PiroGl

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PIROXICAM GEL

No Description Section No

1. Drug Authority Application form

2. Name and Address of Applicant *& Manufacturer

3. Name of the Product4 Free Sale certificate I

5. Certificate II

6. Certificate of the composition of the product giving in detail the

chemistry of the active ingredient / ingredient of the product.

ill

7. Detailed specification and standards laid down by the manufacturerfor each product together with its method of analysis in details.

IV

8. A certificate of sterility and absence ofpyrogen wherever it isapplicable

V

9. Six samples of the product applied for registration in their originalpack.

VI

10. Certificate of Analysis VII

11. Reference Sample VIII

12. Bioavailability studies I IX

13. Safety and Tolerance studies & Test X

14. Detailed Reports covering a) Pharmacologicalb)Toxicologicalc)

Clinical aspectsXI

15. Storage Date XII

16. Authenticated price list XIII

17. Name of the competitive drugs manufactured by other firms XIV

18. Other countries where the product is Registered XV

19. Date of introduction of the product to the market in the country oforigin. XIV

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COMPOSITION OF THE PRODUCT

PRODUCT:ROXICAM GELBatch No. :01 Batch Size : 300.0 kgs

NO INGREDIENTS SPEC. LABEL CLAIMW/W OVER

AGES

QTY IN

KGS

1 Piroxicam IP 0.50 % 5.0 % 1.575

2 Carbomer934 USP 0.90 % 2.700

3 Glycerin IP 10.00 % 30.000

4 Propyleneglycol IP 20.00 % 60.000

5 Potassium Hydroxide IP 0.80 % 2.4006 DisodiumEdetate IP 0.01 % 0.030

7 Methyl Paraben IP 0.16% 0.480

8 Propyi Paraben IP 0.04 % 0.120

9 D.M.WaterQ.S. to IP 300.000

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CHEMICAL NAME & STRUCTURAL FORMULA OF EACH

ACTIVE INGREDIENT

DRUG NAME : Piroxicam

SYNONYM

MOLECULAR FORMULA : C15Hi3N304S

CHEMICAL NAME : 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-

benzothiazine -3-carboxamide-l,l-dioxide

SPECIFICATION OR : I.P - 1996 ; Page No. 600

REFERENCE TEXT

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INACTIVE INGREDIENTS

PRODUCT: ROXICAM GEL

Batch No. :01 Batch Size : 300.0 kgs

NO INGREDIENTS SPE. LABEL

CLAIM

OVER

AGES

QTYIN KGS

REASON FOR

INCLU.

1 Carbomer934 USP 0.90 % 2.700 Suspending & gellingagent

2 Glycerin IP 10.00% 30.000 Humectant

3 Propyleneglycol IP 20.00% 60.000 Humectant & solvent

4 Potassium Hydroxide IP 0.80% 2.400 PH adjuster

5 DisodiumEdetate IP 0.01% 0.030 Chelating/com plexing

agent.6 Methyl Paraben IP 0.16% 0.480 Antimicrobial

preservative

7 Propyi Paraben IP 0.04% 0.120 Antimicrobial

Preservative

8 D.M.Water Q.S.to IP 300.00 Solvent

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RAW MATERIAL SPECIFICATION AND

ANALYTICAL CONTROL PROCEDURE

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RAW MATERIAL : PIROXICAM

PROTOCOL : IP - 1996 PAGE : 01 OF 03

C15H13N304S Mol.Wt. 331.35

Piroxicam is 4-hydroxy-2-metfayl-N-(2-pyridyl)-2H-l,2-benzothiazine -3-carboxamide-

1,1- dioxide.

CATEGORY:

Analgesic; antiinflammatory; antipyretic.

DOSE :

10 to 20 mg daily.

DESCRIPTION :Off-white to light tan or light yellow powder; odourless.

SOLUBILITY:

Slightly soluble in ethanol (95%) and in aqueous alkaline solutions; very slightly soluble

in water, in dilute acids and in most organic solvents.

STORAGE:

Store in tightly-closed, light resistant containers .

STANDARDS:

Piroxicam contains not less than 97.0 per cent and not more than 103.0 percentofC15H13N3O4S, calculated with reference to the anhydrous substance.

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RAW MATERIAL :PIROXICAM

PROTOCOL : IP - - 1996 PAGE . 02 OF 03

IDENTIFICATION :

A. The infrared absorption spectrum. Appendix 5.4, is concordant with the reference

spectrum ofpiroxicam or with the spectrum obtained frompiroxicamRS.

B. The light absorption in the range 230 to 360 nm of a 0.001% w/v Solution in 0.01

Mmethanolic hydrochloric acid exhibits two maxima, at about 242 nm and 334

nm and a minimum at about 270 nm; absorbance at about 334 nm, about 0.87,

Appendix 5.5.

C. Carry out the method for thin layer chromatography. Appendix 4.6, using silica

gel GF254 as the coating substances and a mixture of 95 volumes of toluene and 5

volumes of acetic acid as the mobile phase but allowing the solvent front toascend 15 cm above the line of application. Apply separately to the plate 20 jul of

each of the two solutions in a mixture of equal volumes of chloroform andmethanol containing (1) 0.1 % w/v of the substance being examined, (2) 0.1 %

w/v of piroxicam RS . Allow it to dry and develop again. After removal of the

plate allow it to dry in air and examine under ultra-violet light (254 nm). The

principal spot in the chromatogram obtained with solution (1) corresponds to thatin the chromatogram obtained with solution (2).

HEAVY METALS:

Not more than 50ppm, determined on 0.4 g by Method B, Appendix 3.12.

SULPHATED ASH :

Not more than 0.3 %, Appendix 3.22.

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RAW MATERIAL :PIROXICAM


WATER:

Not more than 0.5 %w/w, determined on 2.0 g, Appendix 3.24.

ASSAY:

Carry out the method for high performance liquid chromatography, Appendix 4.3, usingdie following solutions in 0.1 Mmethanolic hydrochloric acid containing (1) 0.005% w/v

of the substance being examined and (2) 0.005 % w/v of piroxicamRS.

The Chromatographic procedures may be carried out using (a) a stainless steel columnpacked with stationary phase LCI,(b) a degassed mixture of 45 volumes ofmethanol and

55 volumes of a buffer solution prepared by diluting a mixture of 7.72 g of anhydrous

citric acid in 400 ml of water and 5.35 g of sodium phosphate in 100 ml of water to 1000

ml with water as the mobile phase with a flow rate of 1.2 ml per minute and (c) adetection wavelength of about 254 run.

The column efficiency determined using solution (2) is not less than 500 theoretical

plates, the tailing factor is not more than 1.5. The test is not valid unless the relative

standard deviation for replicate injections is not more than

2.0 %.

Calculate me content of C15H13N3O4S inpiroxicam RS.

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TEST CERTIFICATE

(THE DRUGS AND COSMETICS ACT 1940 AND THE RULES

THEREUNDER FORM 39 )

RAW MATERIAL :PIROXICAM IPParty : Universal Impex A.R.NO. : UIR 257/98-99

G.R.N.no. :UI/RM/250/989 Pub. Lab. T.R.NO. : R07556

Batch No. :PX-036/98 Mfg. Date : Dec' 1998

Batch Size : 1x5 kg = 5 kg Exp. Date :Nov'2003

Manufacturer:RamdevChem Dt of Receipt : 24/01/99

Supplier:ReamdevChem DtofCompletion : 30/01/99

Ch.No./Dt: 243/24-01-99 Qty sampled : 2x5g

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS PER IP-96

Protocols Results Claim / Limit

Description Complies with IP Off-white to light tan or

light yellow powder;

odourless.

Solubility Complies with IP

Identification A,B,C Complies with IP

Heavy metals. Complies with IP NMT 50 PPM

Sulphated ash 0.03989 % NMT 0.3 %

Water 0.2975 % w/w NMT 0.5% w/w

Assay as C15H13N3O4S 98.7 % OAB 97.0% to 103.0%

OPINION : In the opinion of the undersigned, the sample referred to above is of standardquality as defined in the act and the rules thereunder with respect to the tests carried out

and mentioned above as per IP-96.

Date : 30/01/99 Analyst Q.C.Incharge.

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RAW MATERIAL :CARBOMER934

PROTOCOL :USP PAGE: 01 OF 04

Carbomer934 is a high molecular weight polymer ofacrylic acid cross-linked with allylethers of sucrose. Carbomer 934, previously dried in vacuum at 80 deg for 1 hour,

contains not less than 56.0 percent and not more than 68.0 percent ofcarboxylic acid

(-COOH) groups. The viscosity of a neutralised 0.5 percent aqueous dispersion ofCarbomer 934 is between 30,500 and 39,400 centipoises.

PACKAGING AND STORAGE :

Preserve in tight containers.

LABELLING :Label it to indicate that it is not intended for internal use.

IDENTIFICATION :-

A. Prepare a 1 in 100 dispersion of it To one portion of the dispersion add thymol

blue TS: an orange color is produced. To another portion of the dispersion add

cresol red TS: a yellow color is produced.

B. Adjust a 1 in 100 dispersion of it with 1N sodium hydroxide to about Ph 7.5: avery viscous gel is produced.

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PROTOCOL :USP PAGE : 02 OF 04

VISCOSITY ; (911)

Carefully add 2.5 gm, previously dried in vacuum at 80 deg for 1 hour, to 500 ml ofwater in a 1000 ml beaker, while stirring continuously at 1000 +/- 10 rpm, with the

stirrershaft set at an angle of 60 deg and to one side of the beaker , with the propeller

positioned near the bottom of the beaker. Allow 45 to 90 seconds for the addition of thetest preparation at a uniform rate, being sure that loose aggregates of powder are broken

up, and continue stirring at 1000 +/- 10 rpm for 15 minutes. Remove the stirrer, and

place the beaker containing the dispersion in a 25 +/- 0.2 deg water bath for 30 minutes.

Insert the stirrer to a depth necessary to ensure that air is not drawn into the dispersion,and while stirring at 300 +7- 10 rpm, titrate (see Titrimetry (541) with a calomel-glass

electrode system to a pH of between 7.3 and 7.8 by adding sodium hydroxide solution

(18 in 100) below the surface, determining the end point potentiometrically. The total

volume of sodium hydroxide solution (18 in 100) used is about 6.2 ml . Allow 2 to 3minutes before the final pH determination. [ Note If the final pH exceeds 7.8, discard

the mucilage , and prepare another using a smaller amount of sodium hydroxide fortitration]

Return the neutralized mucilage to 25 deg water-bath for 1 hour, then perform theviscosity determination without delay to avoid slight viscosity changes that occur 75

minutes after neutralization. Equip a suitable rotational viscometerwith a spindle having

a cylinder 1.47 cm in diameter and 0.16 cm high attached to a shaft 0.32 cm in diameter,

the distance from the top of the cylinder to the lower tip of the shaft being 3.02 cm, andthe immersion depth being 4.92 cm (No. 6 spindle). With the spindle rotating at 20 rpm,

observe and record the scale reading. Calculate the viscosity , in centipoises, bymultiplying the scale reading by the constant for the spindle used at 20 rpm.

LOSS ON DRYING:

(731)Dry it in a vacuum at 80 deg for 1 hour; it loses not more than 2.0 % of its weight.

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HEAVY METALS:

Method II (231): 0.002%

BENZENE:

Standard preparation : Transfer 5.7 ul (5 mg) of benzene to a 500 ml volumetric flask,

add water to volume, and mix until homogeneous. Dilute 10.0 ml of this mixture with

water to 500 ml , and mix. Pipet 5 ml of this solution into a suitable 10 ml serum-type

vial, insert a tight rubber stopper, and seal with a metal cap.

Test preparation : Accurately weigh about 10 mg of carbomer into a suitable 10 ml

serum-type vial, add 5 ml of water, insert the stopper without delay, seal the vial, and

mix to dissolve the specimen.

Chromatographic system : (see Chromatography (621) The gas chromatograph isequipped with a flame-ionization detector and a 2-mmx 1.8-m column packed with 0.2

% phase G39 on support S7. The injector and detector are maintained at temperatures of

about 200 deg. The column temperature is maintained at 80 deg for 4 minutes, then

raised at the rate of 5 deg per minute to 150 deg. The carrier gas is nitrogen , flowing at arate of 20 ml per minute. Treat and inject the Standard preparation as directed under

procedure, and measure the peak response for benzene. The relative standard deviation

for replicate injection is not more than 5.0 %

PROCEDURE : - [ In the following chromatographic procedure, the use ofheadspaceapparatuses that automatically transfer the measured amount ofheadspace is preferable tohandling heated syringes for injecting the heated specimen.] Immerse the vials up to the

rim of the cap in a thermostatic bath, maintained at a temperature of 85 deg , for at least

30 minutes. Using a 2 ml of gas syringe preheated in an oven at 100 +/- 2 deg, inject

rapidly 1.0 ml of the gaseous phase from each vial separately into the chromatograph, andmeasure the peak responses for benzene. Calculate the quantify , in ug, of benzene in the

weight of specimen taken by the formula :

ru/rs,

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RAW MATERIAL : CARBOMER934


in which ru and rs, are the responses obtained from the Test preparation and Standard

preparation , respectively. The weight of benzene found is not more than 0.01 % of theweight of the specimen taken.

ASSAY FORCARBOXYLIC ACID CONTENT :

Slowly add about 400 mg previously dried and accurately weighed , to 400 ml of water

in 1000 ml beaker, while stirring continuously at about 1000 rpm, with the stirrershaft

set at an angle of 60 deg and at the side of the beaker, with the propeller positioned nearthe bottom of the beaker, and continue stirring for 15 minutes. Reduce the stirring speed,

and titrate potentiometrically with 0.25N sodium hydroxide VS, using calomel glass

electrode system. Allow 1 minute for mixing , after each addition of 0.25 N sodium

hydroxide VS, before recording the pH. Calculate the carboxylic acid content as apercentage of carboxylic acid groups taken by the formula

100 (45.02VN/W),

in which V is the volume in ml, of sodium hydroxide consumed, N is the normality ofsodium hydroxide solution ,W is the weight, in mg, of the specimen taken , and 45.02 is

the molecular weight of the carboxylic acid (- COOH) group.

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TEST CERTIFICATE


THEREUNDER FORM 39)

Rawmaterial:Carbomer934 USPParty : Universal Impex A.R.NO. : UIR 287/98-99

G.R.N. No. : UI/RM/279/989 Pub. Lab. T.R.NO. : R10400

Batch No. : KK832KA459 Mfg. Date :Mar'1999

Batch Size : lx22.68kg-22.68kg Exp. Date :-

Manufacturer: Goodrich Dt of Receipt : 23/03/99

Supplier: Hemlin Chemicals Dt of Completion ; 28/03/99

Ch.No./Dt : 22-03-99 Qty sampled : 2xl5g

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS

PER USP


Description Complies with USP White, fluffy powder having a

slight characteristic odour,

hygroscopic, the pH of a 1 in100 dispersion is 3.20.

Solubility Complies with USP

Identification A, B Complies with USP

Viscosity 31060cps 30500 39400 cps

Benzene Test Passes NMT 0.5 %

Loss on drying 0.45 % NMT 2.0 %

Heavy metals Complies with USP NMT 0.002 %Content ofcarboxylic acid 66.11%ODB 56.0 % -68.0 %

OPINION: In the opinion of the undersigned, the sample referred to aboveis of standard quality' as defined in the act and the rules thereunder with

respect to the tests carried out and mentioned above as net USP

Date : 28-03-99 Analysis Q.C.Incharge.

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RAW MATERIAL : GLYCERIN


GLYCEROL

Glycerin is propane- 1,2,3-triol

CATEGORY:

Lubricant; laxative; pharmaceutical aid (humectant)

DESCRIPTION :

Clear, colourless or almost colourless, syrupy liquid; odourless; very hygroscopic.

SOLUBILITY:

Miscible with water and with ethanol (95 %); slightly soluble in acetone; practically

insoluble in ether and in fixed oils and volatile oils.

STORAGE:

Store in tightly-closed containers.

STANDARDS:

Glycerin contains not less than 98.0 per cent and not more than 101.0 per cent of

C3H8O3, calculated with reference to the anhydrous substances.

IDENTIIFCATION:

Test A be omitted if test B,C and D are carried out. Test B and C may be omitted if test

A and D are carried out.

A : To 5 ml add 1 ml of water and mix carefully. The infra-red absorption spectrum of

the resulting solution. Appendix 5.4, is concordant with the reference spectrum of

glycerin (85 %) or with the spectrum obtained from glycerin (85 %)RS.

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B: Mix 1 ml with 0.5 ml of nitric acid and superimpose 0.5 ml of potassium

dichromate solution; a blue ring develops at the interface of the two liquids.Allow to stand for 10 minutes ; the blue colour does not diffuse into the lower

layer.

C: Heat 1 ml with 2 g of potassium hydrogen sulphate in an evaporating dish. Irritant

vapours are evolved which blacken filter paper moistened with alkaline potassium

mercuri-iodide solution.

D: Refractive index, between 1.470 and 1.475, determined at 20 ,

Appendix 8.13.

ACIDITY OR ALKALINITY:

To 50 ml of a 50.0 % w/v solution in carbon-dioxide free water( solution A) add 0.5 mlofphenolphthalein solution. The solution is colourless and not more than 0.2 ml of 0.1 M

sodium hydroxide is required to produced a pink colour. Reserve the final solution for

the test for Ester

CLARITY AND COLOUR OF SOLUTION :

Solution A is clear. Appendix 6.1. Dilute 10 ml of solution A to 25 ml with water . The

solution is colourless. Appendix 6.2

HEAVY METALS:

Not more than 5ppm, determined by Method A on a solution of 4.0 g in 2 ml of 0.1 M

hydrochloric acid and sufficient water to produce 25 ml,

Appendix 3.12.

IRON:

10 g complies with the limit test for iron. Appendix 3.13 (4 ppm).

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CHLORIDE:

20 ml of solution A complies with the limit test for chlorides , Appendix3.10(25ppm).

SULPHATE:

10 ml of solution A complies with the limit test for sulphates , Appendix 3.15(30ppm).

ALDEHYDES AND REDUCING SUBSTANCES :

To 7.5 ml of solution A in a glass stoppered flask add 7.5 ml of water and 1 ml of

decolorised pararosaniline solution, close the flask and allow to stand for 1 hour. Any

color produced is not more intense than that obtained in a standard prepared at the sametime and in the same manner but using 7.5 ml of formaldehyde standard solution ( 5ppm

CH2O) in place of solution A.The test is not valid unless the standard solution is pink.

ESTER:

Add 0.1 M sodium hydroxide to the solution reserved in the test for Acidity or alkanity

until a total of 10.0 ml has been added and boil under reflux condenser for 5 minutes .

Cool, add 0.5 ml ofphenolphthalein solution and titrate with 0,1 M hydrochloric acid.Not less than 8.0 ml of 0.1 M hydrochloric acid is required to decolorise the solution.

GLYCOLS AND RELATED SUBSTANCES :

Carry out the method for thin-layerchromatography. Appendix 4.6, using silica gel G as

the coating substance and a freshly prepared mixture of 55 volumes of chloroform , 35

volumes of acetone and 10 volumes of ethanol (95%) as the mobile phase. Applyseparately to the plate 5 pi of each of the following solution. Solution (1) is a 2.0 % w/v

solution of the substances being examined. Solution (2) contains 0.02 % w/v each

ofdiethyleneglycol RS,ethylene glycol RS andpropylene glycol RS in ethanol (95 %).

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After removal of the plate, allow it to dry in air for 1 hour, spray with a 0.1 % w/v

solution of sodium metaperiodate and dry me plate in a current of warm air. Spray with asolution prepared by dissolving 1.8 gofbenzidine in 50 ml ofetfaanol (95 %), adding 50

ml of water followed by 20 ml of acetone and 10 ml of 0.2 M hydrochloric acid. Allow

the plate to dry in air.Any secondary spot in the chromatogram obtained with solution (1) is not more intense

than any of the spots in the chromatogram obtained with solution (2).

SUGARS :

Heat 10 ml of solution A with 1 ml of 1 M sulphuric acid on a water bath for 5 minutes .

Add 3 ml of 2 M Sodium hydroxide ( Carbonate-free), mix and add dropwise 1 ml of

freshly prepared copper sulphate solution; a clear blue solution is produced. Continue

heating on the water-bath for 5 minutes; me solution remains blue and no precipitate isproduced.

SULPHATE ASH:

Not more than 0.01 %, determined on 5 g, appendix 3.22.

WATER:

Not more than 2.0 % w/w, determined on 1.5 g. Appendix 3.24.

ASSAY:

Weigh accurately about 0.1 g, mix throughly with 45 ml of water, add 25.0 ml of a 2.14

% solution of sodium periodate and 1 ml of 1 M sulphuric acid and allow to standprotected from light for 15 minutes. Add 5 ml of a 50 % w/v solution ofethyleneglycol,allow to stand protected from light for 20 minutes and titrate with 0.1 M sodium

hydroxide using 0.5 ml ofphenolphthalein solution as indicator. Perform a blank

determination and make any necessary correction. Each ml of 0.1 M Sodium hydroxide

is equivalent to 0.00921 g of C3H8O

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TEST CERTIFICATE

( THE DRUGS AND COSMETICS ACT 1940 AND THE RULES


Rawmaterial: Glycerine IPParty : Universal Impex A.R.NO. :UIR 228/98-99

G.R.N.No.:UI/RM/223/989 Pub. Lab. T.R.NO.

Batch No. :E0804-14 Mfg. Date

Qty received : 1 x 250 kg. = 250.0 kg. Exp. Date

Manufacturer: Dt of Receipt 06/12/98

Supplier:Sneha chemicals Dt ofCompletion 15/12/98

Ch.No*/Dt:Proforma/ 02-12-98 Qty sampled 2 x 100 ml

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS PERIP -96.


Description Complies with IP Clear, colourless,

syrupy liquid;

odourless; veryhygroscopic.


Identification - B,C, D Complies with IP D-1.474 1.470 to 1.475

Acidity & alkalinity Complies with IP

Clarity & colour of sol. Complies with IP

Heavy metals Complies with IP NMTSppm

Iron Complies with IP NMT 4ppmChloride Complies with IP NMT 25 ppm

Sulphate Complies with IP NMT 30 ppm

Aldehydes & Reducing sub. Complies with IP

Esters Complies with IP

Glycols& Related sub Complies with IP

Sugars Complies with IP

Sulphated ash 0.01996 % NMT 0.01 %

Water 0.88499 % w/w NMT 2.0% w/w

Assay as C3H8O. 98.6141 % OAB 98.0 % to 101.0 %

OPINION :In the opinion of the undersigned, the sample referred to above is of standard

quality as defined in the act and the rules thereunderwith respect to the tests carried out

and asestiened above as per IP-96 - 96

Date : 15-12-98 Analyst Q.C. Incharge.

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RAW MATERIAL :PROPYLENE GLYCOL


1,2-PROPANEDIOL

C3 H8O MOL.WT .75.09Propyleneglycol is (RS)-propane-l,2-diol.

CATEGORY :

Pharmaceutical aid (humectant; solvent)

DESCRIPTION :

Clear, colourless, viscous liquid; practically odourless ; hygroscopic.

SOLUBILITY :

Miscible with water, with ethanol (95 %), with acetone and with chloroform.

Store in tightly-closed containers.

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RAW MATERIAL :PROPYLENEGLYCOL

PROTOCOL IP PAGE: 02 OF 04

STANDARDS:

IDENTIFICATION :

A. To 0.5 ml of a 0.01 % w/v solution , cooled in ice add 5 ml of a cooled mixture of10 ml of water and 90 ml of sulphuric acid. Heat for 10 minutes on a water bath at

70 deg, cool and add 0.2 ml of a 3 % w/v solution ninhydrin in a 2.5 % w/v

solution of sodium metabisulphite; a violet colour slowly appears.

B. Heat 0.15 ml with 0.1 g of boric acid; a pleasant odour develops.

C. Add 1 ml to 0.5 g of potassiumbisulphate and heat gently; a fruity odour develops

And when me solution is heated to dryness, no sharp, acrid smell ofacrolein isperceptible.

ACIDITY :

Mix 10 ml with 40 ml of water and add 0.1 ml ofbromothymol blue solution. The

solution is greenish yellow and not more than 0.05 ml of 0.1 M sodium hydroxide isrequired to change the colour to blue.

CLARITY AND COLOUR:

The substance being examined is clear. Appendix 6.1, and colourless,

Appendix 6.2.

BOILING RANGE :

Between 184 deg and 189 deg. Appendix 8.1

RELATIVE DENSITY:

Between 1.035 and 1.040, Appendix 8.15.

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PROTOCOL : IP PAGE: 03 OF 04

REFRACTIVE INDEX:

Between 1.431 and 1.433, Appendix 8.13.

HEAVY METALS:

Not more than 5ppm, determined by method D on 3 ml diluted to 12 ml with water.

Appendix 3.12. Use lead standard solution (IppmPb) to prepare me standard.

OXIDISING SUBSTANCES :

To 10 ml add 5 ml of water, 2 ml of potassium iodide solution and 2 ml of 1 M sulphuric

acid and allow to stand in a ground-glass-stoppered flask protected from light for 15

minutes. Titrate the liberated iodine with 0.05 M sodium tmosulphate using 1 ml of starchsolution , added towards the end of the titration, as an indicator. Not more than 0.2 ml of0.05 M sodium thiosulphate is required.

REDUCING SUBSTANCES :

Mix 1 ml with 1 ml of 6 M ammonia and heat in a water bath at 60 deg for 5 minutes; the

solution is not yellow. Immediately add 0.15 ml of 0.1 M silver nitrate; me solution doesnot change its appearance within 5 minutes.

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PROTOCOL : IP PAGE: 04 OF 04

OTHERGLYCOLS:Carry out the method for thin layerchromatography, Appendix 4.6, using silica gel G as

the coating substance and a freshly prepared mixture of 55 volumes of chloroform, 35

volumes of acetone and 10 volumes of efhanol (95 %) as the mobile phase. Applyseparately to the plate 5 ul of each of the following solutions.

Solution (1) is a 2.0 % w/v solution of the substance being examined. Solution (2)contains 0.02 % w/v each of diethylene glycol RS, ethylene glycol RS and propylene

glycol RS in ethanol (95 %). After removal of the plate, allow it to dry in air for 1 hour,

spray with a 0.1 % w/v solution of sodium metaperiodate and dry the plate in a current of

warm air. Spray with a solution prepared by dissolving 1.8 gm ofbenzidine in 50 ml ofethanol (95%) , adding 50 ml of water followed by 20 ml of acetone and 10 ml of 0.2 M

hydrochloric acid. Allow the plate to dry in air. Any secondary spot in the chromatogramobtained with the solution ( 1 ) is not more intense than any of the spots in the

chromatogram obtained with solution (2).

SULPHATED ASH :

Not more than 0.01 % w/w, determined by the following method. Heat 50 g until it bums,

and ignite. Allow to cool, moisten the residue with sulphuric acid and ignite; repeat theoperations.

WATER:

Not more than 0.2 % w/w, determined on 5 g, Appendix 3.24.

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TEST CERTIFICATE



Rawmaterial:Propyleneglycol IPParty : Universal Impex A.R.NO. :UIR 272/99-2000

G.R.N. No. :UI/RM/265/989 Pub. Lab. T.R.NO. :-

Batch No. : 11902071 Mfg. Date :Feb' 1999

Qty received : 3x215 kg. =645.0 kg. Exp. Date : -------

Manufacturer :SpicOrganics Dt of Receipt : 06/03/99

Supplier :Sneha Chemicals Dt of Completion : 07/03/99

Ch. No. /Dt : 1562 / 03-03-99 Qty sampled : 2 x 100 ml



Description Complies with IP Clear, colourless, viscous

liquid; practically odourlesshygroscopic.


Identification - A,B,C Complies with IP

Acidity Complies with IP

Clarity & colour of sol. Complies with IP

Boiling Range 187C 184C to 189 C

Relative Density 1.03820 1.035 to 1.040Refractive Density 1.431 1.431 to 1.433

Heavy metals Complies with IP

Oxidising Substances Complies with IP

Reducing substances Complies with IP

OtherGlycols Complies with IP

Sulphated ash 0.00145 %w/w NMT0.01% w/w

Water 0.14875% w/w NMT 0.2 %w/w

OPINION: In the opinion of the undersigned, the sample referred to above is of standard

quality as defined in the act and the rules thereunder with respect to the tests carried out

and mentioned above as perIP-96

Date : 07-03-99 Analy Q.C.Incharge:

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RAW MATERIAL : POTASSIUM HYDROXIDE

PROTOCOL : IP-1966 PAGE : 01 OF 02

KOH 56.11

Caustic Potash.

STANDARDS:

Potassium hydroxide contains not less than 85 % of total alkali, calculated as KOH and

not more man 4.0 per cent of K2CO3.

DESCRIPTION:

Dry, white sticks,pellets or fused mass; hard, brittle and showing a crystalline fracture.

Very deliquescent. Strongly alkaline and corrosive.

SOLUBILITY:

Soluble in 1 part of water, in 3 parts of alcohol (90%), and in about 2.5 parts of glycerin;very soluble in boiling ethyl alcohol.

IDENTIFICATION :

Gives the reactions characteristic of potassium, page 928.

ALUMINIUM, IRON, AND MATTER INSOLUBLE IN HCL:

Boil 5 g with 40 ml of dilute HCL , cool, make alkaline with dilute ammonia solution,boil, filter, and wash athe residue with 2.5 per cent w/v solution of ammonium nitrate; the

insoluble residue, after ignition to constant weight, weighs not more than 5 mg.

