FORM 2
THE PATENTS ACT, 1970 (39 of 1970)
COMPLETE SPECIFICATION
(See Section 10)
A'PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
M/S. ALEMBIC LIMlTED, ALEMBIC ROAD, VADODARA - 390 003, GUJARAT, an Indian Company incorporated under the Companies Act, 1956.


The following specification particularly describes and ascertains the nature of this invention, and the manner in which it is to be performed.

This invention relates to method of preparing Rofecoxib Transdermal Gel for topical adminstration.
Peak plasma concentrations of Rofecoxib after oral administration are reached within 2 to 3 hours with an individual variability of 2 to 9 hours.
In case of acute pain in arthritis it is essential that the drug be available at the site of action rapidly to provide relief in a short period of time. Topical administration of Rofecoxib as a Transdermal Gel will provide relief from acute pain significantly faster than that compred to the oral administration.

2

According to this invention the process of preparing Rofecoxib Transdermal Gel comprt-ses the following steps :
I. Transfer Dimethyl Isosorbide, Diethylene gfycol monoethyl ether and 2-pyrroIidone to a stenm jakelted mixing tank fitted with mechanical stirrer. Warm to about 60°C
Dimethyl Isosorbide : 10.00 kg
Diethylene glycol monotehyl ether : 5.00 kg
2-pyrrolidone : 2.00 kg
2. Under stirring slowly add Rofecoxib to step 1 and continue stirring till Rofecoxib
dissolves completely. Then add under stirring Chlorocresol and dissolve.
Rofecoxib : 1.05kg
Chlorocresol : 0.1 kg
3. Transfer Glycerine and N-methyl-2-pyrrolidone to a mixing tank fitted with a
mechanical stirrer till it dissolves completely.
Glycerine : 5.00kg
N-methyI-2-pyiTolidone : 3.00 kg
4. To the mixture of step 3 add under stirring Menthol and Methyl Salicylate and stir to
dissolve completely.
Menthol : 5.0kg
Methyl Salicylate : 10.0 kg
5. Dissolve Disodium edetate in Purified water.
Disodium edetate : 0.05kg
Purified water : 5.0 kg
6. To Purified water add under stirring Poloxamer 407 slowly ar.d stir to form a uniform
dispersion. Allow the dispersion to hydrate.
Purified water : 15 kg
Poloxamer 407 : 1.00kg
7.Transfer the solution of step 2 to the dispersion of step 6 and stir to obtain smooth uniform dispersion.
3
8. Transfer the solution of step 4 to the dispersion of step 7 and stir to obtain smooth
uniform dispersion.
9. Transfer the solution of step 5 to the dispersion of step 8 and stir to obtain a smooth
uniform dispersion.
10. Transfer Linseed oil to a steam jakctted vessel and under stirring add Citric acid,
Butylatsd hydroxy anisoJs and Butylated hydroxy toluene. Heat the oi! to about 60°C
and filter the oil through a very fine sieve and allow it to coo! to 50°C.
Linseed oil : 3.00 kg
Citric acid . : 0.015kg
Butylated hydroxy anisole : 0.02 kg
Butylated hydroxy toluene : 0.02 kg
11. Transfer the Linseed oil of step 11 to the dispersion of step 10 and mix throughly.
12. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.

13. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gel is obtained.

