Aciclovir Oral Suspension

Edition: BP 2025 (Ph. Eur. 11.6 update)

General Notices

Action and use

Purine nucleoside analogue; antiviral (herpesviruses).

DEFINITION

Aciclovir Oral Suspension is a suspension of Aciclovir in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.

Content of aciclovir, C8H11N5O3

95.0 to 105.0% of the stated amount.

IDENTIFICATION

A. The light absorption, Appendix II B, in the range 230 to 250 nm of the solution prepared in the Assay before the final dilution exhibits a maximum at 255 nm and a broad shoulder at about 274 nm.

B. In the Related substances test, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak due to aciclovir in the chromatogram obtained with a solution prepared as follows.

Dissolve 25 mg of aciclovir BPCRS in 10 mL of dimethyl sulfoxide and dilute 2 volumes of the resulting solution to 5 volumes with the solvent mixture used in the Related substances test.

TESTS

Acidity

pH, 4.0 to 7.0, Appendix V L.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solution A: 1 volume of dimethyl sulfoxide and 4 volumes of water.

(1) To a quantity of the oral suspension containing 0.5 g of Aciclovir add 20 mL of dimethyl sulfoxide, shake to disperse and add sufficient solvent mixture to produce 100 mL and filter through a 0.2-μm nylon filter. Dilute 1 volume of the filtrate to 5 volumes with solution A.

(2) Dilute 1 volume of solution (1) to 100 volumes with solution A and dilute 1 volume of this solution to 5 volumes with solution A.

(3) Dissolve 5 mg of aciclovir for system suitability A EPCRS in 1 mL of dimethyl sulfoxide and dilute to 5 mL with water.

(4) Dissolve the contents of a vial of aciclovir for impurity C identification EPCRS in 200 μL of dimethyl sulfoxide and dilute to 1 mL with water. Prepare the solution immediately before use.

(5) Dissolve the contents of a vial of aciclovir for impurity G identification EPCRS in 1 mL of solution (3).

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) Supelcosil LC-18-DB is suitable).

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

(c) Use a flow rate of 1 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 10 μL of each solution.

MOBILE PHASE

Phosphate buffer solution pH 3.1 Dissolve 3.48 g of dipotassium hydrogen orthophosphate in 1000 mL of water and adjust to pH 3.1 with orthophosphoric acid.

Phosphate buffer solution pH 2.5 Dissolve 3.48 g of dipotassium hydrogen orthophosphate in 1000 mL of water and adjust to pH 2.5 with orthophosphoric acid.

Mobile phase A 1 volume of acetonitrile and 99 volumes of phosphate buffer solution pH 3.1.

Mobile phase B 50 volumes of acetonitrile and 50 volumes of phosphate buffer solution pH 2.5.

SYSTEM SUITABILITY

The test is not valid unless:

in the chromatogram obtained with solution (4), the resolution between the peaks due to impurity C and aciclovir is at least 1.5.

in the chromatogram obtained with solution (5), the resolution between the peaks due to impurity K and impurity G is at least 1.5.

LIMITS

Identify any peak in solution (1) corresponding to impurity C using the chromatogram obtained with solution (4) and multiply the area of this peak by a correction factor of 2.2.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity B is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any secondary peaks is not greater than 10 times the area of the principal peak in the chromatogram obtained with solution (2) (2.0%).

Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

ASSAY

To a weighed quantity containing 0.4 g of Aciclovir add 400 mL of water and 25 mL of 1M sulfuric acid, shake well, disperse with the aid of ultrasound for 10 minutes and add sufficient water to produce 500 mL. Filter the resulting solution, discard the first few mL of filtrate and dilute 5 mL of the filtrate to 200 mL with 0.05M sulfuric acid. Add 10 mL of the resulting solution to 5 mL of a 0.01% w/v solution of cetrimide in 0.05M sulfuric acid, add sufficient 0.05M sulfuric acid to produce 100 mL and measure the fluorescence, Appendix II E, using an excitation wavelength of 308 nm and an emission wavelength of 415 nm. Set the instrument to zero using a 0.0005% w/v solution of cetrimide in 0.05M sulfuric acid. Calculate the content of C8H11N5O3 in the oral suspension from the fluorescence obtained by carrying out the operation at the same time using a mixture prepared by adding 10 mL of a 0.002% w/v solution of aciclovir BPCRS in 0.05M sulfuric acid and beginning at the words ‘… to 5 mL of a 0.01% w/v solution of cetrimide …’. Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C8H11N5O3, weight in volume, using the declared content of C8H11N5O3 in aciclovir BPCRS.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Aciclovir.