ARSENIC :

Not more than 4ppm, page 971

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RAW MATERIAL : POTASSIUM HYDROXIDE


CHLORIDE:0.5 g dissolved in water with the addition of 1.6 ml of nitric acid, complies with the limit

test for chlorides, page 930.

HEAVY METALS:

Dissolve 1 g in a mixture of 5 ml of water and 7 ml of dilute HCL. Heat to boiling, add 1

drop ofphenolpthalein solution and dilute ammonia solution dropwise to produce a faintpink colour. Add 2 ml of acetic acid and water to make 25 ml; the limit of heavy metals is

30ppm, page 931.

SULPHATE:

Dissolve 1 g in water with the addition of 4.5 ml of hydrochloric acid; the solutioncomplies with limit test for sulphates, page 931.

SODIUM :

To 3 ml of a 10 per cent w/v solution add 1 ml of water, 1.5 ml of alcohol, and 3 ml of

potassium antimonate solution and allow to stand; no white crystalline precipitate or

sediment is visible to the naked eye within fifteen minutes

ASSAY:

Weigh accurately about 2 g, and dissolve in 25 ml of water, add 5 ml of barium chloride

solution, and titrate with 1 N hydrochloric acid, using phenolphfhalein solution as

indicator. To the solution in me flask add bromophenol blue solution, and continue the

titration with 1 N hydrochloric acid. Each ml of 1 N hydrochloric acid, used in the secondtitration is equivalent to 0.06911 g of K2C03. Each ml of 1 N hydrochloric acid, used

in the combined titration is equivalent to 0.05611 g of total alkali, calculated as KOH.

STORAGE:

KOH should be kept in a well closed container.

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TEST CERTIFICATE



RAW MATERIAL : POTASSIUM HYDROXIDE IPParty : Universal Impex A.R.NO. : UIR 141/98-99

G.R.N. No. :UI/RM/ Pub. Lab. T.R.NO. :-

Batch No, : - Mfg.Date:-

Qty received : lx50kg.-50.0kg. Exp. Date : -

Manufacturer : The National Che.Cor Dt of Receipt : 02/09/98

Supplier : Dt of Completion : 06/09/98

Ch.No./Dt : 0037 / 98-99 Qty sampled : 2 x 20 g



Description Complies with IP Dry, white pellets or fused

mass; hard brittle and showingcrystalline fracture; very

deliquescent; strongly alkaline

& corrosive.


Identification Complies with IP

Aluminium, Iron &

matter insoluble in HC1

Complies with IP NMT: 5 mg

Arsenic Complies with IP NMT4PPM

Chloride Complies with IP

Heavy metals Complies with IP NMT 30 PPM

Sulphate Complies with IP

Sodium Complies with IP

Assay as KOHK2C03 85.486 % 1.394 % NLT 85.0 % NMT 4.0%

OPINION: In the opinion of the undersigned, the sample referred to above is of standardquality as defined in the act and the rules thereunder with respect to the tests carried out

and mentioned above as per IP-66

Date : 06-09-98 Anatyst Q.C.Incharge.

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RAW MATERIAL :DISODIUM EDETATE


CioH14N2Na2O8,2H2O Mol.Wt. 372.24

Disodium Edetate is disodiumethylenediaminetetra acetate dihydrate.

CATEGORY:

Pharmaceutical aid; dictating agent in metal poisoning.

DOSE :

By intravenous injection, 50 mg per kg of body weight, upto a maximum of

3 g per day.

DESCRIPTION:White, crystalline powder; odourless.

SOLUBILITY:

Soluble in water, sparingly soluble in ethanol (95%); practically insoluble in

chloroform and in ether.

STANDARD:

Disodium Edetate contains not less than 98.5 % and not more than 101.0per cent of CioHi4N2Na208,2H20.

IDENTIFICATION :

A. The infra-red absorption spectrum. Appendix 5.4, is concordant with the reference

spectrum of disodium edetate or with the spectrum obtained from disodium

edetate RS.

B. Dissolve 2 g in 25 ml of water, add 6 ml of lead nitrate solution, shake and add 3

ml of potassium iodide solution; no yellow precipitate is produced. Make alkalineto red litmus paper with 2 M ammonia and add 5 ml of ammonium oxalate

solution ; nopreciptate is produced.

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RAW MATERIAL :DISODIUMEDETATE

PROTOCOL : IP 1996 PAGE: 01 OF 02

C. Dissolve 0.5 g in 10 ml of water, add 0.5 ml of a 10 % w/v solution of calcium

chloride, make alkaline to red litmus paper with 2 M ammonia and 3 ml ofammonium oxalate solution ; no precipitate is produced.

D. Gives the reaction of sodium salts. Appendix 3.1.

pH:

Between 4.0 and 5.5, determined in a 5 % w/v solution. Appendix 8.11.


A 5.0 % w/v solution in carbondioxide-free water is clear. Appendix 6.1, and colourless.

Appendix 6.2.

HEAVY METALS:

Not more than 20ppm, determined on 1.0 g by Method A, Appendix 3.12.Use 2 ml of lead standard solution (10 ppm Pb) to prepare the standard.

IRON:

10ml of a2.5% w/v solution complies with the limit test for iron, Appendix 3.13 (80ppm). Add 0.25 g of calcium chloride to each solution before adding mercaptoacetic acid.

ASSAY:

Weigh accurately about 0.5 g, dissolve in sufficient water to produce 300 ml and add 2 gofhexamine and 2 ml of 2M hydrochloric acid. Titrate with 0.1 M lead nitrate using about50 mg ofxylenol orange triturate as indicator. Each ml of 0.1 M lead nitrate is equivalent

to 0.03722 g of CioH14N2Na2O8,2H2O.

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TEST CERTIFICATE



RAW MATERIAL :DISODIUMEDETATE IPParty : Universal Impex A.R.NO. : UIR 6/96-97

G.R.N. No. : UI/RM/ Pub. Lab. T.R.NO. : 0/A8888

Batch No. : 0116 Mfg. Date ; July 96

Qty received : 1x5 kg. =5.0 kg. Exp. Date :.

Manufacturer: Alliance DyechemP.L Dt of Receipt : 22/03/97

Supplier Smeeta traders Dt of Completion : 28/03/97

Ch.No./Dt: 345/ 22-3-97 Qty sampled : 2x25g

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS PER IP -96.

.


Description Complies with IP White, crystalline

powder; odourless


Identification A,B,C,& D Complies with IP

PH 4.59 Bet. 4.0 and 5.5

Clarity and colour of sol Complies with IP

Heavy metals Complies with IP NMT 20 PPM

Iron 0.05989 % NMT80PPM

Assay C10H14N2Na208,2H2O 100.665 % Bet. 98.5% and 101.0%

OPINION : In the opinion of the undersigned, the sample referred to above is of

standard quality as defined in the act & the rules thereunder with respect to the testscarried out & mentioned above asperJP96specifiction

Date : 28/03/97 Analyst Q.C. Incharge

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RAW MATERIAL :METHYLPARABEN

PROTOCOL : IP-1996 PAGE: 01 OF 03

C8H8O3 Mol.Wt.l52.15

Methyl Hydroxybenzoate

Methylparaben is methyl 4- hydroxybenzoate.

CATEGORY:

Pharmaceutical aid (antimicrobial preservative)

DESCRIPTION :

Colourless crystals or white, crystalline powder.

SOLUBILITY:Freely soluble in ethanol (95%), in ether and in methanol; very slightly in

water.

STORAGE:

Store in well closed containers.

STANDARDS

Methylparaben contains not less than 99.0 per cent and not more than 101.0 per cent of

C8H8O3.

IDENTIFICATION :

Test A may be omitted if test B,C, D and E are carried out. Tests B,C and D may be

omitted if test A and E are carried out.

A. The infra-red absorption spectrum. Appendix 5.4, is concordant with the referencespectrum ofmethylparaben or with the spectrum obtained from methylparaben

RS.

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B. The light absorption in the range 230 to 360 nm of a 0.0005% w/v in ethanol

(95%) exhibits a maximum at about 258 nm; absorbance at about 258 nm, 0.52 to0.56, Appendix 5.5.

C. Boil 10 mg with 10 ml of water, cool and add 0.05 ml of ferric chloride solution;a reddish violet colour is produced.

D. Dissolve 0.1 g in 2 ml of ethanol (95%), boil and add 0.5 ml ofmercuric nitrate

solution; a precipitate is formed and the supernatant liquid becomes red.

E. Melts between 125 and 128, Appendix 8.8.

ACIDITY:Dissolve 1.0 g in sufficient ethanol (95%) to produce 10 ml. To 2 ml of the solution add 3

ml of ethanol (95%), 5 ml of carbon dioxide-free water and 0.1 ml ofbromocresol greensolution. Not more than 0.1 ml of 0.1 M sodium hydroxide is required to change the

colour of solution.


A 10 % w/v solution in ethanol (95%) is clear. Appendix 6.1, and not more intensely

coloured than reference solution BYS6, Appendix 6.2.

CHLORIDE:

Heat 2 g with 100 ml of water, cool, add sufficient water to restore the original volume,and filter. 25 ml of the filtrate complies with the limit test for chlorides. Appendix 3.10(500ppm).

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SULPHATE:

To 10 ml of the filtrate obtained in the test for chloride add 0.15 ml of dilute hydrochloricacid and 0.1 ml of barium chloride solution; no turbity is produced within 10 minutes.

RELATED SUBSTANCES:

Carry out the method for thin-layer chromatography. Appendix 4.6, using silica gel

HF254 as the coating substance and a mixture of 88 volumes of dichlormethane, 10

volumes of ethyl acetate and 2 volumes of anhydrous formic acid as the mobile phase.

Apply separately to the plate 5 ul of each of two solutions of me substance beingexamined in methanol containing (1) 2.0 % w/v and (2) 0.02 % w/v respectively. After

removal of the plate, dry it in a current of hot air and examine under ultra-violet light

(254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not

more intense than me spot in the chromatogram obtained with solution (2).