4

A PROCESS OF 1'REPARING ROFECOXJ3 TUANSDERMAL GEL


Example -1

A PROCESS OF PREPARING ROFEXOIB TRANSDERMAL GEL
Example -1

Manufacturing Process :
1. Transfer Dimethyl Isosorbide to a steam jakettecl mixing tank fitted with
mechanical stirrer. Warm to about 60°C
Dimethyl Isosorbide : 20kg
2. Under stirring slowly add .Rorecoxib to step 1 and continue stirring till Rofecoxib
dissolves completely.
Rofecoxib : .1.05 kg
. 3. Transfer Propylene Glycol, Glycerine, 2-pyrrolidone and Polyoxyl 40 hydrogenated castor oil to a mixing tank fitted with a mechanical stirrer.
Propylene Glycol : 10.00 kg
Glycerine : 3.00kg
2-pyrrolidone ; 5.00 kg
Polyoxyl 40 hydrogenated castor oil : 5.00 kg
4, To the mixture of step 3 add under stirring Methyl paraben, Propyl paraben, Menthol and Methyl Salicylate and stir to dissolve completely.
Methyl paraben : 0.1 kg
Propyl paraben : 0.01 kg
, Menthol : 5.0kg
Methyl Salicyiate : 10.0 kg
5. To Purified water add under stirring Carbomer 940 slowly and stir to form a
uniform dispersion. Allow the dispersion to hydrate.
Purified water : 40 kg
Cabomer940 : . 1.00kg
6. Transfer solution of step no. 1 to hydrated Carbomer of step 5 under stirring. Stri
till a uniform and smooth dispersion is obtained.
7. Transfer solution of step 4 to the'dispersion of step 6 and stir to obtain smooth
uniform dispersion.
8. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.
9. Make up the weight to 100 kg with Purified water and stir till a uniform
homogenous gel is obtained.
6

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
7
Example-2


A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GE!
Example - 2 Manufacturing Process :
11. Transfer Dimethyl Isosorbide, N-methyl-2-pyrrolidone and Dielhylenc glycol
monoethyl ether to a steam jaketted mixing tank fitted with mechanical stirrer. Warm
to about 60°C
Dimethyl Isosorbide : 10.00 kg
N-methyl-2-pyrrolidone : 5.-OQ kg
Diethylene glycol monoethyl ether: 5.00 kg.
12. Under stirring slowly add Rofecoxib to step J and continue stirring till Rofecoxib
dissolves completely.
Rofecoxib : 1.05 kg
13. Transfer Propylene Glycol and Polyoxyl 40 hydrogenated castor oil to a mixing tank
fitted with a mechanical stirrer.
Propylene Glycol : 10.00 kg
Polyoxyl 40 hydrogenated castor oil : 5.00 kg
14. To the mixture of step 3 add under stirring Methyl paraben, Propyl paraben, Menthol
and Methyl Salicylate and stir to dissolve completely,
Methyl paraben : O.t kg
Propyl paraben : 0.01kg
Menthol : 5.0 kg
| Methyl Salicylate : 10.0 kg
15. To Purified water add under stirring Carbomer 980 slowJy and stir to form a uniform
dispersion. Allow the dispersion to hydrate.
Purified water : 40 kg
Cabomer980 : 1.00kg
16. Transfer solution of step no. 1 to hydrated Carbomer of step 5 under stirring. Stri till a
unjjform and smooth dispersion is obtained.

17. Dissolve Disodium edetate in Purified Water under stirring.
Disodium edetate : 0.05 kg
Purified Water : 4.00 kg
8

8. Transfer solution of step 7 to the dispersion of step 6 and stir.
9. Transfer solution of step 4 to the dispersion of step 8 and stir to obtain smooth
uniform dispersion.
10. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.
11. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gel Is obtained.
9

. A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
10
Example - 3


A PROCESS OF PREPARING ROFECOXIB TKANSDERMAL GEL
Example - 3 Manufacturing Process :
1. Transfer Dimethyl Isosorbide, Diethyiene glycol monoethyl ether and N-methyl-2-pyrrolidone to a steam jaketted mixing tank fitted with mechanical stirrer. Warm to about. 60°C
Dimethyl Isosorbide : 10,00kg
Diethyiene glycol monotehyl ether ; 3.00kg
N-methyl-2-pyrroIidone : 5.00 kg
2. Under stirring slowly add Rofecoxib to step 1 and continue stirring till Rofecoxib
dissolves completely.
Rofecoxib : 1.05 kg
3. Transfer Propyiene Gfycol, Glycerine and Isopropyl alcohol to a mixing tank fitted
with mechanical stirrer
Propyiene Glycol : 5.00kg
Glycerine : 3.00 kg
Isopropyl Alcohol : 5.00 kg
4. To the mixture of step 3 add under stirring Methyl baraben, Propyl paraben, Menthol
and Methyl Salicylate and stir to dissolve completely
Methyl paraben : 0.1 kg
PropyJ paraben : 0.01kg
Menthol : 5.0kg
Methyl Salicylate : 10.0kg
5. To Purified water add under stirring Carbomer 940 movf\y ^4 stir to form a uniform
dispersion. Allow the dispersion to hydrste,.
Purified water : 40 kg
Cabomer940 : 1.00kg

