:

#	Inventor's Name	Inventor's Address
1	SALGAOCAR DILIP RAMCRISNA	Sharvani Pedem, Mapusa,Goa-403507

PCT International Classification Number

A61P31/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA