Lidocaine and Chlorhexidine Gel

Local anaesthetic; Class I antiarrhythmic and Antiseptic.

Lidocaine and Chlorhexidine Gel is a sterile solution of Lidocaine Hydrochloride containing 0.25% v/v of Chlorhexidine Gluconate Solution in a suitable water-miscible basis.

The gel complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.

95.0 to 105.0% of the stated amount.

0.225 to 0.275% v/v.

To a quantity of the gel containing the equivalent of 80 mg of anhydrous lidocaine hydrochloride add 4 mL of hydrochloric acid and heat on a water bath for 10 minutes. Allow to cool, transfer to a separating funnel with the aid of 20 mL of water, add 5m sodium hydroxide until precipitation is complete and extract with two 20 mL quantities of chloroform. Filter the chloroform extracts through anhydrous sodium sulfate and evaporate the filtrate to dryness on a water bath using a current of nitrogen. The residue complies with tests A, B and C.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of lidocaine (RS 202).

B. Dissolve 20 mg in 1 mL of ethanol (96%), add 0.5 mL of a 10% w/v solution of cobalt(ii) chloride and 0.5 mL of 5m sodium hydroxide and shake for 2 minutes. A bluish-green precipitate is produced.

C. Dissolve 40 mg in 5 mL of a 1% w/v solution of cetrimide and add 1 mL of 5m sodium hydroxide and 1 mL of bromine water. An orange colour is produced.

D. In the Assay for chlorhexidine gluconate solution, the chromatogram obtained with solution (2) shows a peak with the same retention time as the peak due to chlorhexidine acetate in the chromatogram obtained with solution (1).

Not more than 8 ppm of 2,6-dimethyl-aniline and not more than 1.5 ppm of 4-chloro-aniline when determined in the following manner. Carry out the method for gas chromatography, Appendix III B.

(1) Shake 0.2 g of the gel with 20 mL of a mixture of 20 volumes of ether and 80 volumes of hexane and 5 mL of a buffer solution prepared by adjusting the pH of 0.1m sodium citrate to 5.0 with 0.2m sodium hydroxide, allow to separate and discard the aqueous layer. Shake the organic layer with anhydrous sodium sulfate and filter through silica-treated filter paper (Whatman 1PS is suitable), add 100 µL of heptafluorobutyric anhydride and shake for 30 seconds. Allow the solution to stand for 2 minutes, add 5 mL of 0.6m sodium hydrogen carbonate solution, shake, allow to separate and use the upper layer

(2) Dissolve 80 mg of 2,6-dimethylaniline in 1 mL of 1m hydrochloric acid with the aid of ultrasound, add sufficient water to produce 100 mL, dilute 1 volume of this solution to 50 volumes with 0.01m hydrochloric acid and further dilute 1 volume of this solution to 20 volumes with the same solvent. Shake 2 mL of this solution with 20 mL of a mixture of 20 volumes of ether and 80 volumes of hexane and 5 mL of 0.6m sodium hydrogen carbonate solution and continue in the same manner as for solution (1) beginning at the words 'allow to separate …'.

(3) Dissolve 30 mg of 4-chloroaniline in 1 mL of 1m hydrochloric acid with the aid of ultrasound, add sufficient water to produce 200 mL and dilute 1 volume to 50 volumes with the same solvent and further dilute 1 volume to 20 volumes with the same solvent. Shake 2 mL of this solution with 20 mL of a mixture of 20 volumes of ether and 80 volumes of hexane and 5 mL of 0.6m sodium hydrogen carbonate solution and continue in the same manner as for solution (1) beginning at the words 'allow to separate …'.

(a) Use a glass column (1.5 m × 4 mm) packed with acid-washed, silanised diatomaceous support (100 to 120 mesh) coated with 15% w/w of cyanopropylmethylphenyl methyl silicone fluid (OV-225 is suitable).

(b) Use nitrogen as the carrier gas at a flow rate of 50 mL per minute.

(c) Use isothermal conditions maintained at 190°.

(d) Use an inlet temperature of 200°.

(e) Use an electron capture detector at a temperature of 270°.

(f) Inject 1 µL of each solution.

In the chromatogram obtained with solution (1) the area of any peak corresponding to 2,6-dimethylaniline is not greater than the area of the principal peak in the chromatogram obtained with solution (2) and the area of any peak corresponding to 4-chloroaniline is not greater than the area of the principal peak in the chromatogram obtained with solution (3).

Complies with the test for sterility, Appendix XVI A.

Carry out the Assay described under Lidocaine Gel.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 5 mL of a 0.080% w/v solution of diphenylamine (internal standard) in the mobile phase to 5 mL of a 0.070% w/v solution of chlorhexidine acetate BPCRS in the mobile phase and dilute to 100 mL with the mobile phase

(2) Mix 10 g of the gel with sufficient of the mobile phase to produce 100 mL.

(3) Prepare solution (3) in the same manner as solution (2) but adding 5 mL of the internal standard solution before diluting to 100 mL.

(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 1.5 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 20 µL of each solution.

0.01m sodium octanesulfonate in methanol (73%) adjusted to pH 3.0 with glacial acetic acid

Calculate the content of C₂₂H₃₀Cl₂N₁₀,2C₆H₁₂O₇ from the declared content of C₂₂H₃₀Cl₂N₁₀ in chlorhexidine acetate BPCRS. Each mg of C₂₂H₃₀Cl₂N₁₀ is equivalent to 1.775 mg of C₂₂H₃₀Cl₂N₁₀,2C₆H₁₂O₇. Determine the weight per mL of the gel, Appendix V G, and express the result as the percentage volume in volume of Chlorhexidine Gluconate Solution, which contains 20% w/v of C₂₂H₃₀Cl₂N₁₀,2C₆H₁₂O₇.

Lidocaine and Chlorhexidine Gel should be stored in accordance with the manufacturer's instructions.

The label states (1) the strength with respect to Lidocaine Hydrochloride in terms of the equivalent amount of anhydrous lidocaine hydrochloride; (2) that any of the gel not used in a single application should be discarded.