6. Transfer Cetostearyl Alcohol and Cetomacrogol 1000 to a steam jaketted vessei and
heat it to 70° and stir.
7. Heat the dispersion of Carbomer 940 of step 5 to 70°b
8. Transfer the mix of step 6 to the dispersion of sttp 7 and stir to obtain Smooth
uniform dispersion and allow it to cool to about 50°C,
9. Transfer the solution of step 2 to the dispersion of step 8 and stir to obtain smooth
uniform dispersion.
11

10. Transfer the solution of step 4 to the dispersion of step 9 and stir to obtain a smooth uniform dispersion.
11.-Transfer Linseed oil to a steam jaketted vessel and under stirring add Citric acid, Butylated hydroxy anisole and Butylated hydroxy toluene. Heat the oil to about 60°C and filter the oil through a very fine sieve and allow it to cool to 50°C.
Linseed oil : 3.00 kg
Citric acid : 0.015kg
Butylated hydroxy anisole : 0.02 kg
ButyJated hydroxy tolune : 0.02 kg
12. Transfer the Linseed oil of step 11 to the dispersion of step 10 and mix throughly.
13. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Triethanolamine in Purified water.
14. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gel is obtained.

12

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
Example - 4

13

j A PROCESS OF PREPARING ROFECOXIB TRANSDERMAI, GEL
Example - 4 Manufacturing Process :
5. Transfer Dimethyl ]sosorbide, Diethylene glycol monoethyl ether and 2-pyrrolidone to a steam jaketted mixing tank fitted with mechanical stirrer. Warm to about 60°C
Dimethyl Isosorbide : 10.00 kg
Diethylene glycoi monotehy! ether : 5.00 kg
2-pyrrolidone : 2.00 kg
6. Under stirring slowly add Rofecoxib to step 1 and continue stirring till Rofecoxib
dissolves completely. Then add under stirring Chlorocresol and dissolve.
Rofecoxib : 1.05kg
Chlorocresol : 0.1 kg
7. Transfer Glycerine and N-methyl-2-pyrrolidone to a mixing tank fitted with a
mechanical stirrer till it dissolves completely.
Glycerine : 5.00kg
N-methyl-2-pyrrolidone : 3.00 kg
8. To the mixture of step 3 add under stirring Menthol and Methyl Salicylate and stir to
dissolve completely.
Menthol : 5.0 kg
Methyl Salicylate : 10.0kg
5. Dissolve Disodium edetate in Purified water.
Disodium edetate : 0.05 kg
Purified water : 5.0 kg
6. To Purified water add under stirring Poloxamer 407 slowly and stir to form a uniform
dispersion. Allow the dispersion to hydrate.
Purified water : . 15 kg
Poloxamer 407 : 1.00 kg
7.Transfer the solution of step 2 to the dispersion of .step 6 and stir to obtain smooth uniform dispersion.

14

18. Transfer the solution of step 4 to the dispersion of step 7 and stir to obtain smooth
uniform dispersion.
19. Transfer the solution of step 5 to the dispersion of step 8 and stir to obtain a smooth
uniform dispersion.
- 20. Transfer Linseed oil to a steam jakefted vessel and under stirring add Citric acid, Butylated hydroxy anisole and Butylated hydroxy toluene. Heat the oil to about 60°C and filter the oi! through a very fine sieve and allow it to cool to 50°C.
Linseed oil : 3.00kg
Citric acid : 0.015kg
Butylated hydroxy anisole : 0.02 kg
Butylated hydroxy toluene : 0.02 kg
11. Transfer the Linseed oil of step 11 to the dispersion of step 10 and mix throughly.
12. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.
13. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gei is obtained.