SULPHATED ASH:

Not more than 0.1%, Appendix 3.22.

ASSAY:

Weigh accurately about 80 mg, transfer to a glass-stoppered flask, add 25 ml of 2 Msodium hydroxide and boil gently under reflux condenser for 30 minutes. Cool and add

25.0 ml of 0.0333 M potassium bromate, 5 ml of a 12.5 % w/v solution of potassium

bromide and 40 ml of glacial acetic acid, cool in ice, add 10 ml of hydrochloric acid,immediately stopper the flask and allow to stand for 15 minutes. Add 15 ml of potassium

iodide solution, mix and titrate athe liberated iodine with 0.1 M sodium thiosulphateusing 2 ml of starch solution, added towards the end of the titration, as indicator.Repeat the operation without the substance being examined. The difference between the

titrations represents the amount of potassium bromate required. The volume of 0.0333 M

potassium bromate is equivalent to half of the volume of 0.1 M sodium thiosulphate

required for the titration. Each ml of 0.0333 M potassium bromate is equivalent to0.005072 g ofC8H8O3.

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TEST CERTIFICATE



RAW MATERIAL : METHYL PARABEN IPParty : Universal Impex A.R.NO. : UIR 173/98-99

G.R.N. No. :UI/RM/167/989 Pub. Lab. T.R.NO

Batch No. :M/098/998 Mfg. Date ; Sep'1998Qty received : 1x10 kg. =10.0 kg. Exp. Date Aug' 2003

Manufacturer :Salicylates & Chemical Dt of Receipt 17/10/98

Supplier :Harish Enterprises Dt of Completion : 31/10/98

Ch. No. /Dt : 899 / 14-10-98 Qty sampled '2x20g

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS PER IP -96

Protocols Results Claim / LimitDescription Complies with IP White, crystalline

powder; odourless.


Identification A,B,C,D & E Complies with IP C.

0.542 E. 126

C. 0.52 to 0.56 E.

125to 128



Chloride Complies with IP NMT 500 PPM


Related substances Complies with IP

Sulphated ash 0.03989 % NMT 0.1 %Assay as C8H8O3. 100.068 % Bet. 99.0% & 101.0%

OPINION: In the opinion of the undersigned, the sample referred to above

is of standard quality- as defined in the act & the rules thereunder with

respect to the tests carried put & mentioned above as get IP-96 specification

Date : 31/10/98 Analyst Q.C.Incharge

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RAW MATERIAL :PROPYLPARABEN


C10H12O3 Mol.Wt. 180.20

PropyiHydroxybenzoate

Propyiparaben ispropyi 4- hydroxybenzoate.

CATEGORY:

Pharmaceutical aid (antimicrobial preservative)

DESCRIPTION :

Colourless crystals or white, crystalline powder.

SOLUBILITY:

Freely soluble in ethanol (95%), in acetone, in ether and in methanol; very slightly inwater.

STORAGE:

Store in well closed containers.

STANDARDS

Propylparaben contains not less than 99.0 per cent and not more than 101.0 per cent of

C10H12O3, calculated with reference to the dried substance.

IDENTIFICATION:

A. The light absorption in the range 230 to 360 nm of a 0.0005% w/v in ethanol (95%)exhibits a maximum at about 258 nm; absorbance at about 258 nm, 0.44 to 0.47,Appendix 5.5.

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B. To about 10 mg in a test tube add 1 ml of sodium carbonate solution, heat it to

boiling for 30 seconds and cool (solution A). To a further 10 mg in a test tube add1 ml of sodium carbonate solution; the substance partly dissolves (solution B).

Add at the same time to each of solution A and B 5 ml of aminophenazone

solution and 1 ml of potassium ferricyanide solution and mix. Solution B isyellow to orange - brown. Solution A is orange to red and the colour is clearly

more intense than any similar colour that may obtained with solution B.

C. Melts between 96 and 99, Appendix 8.8.


A 10 % w/v solution in ethanol (95%) is clear. Appendix 6.1, and not more intenselycoloured than reference solution BYS6, Appendix 6.2.

ACIDITY :

Dissolve 1.0 g in sufficient ethanol (95%) to produce 10 ml. To 2 ml of the solution add 3

ml of ethanol (95%), 5 ml of carbon dioxide-free water and 0.1 ml ofbromocresol green

solution. Not more than 0.1 ml of 0.1 M sodium hydroxide is required to change thecolour of solution.

CHLORIDE:

Heat 2 g with 100 ml of water, cool, add sufficient water to restore the original volume,

and filter. 25 ml of the filtrate complies with the limit test for chlorides. Appendix 3.10(500ppm).

SULPHATE:

To 10 ml of the filtrate obtained in the test for chloride add 0.15 ml of dilute hydrochloric

acid and 0.1 ml of barium chloride solution; no turbity is produced within 10 minutes.

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PROTOCOL : IP 1996 PAGE: 03 OF 03

RELATED SUBSTANCES :

Carry out the method for thin-layer chromatography. Appendix 4.6, using silica gelHF254 as the coating substance and a mixture of 88 volumes of dichlormethane, 10

volumes of ethyl acetate and 2 volumes of anhydrous formic acid as the mobile phase.

Apply separately to the plate 5 ul of each of two solutions of the substance beingexamined in methanol containing (1) 2.0 % w/v and (2) 0.02 % w/v respectively. After

removal of the plate, dry it in a current of hot air and examine under ultra-violet light

(254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not

more intense than the spot in the chromatogram obtained with solution (2).

SULPHATED ASH:

Not more man 0.1%, Appendix 3.22.

LOSS ON DRYING:

Not more than 0.5 %, determined on 1 g by drying over silica gel for 5 hours . Appendix8.6.

ASSAY:

Weigh accurately about 80 mg, transfer to a glass-stoppered flask, add 25 ml of 2 Msodium hydroxide and boil gently under reflux condenser for 30 minutes. Cool and add

25.0 ml of 0.0333 M potassium bromate, 5 ml of a 12.5 % w/v solution of potassium

bromide and 40 ml of glacial acetic acid, cool in ice, add 10 ml of hydrochloric acid,immediately stopper the flask and allow to stand for 15 minutes. Add 15 ml of potassium

iodide solution, mix and titrate athe liberated iodine with 0.1 M sodium thiosulphateusing 2 ml of starch solution, added towards the end of the titration, as indicator.

Repeat the operation without the substance being examined. The difference between the

titrations represents the amount of potassium bromate required. The volume of 0.0333 M

potassium bromate is equivalent to half of the volume of 0.1 M sodium thiosulphaterequired for me titration. Each ml of 0.0333 M potassium bromate is equivalent to

0.006007 g ofC10H12O3.

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TEST CERTIFICATE



RAW MATERIAL : PROPYL PARABEN IP

Party : Universal Impex A.R.NO. : UIR 98/98-99G.R.N. No. : UI/RM/ Pub.Lab.TR.NO :

Batch No. : P/015/698 Mfg. Date : June' 1998

Qty received : 1 x 10 kg. = 10.0 kg. Exp. Date : May'2003

Manufacturer : Salicylates & Chemical Dt of Receipt : 27/07/98

Supplier : Harish Enterprises Dt of Completion : 29/07/98

Ch. No. / Dt : 492/21-07-98 Qty sampled : 2xl0g

RESULTS OF ANALYSIS & PROTOCOLS OF TEST APPLIED AS PER IP -96.


Description Complies with IP White, crystalline powder;

odourless.


Identification A,B,C Complies with IP A- 0.44 to 0.47 E. 96to 99

A- 0.452 C- 97



Chloride Complies with IP NMT500PPM


Related substances Complies with IP

Sulphated ash 0.04% NMT 0.1 %

Loss on drying 0.44% NMT0.5%

Assay as C8H8O3. 100.07% Bet. 99.0%& 101.0%

OPINION: In the opinion ofthe undersigned, the sample referred to above

is of standard quality' as defined in me act & the rules thereunder withrespect to the tests carried out & mentioned above as per IP96 specifiction

Date : 29/07/98 Analyst Q.C.Incharge

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RAW MATERIAL : PURIFIED WATER IP

PROTOCOL : IP 1996 PAGE:01 OF 03

H2O Mol.Wt. 18.02

Purified water is prepared by distillation by means of ion exchange or by any other appropriate

means from suitable potable water mat complies with allrelevant statutory regulations.

CATEGORY:

Pharmaceutical aid (solvent)

DESCRIPTION :

Clear, colourless liquid; odourless and tasteless.

STORAGE:

Store in well closed containers of a material that does not alter the properties

of the water.

STANDARD:

ACIDITY OR ALKALINITY:

To 10 ml, freshly boiled and cooled in a borosuicate glass flask, add 0.05 mlof methyl red solution; me resulting solution is not red. To 10 ml add 0.1 ml

ofbromothymol blue solution; the resulting solution is not blue.

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AMMONIUM :

To 20 ml add 1 ml of alkaline potassium mercuri-iodide solution and allow

to stand for 5 minutes. When viewed vertically the solution is not moreintensely coloured than a solution prepared at the same time by adding 1 ml

of alkaline potassium mercuri-iodide solution to a solution containing 2.5

ml of dilute ammonium chloride solution and 7.5 ml of the liquid being

examined.

CALCIUM AND MAGNESIUM:

To 100 ml add 2 ml of ammonia buffer pH 10.0, 50 mg of mordant black IImixture and 0.5 ml of 0.01 M disodium edetate; a purple blue colour is

produced.

HEAVY METALS:

Not more than 0.1 ppm, determined by Method D on 12 ml of a solutionprepared in the following manner. In a glass evaporating dish evaporate 150

ml to 15 ml on a water bath. Use lead standard solution (1 ppm Pb) to

prepare the standard , Appendix 3.12.

CHLORIDE:

To 10 ml add 1 ml of 2 M nitric acid and 0.2 ml of 0.1 M silver nitrate; the

appearance of the solution does not change for at least 15 minutes.

