Preparation of 2% lignocaine gel (according to U.S.

P)
Formulation:
Active:
 Lignocaine/lidocaine hydrochloride

Exceipients:
 Methyl paraben base
 Propyl paraben base
 Carboxy methyl cellulose sodium
 Propylene gycol
 Sodium hydroxide
 Distilled water Q.S

Instruments required:
 Bunsen burner
 Conical flask
 Beaker
 Stirrer
 Pipette
 Wire mesh

Chemicals required:
 Lignocaine hydrochloride--- 6.6g
 Methyl paraben base-------- 0.6
 Propyl paraben base--------- 0.3g
 Propylene glycol-------------- 90g
 CMC sodium------------------- 6.7g
 Distill water Q.s--------------- 300g

Batch size:
300g

Unit packet:
15g
Standard manufacturing process:
 Before starting the manufacturing process, the equipment and instruments must be cleaned
according to SOPs.
 Take 100ml warm distill water and dissolve Methyl paraben, propyl paraben and Carboxy methyl
cellulose in it and mix them.
 Let it soak for 2 hours.
 Add lidocaine hydrochloride in propylene glycol and mix them carefully.
 Now transfer this mixture to the previous mixture and mix them until a gel like constituency is
obtained.
 Take a sample and perform identification tests on it.

Lidocaine Hydrochloride Jelly Monograph

» Lidocaine Hydrochloride Jelly is Lidocaine Hydrochloride in a suitable, water-soluble, sterile, viscous
base. It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of
lidocaine hydrochloride (C14H22N2O·HCl).

Packaging and storage— Preserve in tight containers.

USP Reference standards 11— USP Lidocaine RS.

Identification— Place in a separator containing 10 to 15 mL of water a quantity of Jelly, equivalent to

about 300 mg of lidocaine hydrochloride, mix to assure thorough dilution of the Jelly, add 4 mL of 6 N
ammonium hydroxide, and extract with four 15-mL portions of chloroform. Combine the chloroform
extracts, and evaporate with the aid of a current of warm air to dryness. Re dissolve the crystals in
solvent hexane, evaporate with the aid of warm air, and dry the residue in vacuum over silica gel for 24
hours: the lidocaine so obtained responds to Identification test A under Lidocaine.

Sterility 71: meets the requirements.

Minimum fill 755: meets the requirements.

pH 791: between 6.0 and 7.0.

Residual solvents 467: meets the requirements.

(Official January 1, 2007)

Assay— Accurately weigh into a separator containing 10 to 15 mL of water a quantity of Jelly, equivalent
to 20 to 30 mg of lidocaine hydrochloride, mix to assure thorough dilution of the Jelly, add 1 mL of 6 N
ammonium hydroxide, and extract by shaking with four 20-mL portions of chloroform. Combine the
chloroform extracts, and evaporate with the aid of a current of warm air, adding 25.0 mL of 0.01 N
sulfuric acid VS just before the last trace of chloroform is expelled. Complete the evaporation of the
chloroform, and titrate the excess acid with 0.01 N sodium hydroxide VS, determining the end point
potentiometrically (see Residual Titrations under Titrimetry 541). Each mL of 0.01 N sulfuric acid is
equivalent to 2.708mg of C14H22N2O·HCl.

Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist

Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids

USP29–NF24 Page 1253

Monographs of chemicals used are as under:

Lidocaine Hydrochloride
C14H22N2O·HCl·H2O 288.81

Acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. 2-

(Diethylamino)-2¢,6¢-acetoxylidide monohydrochloride monohydrate [6108-05-0].

Anhydrous 270.80 [73-78-9].

» Lidocaine Hydrochloride contains not less than 97.5 percent and not more than 102.5 percent
ofC14H22 N2O·HCl, calculated on the anhydrous basis.

Packaging and storage— Preserve in well-closed containers.

Labeling— Where it is intended for use in preparing injectable dosage forms, the label states that it is
sterile or must be subjected to further processing during the preparation of injectable dosage forms.

USP Reference standards 11— USP Endotoxin RS. USP Lidocaine RS.

Identification—

A: Dissolve about 300 mg in 5 to 10 mL of water in a separator, add 4 mL of 6 N ammonium hydroxide,

and extract with four15-mL portions of chloroform. Combine the chloroform extracts, evaporate with
the aid of a current of warm air, and dry the residue in vacuum over silica gel for 24 hours: the
crystalline precipitate so obtained responds to the Identification tests under Lidocaine.

B: Its solutions respond to the tests for Chloride 191.

Melting range 741: between 74 and 79, the preliminary drying treatment being omitted.

Water, Method I 921: between 5.0% and 7.0%.

Residue on ignition 281: not more than 0.1%.