15

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
16
Example - 5

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
Example-5 Manufacturing Process :
1. Transfer Dimethyl Isosorbide and N-methyl-2-pyrrolidone to a steam jakclled mixing tank fitted with mechanical stirrer. Warm to about 60°C
Dimethyl Isosorbide : 10.00kg
N-methyl-2-pyrrolidone : 5.00 kg
2. Under stirring slowly add Ro/ecoxib to step 1 and continue stirring tiii Rofecoxib
dissolves completely. Then add under stirring Chlorocresol and dissolve.
Rofecoxib : 1.05kg
Chlorocresol : 0.1 kg
3. Transfer Propylene Glycol and Polyoxyl 40 hydrogenated castor oil to a mixing tank
fitted with a mechanical stirrer till it dissolves completely.
Propylene Glycol : 10.00kg
Polyoxyl 40 hydrogehated castor oi! : 5.00 kg
4. To the mixture of step 3 add under stirring Menthol and Methyl Salicylate and stir to
dissolve completely.
Menthol : 5.0 kg
Methyl Salicyiate : 10.0kg
5. Transfer Giyceryl stearate and polyethylene glycol 75 stearate to a steam jacketted
vessel and heat it to 70°C.
Giyceryl stearate and polyethylene glycol 75 stearate : 15.0 kg
6. Transfer Purified water to a steam jacketted vessel and disperse carbomer 980 under
stirring. After the carbomer has hydrated completely, heat it to 70°C.
Carbomer 980 : 0.5 kg
1'7

7. Transfer the mix of step 5 to the dispersion of step 6 and stir to obtain smooth
uniform dispersion.
8. Transfer the solution of step 2 to the dispersion of step 7 and stir to obtain a smooth
uniform dispersion.
9. Transfer the solution of step 4 to the dispersion of step 8 and stir.
10.Transfer Linseed oil to a steam jaketted vessel and under stirring add Citric acid, Butylated hydroxy anisole and .Butylatedhydroxy toluene. Meat the oil to about 60°C and filter the oil through a very fine sieve and allow it to cool to 50°C.
Linseed oil : 3.00 kg
Citric acid : 0.015kg
Butylated hydroxy anisole : 0.02 kg
Butylated hydroxy toluene : 0.02 kg
11. Transfer the Linseed oil of step 10 to the dispersion of step 9 and mix throughly.
12. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.
13. Make up the weight to 100 kg with Purified water ami stir till a uniform homogenous
gel is obtained.
18

A PROCESS OF PREPARING ROFECOXIB TRANSOERMAL GEL
19
Example - 6


A PROCESS OF PREPARING ROFECOXIb TRANSDERMAL GEL
Example - 6 Manufacturing Process :
1. Transfer Dimethyl Isosorbide and 2-pyrrolidone to a steam jaketted mixing tank fitted with mechanical stirrer, Warm to about 60°C
Dimethyl Isosorbide : 10.00 kg
2-pyrrolidone : 3.00kg
2. Under stirring slowly add Rofecoxib to step 1 and continue stirring til! Rofccoxib
dissolves completely.
Rofecoxib : 1.05 kg
3. Transfer Propylene Glycol, Glycerine and Polyoxyl 40 hydrogenated'castor oil to a
mixing tank fitted with a mechanical stirrer.
Propylene Glycol : 10.00 kg
Glycerine : 2.00 kg
Polyoxyl 40 hydrogenated castor oil : 5.00 kg
4. To the mixture of step 3 add under stirring Chlorocresol, Menthol and Methyl
Salicylate and stir to dissolve completely.
Chlorocresol : 0.1 kg
Menthol : 5.0 kg
Methyl Salicylate : 10.0kg
5. To Purified water add under stirring Carbomer 974 P and Poloxamer 407 slowly and
stir to form a uniform dispersion. Allow the dispersion to hydrate.
Purified water : 40 kg
Cabomer 974 P - : 0.50 kg
Poloxamer 407 : 10.00kg
6. Transfer solution of step noi 1 to the dispersion of step no. 5 under stirring. Stri till a
uniform and smooth dispersion is obtained.
i
7. Transfer solution of step 4= to the dispersion of step 6 and stir to obtain smooth
uniform dispersion. :

8. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of Sodium
Hydroxide in Purified water.
9. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gel is obtained.
20

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
21
Example - 7


A PROCESS OF PREPARING ROFECOXJB TRANSDERMAL GEL
Example-7 Manufacturing Process :
1. Transfer Polyoxyl 40 hydrogenalcd castor oil and N-methyi-2-pyrrolidonc to a mixing
tank fitted with a mechanical stirrer.
Polyoxyl 40 hydrogenated castor oil : 5.00 kg
N-methyl-2-pyrrolidone : 5.00kg
2. To the mixture of step 1 add under stirring Menthol and Chlorocreso! and stir to
dissolve completely.
Menthol : 5.0kg
Chlorocresoi : 0.1 kg
3. Transfer Purified water to a steam jacketted vessel and disperse carbomer 940 under stirring. Allow the carbomer to hydrate completely.
Carbomer 940 : 1.00kg
4. Transfer the solution of step 2 to the dispersion of step 3 and stir to obtain a smooth uniform dispersion.
5.Transfer Linseed oil to a steam jaketted vessel and under stirring add Citric acid, Butylated hydroxy anisole and Butylated hydroxy toluene. Heat the oil to about 60°C and filter the oil through a very fine sieve and allow it to cool to 50°C. •
Linseed oil : 3.00kg
Citric acid : 0.015kg
Butylated hydroxy anisole : 0.02 kg
Butylated hydroxy -oiuene : 0.02 kg
Transfer the Linseed oil of step 5 to the dispersion of step 4 and mix throughly.

7. Adjust the pH of the dispersion to about 4 to 6.8 using 20% w/v solution of
Tromethamine in Purified water.
8. To the dispersion of step 7, add under homogenisation Rofecoxib slowly and continue
homogenisation till Rofecoxib is completely and uniformly dispersed.
Rofecoxib : 1.05 kg
9. Make up the weight to 100 kg with Purified water and stir till a uniform homogenous
gel is obtained.
22

A PROCESS OF PREPARING ROFECOXIB TRANSDERMAL GEL
Example - 8

23

A PROCESS OF PREPARING ROFECOXIB TRANSDEUMAL GEL
Example-8 Manufacturing Process :
1. Transfer Dimethyl Isosorbide and 2-pyrrolidone to a steam jaketted mixing tank fitted wiih mechanical stirrer. Warm to about 60°C
Dimethyl Isosorbide : 10.00 kg
2-pyrrolidone : 5.00kg
2. Under stirring slowly add Rofecoxib to step I and continue stirring till Rofecoxib
dissolves completely. Then add under stirring Chlorocresol and dissolve.
Rofecoxib : 1.05 kg
Chlorocresol : 0.1 kg
3. Transfer Propylene Glycol and Polyoxyl 40 hydrogenated castor oil lo a mixing tank
fitted with a mechanical .stirrer till it dissolves completely.

Propylene Glycol : 10.00 kg
Polyoxyl 40 hydrogenated castor oil : 5.00 kg
4. To the mixture of step 3 add under stirring Menthol and Methyl Salicylate and stir to
dissolve completely.
Menthol : 5.0kg
Methyl Salicylate : 10.0kg
5. Transfer Polyethylene Glycol-6-32 stearate and Glycol stearate, Burylated hydroxy anisole and Butylated hydroxy toluene to a steam jacketted vessel and heat it to 70°C.
Polyethylene gtycol-6-32 stearate : 20.0 kg
and Glycol stearate
Butylated hydroxy anisole : 0.02 kg
Butylated hydroxy toluene : 0.02 kg
6. Transfer Purified water to a steam jacketted vessel and disperse carbomer 980 under stirring. After the carbomer has hydrated completely, heal it lo 70°C.
Carbomer 980 : 0.5 kg