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PROTOCOL IP - 1996 PAGE: 03 OF 03

NITRATE :

To 5 ml in a test-tube immersed in ice add 0.4 ml of 10 % w/v solution of

potassium chloride, 0.1 ml of diphenylamine solution and, dropwise withshaking, 5 ml of sulphuric acid. Transfer the tube to a water-bath at 50 and

allow to stand for 15 minutes. Any blue colour in the solution is not more

intense than that in a solution prepared at the same time and in the same

manner using a mixture of 4.5 ml of nitrate-free water and 0.5 ml of nitratestandard solution (2 ppm N03) (0.2 ppm).

SULPHATE:

To 10 ml add 0.1 ml of 2 M hydrochloric acid and 0.1 ml of barium chloride

solution. The appearance of the solution does not change for at least 1 hour.

OXIDISABLE SUBSTANCES:

To 100 ml add 10 ml of 1 M sulphuric acid and 0.1 ml of 0.02 M potassiumpermanganate and boil for 5 minutes ; the solution remains faintly pink.

RESIDUE ON EVAPORATION:

Evaporate 100 ml to dryness on a water-bath and dry to constant weight at105. The residue weighs not more than 1 mg (0.001 %).

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TEST CERTIFICATE




Party : UniversalImpex A.R.NO. : PWR 12/97-98

Batch No. : 12/98-99 Dt of Completion : 16/05/99

Qty sampled : Hit. Dt of Completion : 16/05/99



Description Complies with IP Clear colourless liquid;

odouless and tasteless.Acidity or alkalinity Complies with IP

Ammonium Complies with IP

Calcium & magnesium Complies with IP

Heavy metals Complies with IP NMT 0-1 ppm

Chloride Complies with IP

Nitrate Complies with IP NMT 0.2 ppm


Oxidisable matter Complies with IP NMT 0.001%

Residue on evaporation Complies with IP

OPINION : In the opinion of the undersigned, the sample referred to above

is of standard quality as defined in the act and the rules thereunder with

respect to the tests carried out and mentioned above as per IP specifications.

Date : 16/05/98 Analyst Q.C. Incharge

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SECTION IV

DETAILS OF SPECIFICATIONS AND STANDARDS

LAID DOWN BY THE MANUFACTURER FOR

EACH PRODUCT TOGETHER WITH ITS METHOD

OF ANALYSIS

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RAW MATERIAL REQUISITION

PRODUCT :ROXICAMGEL UNIVERSAL IMPEX

89,PeerbhoyBldg.,

Mumbai-400002 India

MFC.NO. :MF/UI-02

BATCH NO. : 01 SR. N0 :23

BATCH SIZE : 300 KGS PACK SIZE :30GMMFG.DATE: APR. 1999 DT. OF STARTING : 22/4/99

EXP.DATE:MAR.2001 DT OF COMPLETION : 27/4/99

No INGREDIENTS SPEC LABEL

CLAIM %

w/w

OVER

AGES

% w/w

A.R NO. UIR QTY IN KGS

THEOR.

ACTUAL

WT.

BY

CH

K

BY

1 Piroxicam IP 0.50% 5.0 257/98-99

8/99-2000

1.575 1,575

2 Carbomer934 USP 0.90 % - 287/98-99 2.700 2.700

3 Glycerin IP 10.00% - 228/98-99 30.000 30.000

4 Propyleneglycol IP 20.00% 272/98-99 60.000 60.000

5 Potassium Hydroxide IP 0.80% 141/98-99 2.400 2.400

6 DisodiumEdetate IP 0.01% - 6/96-97 0.030 0.030

7 Methyl Paraben IP 0.16% 173/98-99 0.480 0,480

8 Propyi Paraben IP 0.04% 98/98-99 0.120 0.120

9 D.M.WaterQ.S.to IP 300.00 300.00

0

STORES INCHARGE PRODUCTION INCHARGE QUALITY CONTROLINCHARGE

A. .

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LIST OF VESSELS AND EQUIPMENT USED

SR. NO. DESCRIPTION MAKE CAPACITY

1 Main mixing vessel Aerolite Industries 300 Kgs2 Mechanical Sifter Smitact Equipments

3 Colloid Mul Clit Industries

4 Homogenisor Remi Industries 1400 rpm

5 S.S. Storage vessels S.S Mechanical Works 200 Kgs

6 Filling Machine Precitech Industries 25000 tubes per shift

A.........

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MANUFACTURING PROCESS

PRODUCT :ROXICAM GEL BATCH NO. : 01BATCH SIZE : 300 KGS PAGE : 01 OF 03

A. Cleaning & General Instructions

Ensure the following before commencing the production.

1. The floor and ceilings of the area should be thoroughly cleaned and should not

contain any foreign material attached to it.

2. All equipments are cleaned and washed thoroughly. No material of previously runmaterial should stick to these. When machine is ready for use, approval should be

obtained from Quality Control Department after checking the wash water content.

3. The raw materials required must be previously checked for labels and weight.

4. Proper temperature records should be maintained throughout me processing as perthe instructions.

5. Equipments and containers should be labelled at each and every stage ofmanufacturing.

6. All processing should be carried out under strict supervision of a QualifiedCompetent staff.

7. Production personnel should wear gloves and masks before they enter the

manufacturing area while handling the material.

A.........

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MANUFACTURING PROCESS

PRODUCT :ROXICAM GEL BATCH NO. : 01

BATCH SIZE : 300 KGS PAGE : 02 OF 03

A. PREPARATION OF CARBOMERGEL.

Main Mixing Vessel cleaned by : ____________

Homogenisercleaned by : _____________

Checked by : ________________

STEP I TransferPropyleneGlycol( 59.000 Kgs), Glycerin ( 30.000

Kgs ) in ajacketted main mixing tank and start heating. Holdtemperature around 55 C to 60 C. Add carbomer-934 ( 2.700 Kgs )

slowly with constant high speed stirring to form a uniform gel. Continuestirring for 15-20 minutes and allow to stand over night.

Temp. of water: __________ Checked By; ___________

Note : Add Carbomer-934 into the vortex caused by high speed stirring.

STEP II Transfer 180 litres ofD.M water into the main mixing tank.

Add disodiumEdetate. Start heating and hold temp. around 50 -55 C.Temp. of water phase :- 55C Checked By:- __________

STEP IIITransfer 90 Lit of D.M. Water from STEP II to STEP Iunder high speed stirring. Continue stirring for 20-30 min.

STEP IV In a separate container dissolve Methyl Paraben (0.480 Kgs)Propyiparaben (0.120 kgs) inpropylene Glycol (1.00 Kg) by heating, till

solution is clear. Add the clear solution to STEP I.

Checked by :-

A.........

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PRODUCT :ROXICAM GEL BATCH NO. : 01

BATCH SIZE : 300 KGS PAGE : 03 OF 03

STEP V Add and dissolve potassium Hydroxide pellets (1.900 Kgs)

in 6.0 litres ofD.M. water. Filter and add to STEP I.

STEP VI Transfer the contents of the S.S vessel from STEP I onto

the main mixing tank under constant stirring and continue stirring for 30min. Start cooling. CheckpH (Range 7.0 to 8.0)

B. DISSOLUTION AND ADDITION OF PIROXICAM:

Add and dissolve potassium hydroxide (0.500 Kgs) in 6.00 kgs of D.M.water. Add Piroxicam (1.575 kgs). Stir well to get a clear solution. Filter

and add to the main mixing tank and mix for about 20 minutes. Check

pH (range 7.0 to 8.0). Make up the volume of the bulk, by addition of

remaining D.M.water(about 11 .00 kgs)>

C. UNLOADING:

1. Transfer the bulk in the S.S. Storage vessel with proper label.

2. Check for the theoretical yield : _________

3. Manufacturing Chemist : _____________

4. Manufacturing operator :_____________

5. Manufacturing started on : Date :______ Time:___________

6. Manufacturing completed on : Date : _________ Time : _________7. Inform Q.C. to draw Sample .

A.........

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FILLING PROCESS

A. FILLING INSTRUCTION:

1. Assemble the filling machine as per instruction.

2. After getting the approval from Quality Control Department take the cream forfilling,

3. A required information should be sent to Quality Control Department

immediately after the commencement of the filling.

4. Adjust the filling machine to get the desired weight.5. Only one product is to be filled at a time.

6. Single batch should start and finish at a time.

B. FILLING IN-PROCESS :

1. Check for parameters such as crimping, coding, leakage ,Wt. Variation.2. A filling chart should be maintained during the filling of the batch.

3. All the crates and machines should be labelled property indicating the product

name. Batch No., Quantity processing stage. Date and initials of the supervisingauthority.

4. After the completion of filling or during online, the intimation should be given the

packing department for packing.

5. All filled tubes should be transferred to the Packaging Department alongwith metransfer slip and complete records

A.........

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PACKING PROCESS

A. PRIMARY PACKING :

1. The tube is packed in the carton from right hand side.

2. The carton is unfolded and sealed from left hand side by the flaps. The tube iscarefully put in the carton by right hand holding the carton in the left hand. The

side on which details ofMfg. Lie., No., Batch No.,Mfg. Date, Exp. Date & Retail

price are given should be treated as a front side. Finally the right hand side flaps

on me carton should be folded and sealed. The carton should be placed withinside tube in upright position.

B. SECONDARY PACKING :

1. The outer cartons should be overprinted with Mfg. Lie. No., Batch No. Mfg.

Date., Exp Date & Retail price.

2. FOR 30 G: Twenty carton boxes are placed in 5 rows , 4 in each row.

The rows are placed vertically one after the another. Finally the opening flap isclosed.

C. TERTIARY PACKING:

1. The master shipper is formed with upper lids opened and the lower lids sealed by

3 inch BOPP tapes

2. For 30 g :- The secondary outer are placed in two rows one above the another.

One row consists of 5 x 2 outer. Thus 20 such outer are packed in one shipper.

3. Finally the master shipper is sealed by 3 inch BOPP tape with H type sealing to

cover all end. An overprinted label with Product Name, Batch No., Mfg. Date,

Exp. Date & Packing is pasted in the middle of the master shipper.