Sulfate— Dissolve about 200 mg in 20 mL of water, add 2 mL of 3 N hydrochloric acid, mix, and divide
into two parts. To one part of the solution add 1 mL of barium chloride TS: no more turbidity is produced
than is present in the remaining portion of the solution to which nothing has been added.

Heavy metals, Method I 231: 0.002%.

Residual solvents 467: meets the requirements.

(Official January 1, 2007)

Other requirements— Where the label states that Lidocaine Hydrochloride is sterile, it meets the
requirements for SterilityTests 71 and for Bacterial endotoxins under Lidocaine Hydrochloride Injection.
Where the label states that LidocaineHydrochloride must be subjected to further processing during the
preparation of injectable dosage forms, it meets the requirements for Bacterial endotoxins under
Lidocaine Hydrochloride Injection.
Assay—

Mobile phase— Mix 50 mL of glacial acetic acid and 930 mL of water, and adjust with 1 N sodium
hydroxide to a pH of 3.40.Mix about 4 volumes of this solution with 1 volume of acetonitrile, so that the
retention time of lidocaine is about 4 to 6minutes. Pass through a membrane filter having a 1-μm or
finer porosity, and degas. Make adjustments if necessary (seeSystem Suitability under Chromatography
621).

Standard preparation— Dissolve about 85 mg of USP Lidocaine RS, accurately weighed, with warming if
necessary, in 0.5mL of 1 N hydrochloric acid in a 50-mL volumetric flask, dilute with Mobile phase to
volume, and mix to obtain a Standard preparation having a known concentration of about 1.7 mg of
lidocaine per mL.

Assay preparation— Transfer about 100 mg of Lidocaine Hydrochloride, accurately weighed, to a 50-mL
volumetric flask,dilute with Mobile phase to volume, and mix.

Resolution preparation— Prepare a solution of methylparaben in Mobile phase containing about 220 μg
per mL. Mix 2 mL ofthis solution and 20 mL of the Standard preparation.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a
254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. USP29 The flow rate is about
1.5 mL per minute. Chromatograph about 20 μL of the Resolution preparation, and record the peak
responses as directed for Procedure: the resolution, R ,between lidocaine and methylparaben is not less
than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation for replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 20 μL) of the Assay preparation and the Standard
preparation into the chromatograph. Record the chromatograms, and measure the responses for the
major peaks. Calculate the quantity, in mg, of C14H22N2O·HCl in the portion of Lidocaine Hydrochloride
taken by the formula:

(270.80/234.34)(50C)(rU / rS)in which 270.80 and 234.34 are the molecular weights of lidocaine
hydrochloride and lidocaine, respectively; C is the concentration, in mg per mL, of USP Lidocaine RS in
the Standard preparation; and rU and rS are the lidocaine peak responses obtained from the Assay
preparation and the Standard preparation, respectively.

Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist

Methylparaben
C8H8O3

Benzoic acid, 4-hydroxy-, methyl ester. Methyl p-hydroxybenzoate [99-76-3].

» Methylparaben contains not less than 98.0 percent and not more than 102.0 percent of C8H8O3.

Packaging and storage— Preserve in well-closed containers.

USP Reference standards 11— USP Ethylparaben RS. USP Methylparaben RS.

Identification—

A: Infrared Absorption 197M.

B: Melting range 741: between 125 and 128.

Color of solution— Dissolve 1 g in alcohol, dilute with alcohol to 10 mL, and mix (Methylparaben
solution). This solution isclear and not more intensely colored than alcohol or a solution prepared
immediately before use by mixing 2.4 mL of ferricchloride CS, 1.0 mL of cobaltous chloride CS, and 0.4
mL of cupric sulfate CS with 0.3 N hydrochloric acid to make 10 mL,and diluting 5 mL of this solution
with 0.3 N hydrochloric acid to make 100 mL. Make the comparison by viewing the solutionsdownward
in matched color-comparison tubes against a white surface (see Color and Achromicity 631).

Acidity— To 2 mL of Methylparaben solution prepared in the Color of solution test add 3 mL of alcohol, 5
mL of carbondioxide-free water, and 0.1 mL of bromocresol green TS, and titrate with 0.10 N sodium
hydroxide: not more than 0.1 mL isrequired to produce a blue color.

Residue on ignition 281: not more than 0.1%, determined on 1.0 g.

Related substances—

Test solution— Prepare a solution of Methylparaben in acetone containing 10 mg per mL.

Standard solutions— Transfer 0.5 mL of the Test solution to a 100-mL volumetric flask, dilute with
acetone to volume, andmix (Standard solution A). Dissolve 10 mg, accurately weighed, of USP
Ethylparaben RS in 1 mL of the Test solution, anddilute with acetone to 10 mL (Standard solution B).

Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids

USP29–NF24 Page 1252Pharmacopeial Forum : Volume No. 31(2) Page 415

Procedure— Separately apply 2 μL of the Test solution and 2 μL of each Standard solution to a thin-layer
chromatographicplate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic
octadecylsilanized silica gel mixture.Develop the chromatogram in a solvent system consisting of a
mixture of methanol, water, and glacial acetic acid (70:30:1)until the solvent front has moved about
three-fourths of the length of the plate. Remove the plate from the chamber, mark thesolvent front, and
allow the solvent to evaporate. Examine the plate under short-wavelength UV light, and compare
theintensities of any secondary spots observed in the chromatogram of the Test solution with that of the
principal spot in thechromatogram of Standard solution A: the intensity of any individual secondary spot
in the chromatogram of the Test solutionis not greater than that of the principal spot obtained in the
chromatogram of Standard solution A (0.5%). The test is not validunless the chromatogram obtained
with Standard solution B shows two clearly separated principal spots.

Organic volatile impurities, Method IV 467: meets the requirements.

Residual solvents 467: meets the requirements.

(Official January 1, 2007)

Assay— To about 1.000 g of Methylparaben, accurately weighed, add 20.0 mL of 1 N sodium hydroxide
VS, and heat atabout 70 for 1 hour. Cool rapidly in an ice bath. Carry out the titration on the solutions at
room temperature. Titrate theexcess sodium hydroxide with 1 N sulfuric acid VS, continuing the titration
until the second point of inflection and determiningthe endpoint potentiometrically (see Titrimetry 541).
Perform a blank determination (see Residual Titrations underTitrimetry 541. Each mL of 1 N sodium
hydroxide is equivalent to 152.1 mg of C8H8O3.

Auxiliary Information— Staff Liaison : Catherine Sheehan, B.Sc., Scientist

Expert Committee : (EM105) Excipient Monographs 1

USP29–NF24 Page 3374Pharmacopeial Forum : Volume No. 30(4) Page 1445.

Carboxymethylcellulose Sodium
» Carboxymethylcellulose Sodium is the sodium salt of a polycarboxymethyl ether of cellulose.
Itcontains not less than 6.5 percent and not more than 9.5 percent of sodium (Na), calculated on
thedried basis.

Packaging and storage— Preserve in tight containers.

Labeling— Label it to indicate the viscosity in solutions of stated concentrations.

Identification— Add about 1 g of powdered Carboxymethylcellulose Sodium to 50 mL of water, while

stirring to produce auniform dispersion. Continue the stirring until a clear solution is produced, and use
the solution for the following tests.

A: To 1 mL of the solution, diluted with an equal volume of water, in a small test tube, add 5 drops of 1-
naphthol TS. Inclinethe test tube, and carefully introduce down the side of the tube 2 mL of sulfuric acid
so that it forms a lower layer: a red-purple color develops at the interface.

B: To 5 mL of the solution add an equal volume of barium chloride TS: a fine, white precipitate is formed.

C: A portion of the solution responds to the tests for Sodium 191.

Viscosity 911— Determine the viscosity in a water solution at the concentration stated on the label.
Using undriedCarboxymethylcellulose Sodium, weigh accurately the amount that, on the dried basis, will
provide 200 g of solution of thestated concentration. Add the substance in small amounts to about 180
mL of stirred water contained in a tared, wide-mouthbottle, continue stirring rapidly until the powder is
well wetted, add sufficient water to make the mixture weigh 200 g, andallow to stand, with occasional
stirring, until solution is complete. Adjust the temperature to 25 ± 0.2, and determine theviscosity, using
a rotational type of viscosimeter, making certain that the system reaches equilibrium before taking the
finalreading. The viscosity of solutions of 2% or higher concentration is not less than 80.0% and not
more than 120.0% of thatstated on the label; the viscosity of solutions of less than 2% concentration is
not less than 75.0% and not more than 140.0%of that stated on the label.

pH 791: between 6.5 and 8.5 in a solution (1 in 100).

Loss on drying 731— Dry it at 105 for 3 hours: it loses not more than 10.0% of its weight.

Heavy metals, Method II 231— Determine as directed in the test for Heavy metals under
Methylcellulose, using a 1.0-gspecimen: the limit is 20 μg per g.

Organic volatile impurities, Method IV 467: meets the requirements.

Residual solvents 467: meets the requirements.

(Official January 1, 2007)

Assay— Transfer to a beaker about 500 mg of Carboxymethylcellulose Sodium, accurately weighed, add
80 mL of glacialacetic acid, heat the mixture on a boiling water bath for 2 hours, cool to room
temperature, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically.
Each mL of 0.1 N perchloric acid is equivalent to 2.299 mg of Na.