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We claim :

l.A process of preparation of Rofecoxib Transdermal Gel for administering an
effective amount of Rofecoxib in a pharmaceutically acceptable delivery vehicle for
- topical application.
2. A process of preparation of Rofecoxib TransdermaP'Gcl for administering an effective amount of Rofecoxib in combination with Menthol, Methyl SalicySate, Linseed oil and mixtures thereof in a pharmaceutically acceptable deiivery vehicle or topical application.
3. The pharmaceutical composition of claim J ana claim 2, the process for which is described herein comprising pharmaceutically acceptable solubilisers, penetration enhancers, thickening agents, surfactants, preservatives, chelating agents, antioxidants and pH adjusting agents.
4. The process for making the pharmaceutical composition wherein the said
solubilisers, penetration enhancers, surfactants is selected from the group consisiting
of Polyoxyl 40 hydrogenated castor oil, Propylene glycol, Glycerin, 2-pyrrolidone,
Dimethyl Isosorbide, Diethylene Glycol mnnocthyl ether. Isopropyl alcohol, N-
melhyl-2-pyrrolidone.
5. The process for making the pharmaceutical composition of claim 1 and claim 2,
wherein the said thickening agents is selected from the group consisting of
Carbomers, Poloxamers Glyceryl Stearatc and Polyethylene Glycol 75 stearate,
Polyethylene Glycol-6-32 stearate and Glycol Stearatc, Cetostearyl alcohol and
CefomacrogoJ 1000.
6. The process for making the pharmaceutical composition of claim 1 and claim 2;
wherein the said preservatives is selected from the group consisting of Methyl
paraben, Propyl paraben, Chlorocresol.
7. The process for making the pharmaceutical composition of claim 1 and claim 2,
wherein the said chelating and/or antioxidants is selected from Disodium edetate,
Citric acid, Butylated hydroxy anisole and butylated hydroxy toluene.
8. The process for making the pharmaceutical composition of claim 1 and claim 2,
wherein the said pH adjusting agents is selected from Citric acid, Triethanolamine,
Tromethamine, Sodium Hydroxide.
9. The process for making the pharmaceutical composition of claim 1 and claim 2,
where by Rofecoxib is dissolved in part quantity of solubilisers, penetration
enhancers and surfactants and mixtures thereof as described in claim 4.
10. The process for making the pharmaceutical composition of claim 1 and claim 2,
where by preservatives as described in claim 6 and Menthol and Methyl Salicylate as
described in claim 1 are dissolved in another part quantity of solubilisers, penetration
enhancers and surfactants and mixtures thereof as described in claim 4.
11. The process for making the phrmacejaticaDcom position of claim land claim 2, where
by the thickening agents as described in claim 5 are dispersed in Purified water.
12. The process for making the pharmaceutical composition of claim 1 and claim 2,
where by the cheJating agents like Disodium edetate is dissolved in Purified water.
13. The process for making the pharmaceutical composition of claim 2, where by the
chelating agents like Citric acid is added to Linseed oil and heated to about 60° - 70
°C «nd filtered. The antioxidants as described in claim 7, Butylated hydroxy anisole
and butylated hydroxy toluene are added to the above Linseed oil and stirred tiff it
attains ambient temperature.
14. The process for making the pharmaceutical composition of claim 1 and claim 2, where by the solution of Rofecoxib of claim 9 is added to the dispersion of thickening agent as described in claim .
25

15. The process for making the pharmaceutical composition of claim 1 and claim 2,
further incorporating the solution of the chelating agents as described in claim 12 to
the dispersion obtained as described in claim 14.
16. The process for making (he pharmaceutical composition of claim 1 and claim 2.
further involving the addition of solution obtained as described in claim 10 fo !hc
dispersion of claim 15.
17. The process for making the pharmaceutical composition of claim 2, where by the
Linseed oil as described in claim 13 is added to the dispersion of claim 16.
18. The process for making the pharmaceutical composition of claim 1 and claim 2,
where by the pH of the dispersion of claim 17 is adjusted between A - 6.8 using the
pH adjusting agents as described in claim 8.
19. The process for making the pharmaceutical composition of claim 1 and claim 2,
where by the final weight make up of the dispersion of claim 18 is done by addition
of Purified water to obtain Rofecoxib Transdermal Gel.
Dated this 31st October 2001

26