A........

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ANALYTICAL CHECKS PERFORMED DURING FILLING AND

PACKING PROCESS

SR.NO. CHECKS DURATION1 Average weight After every 30 min

2 Individual weight After every 60 min

3 Coding After every 30 min

4 Crimping After every 30 min

5 Leak test After every 30 min

6 Carton/Outer overprinting After every 30 min

7 Shipper packing After every 30 min

8 Labelling Each & every shipper

THEORETICAL YIELD

PROCESS MINIMUM

Mixing 99.00

Filling 98.50

Packaging 98.00

RESPONSIBILITY

1 Production Mfg. Chemist/Operators

2 In-Process Quality Control Quality Control Chemist

A .

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FINISHED PRODUCT :

PROTOCOL :INHOUSE PAGE: 01 OF 02

FINISHED PRODUCTS SPECIFICATIONS, STANDARDS &

ANALYTICAL CONTROL LIMITS

DESCRIPTION:

Yellow coloured homogeneous transparent gel.

IDENTIFICATION:

pH: 7.0 to 8.0Determine directly on the cream using a suitable calibrated pH meter.

LEAICTEST:

Limit: No leakage is observed in any of the 10 tubes tested.

Select 10 tubes of the gel with seal applied thoroughly. Clean and dry the exteriorsurfaces of the tube with absorbent cloth. Place the tubes in a horizontal position on a

sheet of filter in an oven maintained at 45C 3C for 8 hours. No significant leakages

occur during or at the completion of the test in all samples .( Disregard traces of creamnear the crimp or thread of the cap.

MINIMUM FILL TEST:

The average net weight of the content of the 10 tubes is not less than 15 g and the net

weight of content of any of the tube is between 15.0 to 15.5 g. Select a sample of 10 filled

tubes and remove any labelling. Thoroughly clean and dry the outside of the tubes bysuitable means and weigh individually. Quantitatively remove the content of each tube by

cutting it open and washing with a suitable solvent, if necessary taking care to retain

the closure and other parts of each tube. Dry and reweigh each empty tube along with itscorresponding parts. Difference between the two weights is the net weight of the content

of the tube. The average net weight of the content of the 10 tubes is not less than labelled

amount.

A.........

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FINISHED PRODUCT : ROXICAM GEL

PROTOCOL :INHOUSE PAGE : 02 OF 02

ASSAY:

The method is based on differential spectroscopy.

REAGENTS :

1. 0.01N methanolic hydrochloric acid.

2. 0.01 N methanolic sodium hydroxide

STANDARD SOLUTION:

10 mcg/ml ofpiroxicam in 0.01 methanolic hydrochloric acid and methanolic sodium

hydroxide.

SAMPLE SOLUTION :

Accurately weighed quantity of the sample equivalent to 10 mg of the substance wasextracted with methanol to get solution of 100 mcg/ml. Further dilution were done as

given under standard solution.

PROCEDURE :Measure the absorbance of acidic solution of both sample and standard at 326 nm using

respective alkaline solution as blank and calculate the result by comparision. The method

obeys Beer's law in the concentration range of 4-22 mcg/ml

A.........

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SECTION V

CERTIFICATE OF STERILITY AND ABSENCE OF

PROGEN : WHEREVER IT IS APPLICABLE

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SECTION VI

SAMPLES OF THE PRODUCT APPLIED FOR

REGISTRATION IN THEIR ORIGINAL PACK

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SPECIFICATIONS OF THE PACKAGING MATERIAL

A. PRIMARY PACKING:

The tube is packed in the carton from right hand side.

The carton is unfolded and sealed from left hand side by the flaps. The tube is

carefully put in the carton by right hand holding the carton in the left hand. The

side on which details ofMfg. Lie., No., Batch No.,Mfg . Date, Exp. Date & Retailprice are given should be treated as a front side. Finally the right hand side flaps

on the carton should be folded and sealed. The carton should be placed with

inside tube in upright position.

B SECONDARY PACKING:

The outer cartons should be overprinted with Mfg. Lie. No., Batch No.Mfg. Date., Exp Date & Retail price.

FOR 30 G: Twenty carton boxes are placed in 5 rows , 4 in each row.The rows are placed vertically one after the another. Finally the opening flap is

closed.

C. TERTIARY PACKING:

The master shipper is formed with upper lids opened and the lower lids sealed by3 inch BOPP tapes

For 30 g :- The secondary outer are placed in two rows one above the another.

One row consists of 5 x 2 outer. Thus 20 such outer are packed in one shipper.

Finally the master shipper is sealed by 3 inch BOPP tape with H type sealing to

cover all end. An overprinted label with Product Name, Batch No., Mfg. Date,Exp. Date & Packing is pasted in the middle of the master shipper.

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SPECIFICATION FOR PACKING MATERIAL

TUBES 30 G

1 Description Three colour tube , with proper impression of logo and

readable printing in English language as per the artwork. (* The colour of the tube should match with the

standard colour of the carton.

2 Length upto Shoulder 120.0mm (lmm)

3 Shoulder diameter 22.0 mm ( 1 mm )

4 Length upto cap 137.0mm (lmm)

5 Weight of empty tube 5.0 g( .250 g)

6 Lacquering Should be complied as per IS specification

7 Porosity Should be complied as per IS specification

CARTONS 30 G

1 Description Three colour carton made out of 300 gsm Board, with

proper impression of logo and readable Printing in Englishlanguage as per the art work. (* The colour of the carton

should match with the standard colour of the tube.

2 Design Both side open

3 Length 145.0mm ( 1 mm)

4 Height 32.0mm (lmm)5 Width 24.0 mm ( 1 mm)

6 Grammage 300 gsm ( 5 gsm )

A.

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SPECIFICATION FOR PACKING MATERIAL

OUTERS FOR 30 G

1 Description Three colour Outer made out of 350 gsm Board , withproper impression of logo and readable printing in English

language as per the art work. (* The colour of the outershould match with the standard colour of the tube & carton.

2 Design One side open

3 Length 165.0mm ( 1 mm )

4 Height 151.0mm (lmm)

5 Width 105.0mm (lmm)

6 Grammage Not less than 350 gsm

5 PLY SHIPPERS FOR 30 G

1 Description Five ply Master Shipper of 115 gsm each sheet.

2 Design Both side open

3 Length 54.0cm (0.5 cm)

4 Height 38.5cm (0.5 cm)

5 Width 38.5cm (0.5 cm)

6 Grammage Not less man 575 gsm

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SECTION - VII

CERTIFICATE OF ANALYSIS

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TEST CERTIFICATE



Party : Universal Impex A.R.NO. :UIF 17/99-2000

Product :Roxicam gel Dt of the Receipt : 24/04/99Batch No. : 01 Dt of the Completion : 27/04/99

Batch Size : 300 kgs Public lab T.R. No. :0/C 11828

Mfg. Date :Apr'1999 Qty drawn for sampling : 15x30g

Exp. Date : Mar'2001 Packing details : 9878x 15g

RESULTS OF ANALYSIS AND PROTOCOLS OF TEST APPLIED

AS PERINHOUSE SPECIFICATION.

A Pale yellow coloured homogenous gel.

1. DESCRIPTION : A Pale yellow coloured homogenous gel.2. IDENTIFICATION : Positive for Piroxicam.

3. pH at 40C : 7.47 Limit 7.00 to 8.004. LEAK TEST : Complies

5. MINIMUM FILL TEST : Complies

No Wt of

FilledTube in

g

Wt of

EmptyTube in

g

Wt of net

Content ofTube in

g

Sr

No

Wt of

FilledTube in

g

Wt of

EmptyTube in

g

Wt of net

Content ofTube in

G

1 35.3890 5.3856 30.0034 6 35.4427 5.4384 30.0043

2 35.4701 5.4627 30.0074 7 35.4331 5.4255 30.00763 35.3849 5.3782 30.0067 8 35.5395 5.5347 30.0048

4 35.3564 5.3479 30.0085 9 35.5766 5.5709 30.0057

5 35.5322 5.5285 30.0037 10 353826 53741 30.0085

6. ASSAY: Complies Limit : 90.0% to 110.0%

Ingredients Lab. Content %

w/w contains

Actual content %

w/w contains

Percentage

Piroxicam IP 0.5 0.5049 100.97 %

OPINION : In the opinion of the undersigned, the sample referred to above is of standardquality as defined in the act and the rules thereunder with respect to the tests carried out

and mentioned above as perinhouseSpecification

Date : 27/04/99 Analyst Q.C.Incharge.

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SECTION - VII

REFERENCE SAMPLES

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REFERENCE SAMPLES

Ref. Sample : Piroxicam IP

Batch No : PX 028 / 200

Manufacturer : Ramdev Chem

Mfg. Date : Sept. 2000

Exp. Date : Aug 2005

Water : 0.098% w/w

Assay : 99.38% OAB

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SECTION IX

BIOAVAILABILITY STUDIES

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SECTION X

SAFETY AND TOLERANCE STUDIES

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BIOAVAILABILITY STUDIES

Babaretal prepared gels and ointment bases containing piroxicam 1% in order to study

the in-vitro release of the drug. The gel contained hypromellose,propylene glycol,sodium hydroxide, methyl and propyi hydroxybenzoates and purified water. The

modified hydrophilic bases contained white softparrafin,stearyl alcohol, sodium lauryl

sulphate, propylene glycol, sodium hydroxide, methyl and propyi hydroxybenzoates andpurified water. The emulsion basis contained liquid paraffin, isopropyi lanolate, stearic

acid TP,cetyl alcohol, self emulsifying glyceryl monostearate,triethanolamine,glycerol,

sodium hydroxide, methyl and propyi hydroxybenzoates and purified water. The generalrank order of in- vitro drug release through a cellulose membrane from all bases

evaluated was: gel basis>hydrophillic basis>emulsion basis. Drug release was adversely

affected by inclusion of ethanol or macrogol 400. The gel basis (containing also

dimethylsulphoxide) produced best in - vitro drug release both through me cellulose

membrane and hair less mouse skin.