Auxiliary Information— Staff Liaison : Hong Wang, Ph.D. , Senior Scientific Associate

Expert Committee : (EM205) Excipient Monographs 2

USP29–NF24 Page 388Pharmacopeial Forum : Volume No. 31(5) Page 1349.

Propylene Glycol
C3H8O2 76.09

1,2-Propanediol. 1,2-Propanediol [57-55-6].

» Propylene Glycol contains not less than 99.5 percent of C3H8O2.

Packaging and storage— Preserve in tight containers.

USP Reference standards 11— USP Propylene Glycol RS.

Identification, Infrared Absorption 197F on undried specimen.

Specific gravity 841: between 1.035 and 1.037.

Acidity— Add 1 mL of phenolphthalein TS to 50 mL of water, then add 0.1 N sodium hydroxide until the
solution remainspink for 30 seconds. Then add 10 mL of Propylene Glycol, accurately measured, and
titrate with 0.10 N sodium hydroxideuntil the original pink color returns and remains for 30 seconds: not
more than 0.20 mL of 0.10 N sodium hydroxide isrequired.

Water, Method I 921: not more than 0.2%.

Residue on ignition— Heat 50 g in a tared 100-mL shallow dish until it ignites, and allow it to burn
without furtherapplication of heat in a place free from drafts. Cool, moisten the residue with 0.5 mL of
sulfuric acid, and ignite to constantweight: the weight of the residue does not exceed 3.5 mg.

Chloride 221— A 1-mL portion shows no more chloride than corresponds to 0.10 mL of 0.020 N
hydrochloric acid(0.007%).

Sulfate 221— A 5.0-mL portion shows no more sulfate than corresponds to 0.30 mL of 0.020 N sulfuric
acid (0.006%).

Heavy metals 231— Mix 4.0 mL with water to make 25 mL: the limit is 5 ppm.

Organic volatile impurities, Method IV 467: meets the requirements.

Residual solvents 467: meets the requirements.

Assay—

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a
thermal conductivitydetector, and contains a 1-m × 4-mm column packed with 5% G16 on support S5.
The injection port temperature is 240, the detector temperature is 250, and the column temperature is
programmed at a rate of 5 per minute from 120 to 200, and helium is used as the carrier gas. The
approximate retention time for propylene glycol is 5.7 minutes, and the approximate retention times for
the 3 isomers of dipropylene glycol, when present, are 8.2, 9.0, and 10.2 minutes, respectively.
Procedure— Inject a suitable volume, typically about 10 μL, of Propylene Glycol into a suitable gas
chromatograph, and record the chromatogram. Calculate the percentage of C3H8O2 in the Propylene
Glycol by dividing the area under the propylene glycol peak by the sum of the areas under all of the
peaks, excluding those due to air and water, and multiplying by 100.

Auxiliary Information— Staff Liaison : Catherine Sheehan, B.Sc., Scientist

Expert Committee : (EM105) Excipient Monographs 1

USP29–NF24 Page 1850

Sodium Hydroxide
NaOH 40.00

Sodium hydroxide. Sodium hydroxide [1310-73-2].

» Sodium Hydroxide contains not less than 95.0 percent and not more than 100.5 percent of total
alkali,calculated as NaOH, including not more than 3.0 percent of Na2CO3.

Caution—Exercise great care in handling Sodium Hydroxide, as it rapidly destroys tissues.

Packaging and storage— Preserve in tight containers.

Identification— A solution (1 in 25) responds to the tests for Sodium 191.

Insoluble substances and organic matter— A solution (1 in 20) is complete, clear, and colorless to
slightly colored.

Potassium— Acidify 5 mL of a solution (1 in 20) with 6 N acetic acid, then add 5 drops of sodium
cobaltinitrite TS: noprecipitate is formed.

Heavy metals 231— Dissolve 0.67 g in a mixture of 5 mL of water and 7 mL of 3 N hydrochloric acid.
Heat to boiling,cool, and dilute with water to 25 mL: the limit is 0.003%.

Residual solvents 467: meets the requirements.

(Official January 1, 2007)

Assay— Dissolve about 1.5 g of Sodium Hydroxide, accurately weighed, in about 40 mL of carbon
dioxide-free water. Coolthe solution to room temperature, add phenolphthalein TS, and titrate with 1 N
sulfuric acid VS. At the discharge of the pinkcolor of the indicator, record the volume of acid solution
required, add methyl orange TS, and continue the titration until apersistent pink color is produced. Each
mL of 1 N sulfuric acid is equivalent to 40.00 mg of total alkali, calculated as NaOH,and each mL of acid
consumed in the titration with methyl orange is equivalent to 106.0 mg of Na2CO3.

Auxiliary Information— Staff Liaison : Catherine Sheehan, B.Sc., Scientist

Expert Committee : (EM105) Excipient Monographs 1

USP29–NF24 Page 3424