Tsai et al found that the percutaneous absorbtion of piroxicam from an oil-in-water

ointment bases (university of California Hospital basis containing 12 % propylene

glycol), in rabbits was superior to that from three otherUSP ointments ( Simple ointment,macrogol ointment, and petrolatum rose water ointment). When the water(pH 7.2 ) in the

oil-in-water ointment basis was replaced by sodium bicarbonate-buffered solution (pH

9.2), percutaneous absorbtion of piroxicam was increased. The optimal effect wasattained with the addition of 5 % urea.

The relative bioavailabilities of two commercially available piroxicam 20 mgsuppositories in dogs were found to be similar and greater than the oral bioavailability of

a piroxicam capsule following administration of single doses of the preparation. Marked

inter individual and intra-individual difference in absorption were noted.

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SAFETY & TOLERANCE

SPECIAL PRECAUTIONSIt should not be applied over broken skin or wounds. Products containing salicylates

should be avoided or used with caution in patients with liver disease, pre-existinghypothrombinemia, vitamin Kdeficiency and before surgery. They are for external use

only and contact with eyes or mucous membranes should be avoided. To be used only

under close medical supervision during last three months of pregnancy and lactation.

PAEDIATRICS :

Not recommended in age below 6 years.

OVER 60:

Reduced dose necessary due to increased likelihood of adverse effects.

BREAST FEEDING:

Contraindicated as present inbreastmilk& safety not established.

PREGENANCY:

Contraindicated as it may affect the developing foetus.

ALCOHOL:

Avoid . Increase the risk of stomach irritation.

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SECTION XI

DETAILED REPORTS COVERING

PHARMACOLOGICAL ASPECTS

TOXICOLOGICAL ASPECTS

CLINICAL ASPECTS

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PHARMACOLOGICAL ASPECTS

Piroxicam is a non-steroidal anti-inflammatory agent used in musculoskeletol and joint

disorders . Piroxicam is well absorbed from the gastro-intestinal tract; peak plasmaconcentrations area reached 3 to 5 hours after oral dose. It is metabolised in the liver by

hydrosylation and conjugation with glucuronic acid and excreted predominantly in the

urine with smaller amounts in the faeces. Enterohepatic recycling occurs. Less than 5 %

of the dose is excreated unchanged. Piroxicam is extensively bound to plasma proteins(about 99%) and has a long plasma half-life of approximately 50 hours.

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TOXICOLOGICAL DATA

ADVERSE EFFECTS

The most frequent adverse effect occuring with Piroxicam are local irritation and

erythema , pruritus, dermatitis, photosensitivity. Oedema, Vomiting, Nausea, Heartburn,

Epigastric distress, tinnitus, skin rash. A report of the adverse reactions associated withpiroxicam received by the Medicines Safety Centre in South Africa including two

reactions,paraesthesia and hair loss, not previously recorded in the literature - Gerver

D. Adverse reaction of piroxicam. Drug intell din Pharm 1987 ; 21: 707-10

EFFECT ON SKIN;

As with otherNSAIDs, rash has occurred in patients taking piroxicam.

Phototoxic reactions have been described, Seroius skin reaction attributed to piroxicamtherapy include toxic epidermal necrolysis and pemphigus vulgaris.

EFFECTS ON THE BLOOD :

Decrease in haemoglobin and haematocrit not associated with obvious gastro-intestinal

bleeding, have occurred in patients taking piroxicam. Thrombocytopenia,thrombocytopenicpurpura and aplastic anaemia have been described in patients on

piroxicam.

EFFECTS ON THE ELECTROLYTES :

Reversible hyperkalaemichyperchloraemicacidosis in patients receiving piroxicam.

EFFECTS ON GASTRO-INTESTINAL TRACT ;

In the past it has been suggested that piroxicam may have a higher incidence of gastro-

intestinal adverse effects than other NSAIDs. However, while the commonest side effects

of piroxicam are indeed gastro-intestinal, it would appear from the present evidence thatthe overall incidence of such reactions is not appreciably higher with piroxicam than with

othernon-steroidal antiinflammatory agents.

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EFFECTS ON KIDNEYS ;

Acute nephropathy with characteristic features ofHenoch-Schonlein purpura, acute renal

failure, uraemia with hyperkalaemia, and acute intestinal nephritis have been associated

withpiroxicam.

EFFECTS ON LIVER:

A report of a patient who presented with features of acute hepatocellular injury aftertaking piroxicam 40 mg daily for 3 days; the liver disorder progressed to subacute hepatic

necrosis and the patient died.

DRUG INTERACTION :

Anticoagulants:Potentiation.

Diuretics : Increased risk of renal damage.

Aspirin : Reduces serum piroxicam.

Corticosteroids, oral anticoagulants andNSAIDs: Increased risk of bleeding.Lithium :Incresed serum lithium,

Antihypertensives: reduces the beneficial effectspfpiroxicam.

OVERDOSAGE mx

Emesis, Gastric lavage, Activated Charcoal. Monitor vital functions.General supportive and symptomatic treatment.

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PARTICULARS OF CLINICAL ASPECTS OF DRUGS

INDICATIONS :

i. Ankylosingspondylitis.ii. Rheumatoid arthritis-

iii. Oesteoarthritis of superficial joints.

iv. Acute musculoskeletal injuries,periathritis & tendinitis.v. Postoperative pains

vi. Acute gout.

vii. Dysmenorrhoea.

DOSAGE:

ADULTS : Rheumatoid arthritis, ankylosing spondylitis, osteoarthritis: 20 mg.OD.

Maintenance : 10-30 mg. OD

Acute musculoskeletal disorder: 40 mg OD/BD for 7-14 days.Maintenance : 40 mg OD/BD for 4-6 days.

CHILDREN : Over 6 yr

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SECTION XII

STORAGE DATA

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STORAGE DATA

Piroxicam should be preserved in tight, light-rsistant containersPiroxicam gel should be Stored below 30.

Hydroxyalkylatedcyclodextrin derivatives were found to reduce the stability

ofpiroxicam (0.5 mg inpH 7.4 that contained a 10-fold excess of the

cyclodextrin, stored at 21 to 71

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SHELF LIFE : STABILITY DATA

REFERENCE SAMPLES FOR STABILITY TESTING

The reference samples are picked from the hold store using the random

sampling technique. They are kept on clean pallets in the stability room.

Product :Roxicam Gel A.R.No. :UIFS 9/99-2000

Batch No, : 01 Mfg. Date : APR. 1999

Batch Size : 300 kgs Exp. Date :MAR.2001

Results of analysis & protocols of Test applied as perinhouse specification.

Storage Condition : Store in cool dry dark place.

Test Stability Spec /Pharmacopeial Limit Imth 12mth 24mthDescription Pale yellow coloured

homogenous gel

Ok Ok Ok

PH 7.0 to 8.0 7.47 7.35 7.20

Identification Positive Ok Ok Ok

Assay Piroxicam IP 0.5 % w/w 0.5049 g

-100.97 %

0.4839 g

=96.78 %

0.4721 g =

94.42 %

Analyst

Date 27/4/99 25/4/00 30/4/2001

The samples are observed for any changes in physical properties after every three months

and full analyticals testing is done after each year duration.

OPINION: The product is stable for 24 months.

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SHELF LIFE : STABILITY DATA

REFERENCE SAMPLES FOR STABILITY TESTING

The reference samples are picked from the hold store using the random

sampling technique. They are kept on clean pallets in the stability room.

Product :Roxicam Gel A.R.No. :UIFS 13/99-2000

Batch No. : 02 Mfg. Date : MAY. 1999

Batch Size : 300 kgs Exp. Date :APR.2001

Results of analysis & protocols of Test applied as perinhouse specification.Storage Condition : Store in cool dry dark place.

Test Stability Spec /Pharmacopeial Limit Imth 12mth 24 mm

Description Pale yellow colouredhomogenous gel

Ok Ok Ok

PH 7.0 to 8.0 7.59 7.46 7.31

Identification Positive Ok Ok Ok

Assay Piroxicam IP 0.5 % w/w 0.5003 g

=100.06 %

0.4941 g

=98.82 %

0.4784 g =

95.68 %

Analyst

Date 16/5/1999 22/5/00 27/5/2001

The samples are observed for any changes in physical properties after every three monthsand fall analyticals testing is done after each year duration.

OPNION: The product is stable for 24 months.

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SECTION XIII

AUTHENTICATED PRICE LIST

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THE FOLLOWING IS THE AUTHENTICATED PRICE LIST

SR. DESCRIPTION PRICEA Ex-Factory Price

B Price to pharmacy in the country of origin

C Public price in the country of origin

D C I F price to U.A.E. main ports

*E Export price (C I F ) to the neighbouring countries

* Photo copy of Certificate (Authenticated)

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SECTION XVI

NAME OF THE COMPETITIVE DRUG MANUFACTUREDBY OTHER FIRMS

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THE FOLLOWING ARE THE NAMES OF THE COMPETITIVE

DRUG MANUFACTURED BY OTHER FIRMS.

BRAND COMPANY PACKING PRICE

MINICAM GEL 0.5 % BLUE CROSS 30 gm gel 28.20

MOVON GEL 0.5 % IPCA 30 gm gel 26.50

DOLONEX GEL 0.5 % PFIZER 15 gmgel 26.24

PIROX GEL 0.5 % CIPLA 30 gm gel 27.00

FELCAM GEL 0.5 % SUNPHARMA 30 gm gel 30.00

PANCAMGEL 1.0% TALENT LAB 30 gm gel 1 29.00

A. .

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SECTION XV

OTHER COUNTRIES WHERE THE PRODUCT ISREGISTERED

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Photo copy of the certificate of registration of product in other country

NOT REGISTERED IN OTHER COUNTRIES

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SECTION - XVI

DATE OF INTRODUCTION OF THE PRODUCT TO THE

MARKET IN THE COUNTRY OF ORIGIN

Documents

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