Aciclovir Tablets

General Notices

Action and use

Purine nucleoside analogue; antiviral (herpesviruses).

Definition

Aciclovir Tablets contain Aciclovir.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of aciclovir, C₈H₁₁N₅O₃

95.0 to 105.0% of the stated amount.

Identification

A. To a quantity of the powdered tablets containing 0.1 g of Aciclovir add 60 mL of 0.1m sodium hydroxide and disperse with the aid of ultrasound for 15 minutes. Add a sufficient quantity of 0.1m sodium hydroxide to produce 100 mL, mix well and filter. To 15 mL of the filtrate add 50 mL of water and 5.8 mL of 2m hydrochloric acid and sufficient water to produce 100 mL. To 5 mL of the solution add sufficient 0.1m hydrochloric acid to produce 50 mL and mix well. The light absorption, Appendix II B, in the range 230 to 350 nm of the solution exhibits a maximum at 255 nm and a broad shoulder at about 274 nm.

B. In the Assay, 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 solution (2).

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions

(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.

(b) Use 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.

procedure

After 45 minutes, withdraw a 25 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 255 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell.

determination of content

Calculate the total content of aciclovir, C₈H₁₁N₅O₃, in the medium from the absorbance obtained and taking 560 as the value of A(1%, 1 cm) at the maximum at 255 nm.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a solvent mixture of 1 volume of dimethyl sulfoxide and 4 volumes of water unless otherwise indicated.

(1) Shake a quantity of the powdered tablets containing 25 mg of Aciclovir with 10 mL of dimethyl sulfoxide for 15 minutes and filter.Dilute 2 volumes of the filtrate to 5 volumes with the solvent mixture.

(2) Dilute 1 volume of solution (1) to 100 volumes with the solvent mixture and further dilute 1 volume to 5 volumes with the solvent mixture.

(3) Dissolve 5 mg of aciclovir for system suitability EPCRS (containing impurities A, B, J, K, N, O and P) in 1 mL of dimethyl sulfoxide and dilute to 5.0 mL with water.

(4) Dissolve the contents of a vial of aciclovir for peak identification 1 EPCRS (containing impurities C and I) in 200 µL of dimethyl sulfoxide and dilute to 1.0 mL with water. Prepare the solution immediately before use.

(5) Dissolve the contents of a vial of aciclovir for peak identification 2 EPCRS (containing impurities F and G) in 1.0 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.

(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 3.1Dissolve 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 2.5Dissolve 3.48 g of dipotassium hydrogen orthophosphate in 1000 mL of water and adjust to pH 2.5 with orthophosphoric acid.

Mobile phase A1 volume of acetonitrile and 99 volumes of phosphate buffer solution pH 3.1.

Mobile phase B50 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 F and impurity A is at least 1.5 and the resolution between the peaks due to impurity K and G is at least 1.5.

limits

In the chromatogram obtained with solution (1):

identify any peak corresponding to impurity I using the chromatogram obtained with solution (4) and the chromatogram supplied with aciclovir for peak identification 1 EPCRS and multiply the area of this peak by a correction factor of 1.5;

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 peak corresponding to impurity O is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);

the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

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 all 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

Weigh and finely powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a solvent mixture of 1 volume of dimethyl sulfoxide and 4 volumes of water unless otherwise indicated.

(1) Shake a quantity of the powdered tablets containing the equivalent of 25 mg of Aciclovir in 10 mL of dimethyl sulfoxide and filter. Dilute 2 volumes of the filtrate to 5 volumes with the solvent mixture and further dilute 1 volume to 10 volumes with the solvent mixture.

(2) Dissolve 25 mg of aciclovir BPCRS in 10 mL of dimethyl sulfoxide. Dilute 2 volumes to 5 volumes with the solvent mixture and further dilute 1 volume to 10 volumes with the solvent mixture.

(3) Dissolve the contents of a vial of aciclovir for peak identification 1 EPCRS (aciclovir with impurities C and I) in 200 µL of dimethyl sulfoxide and dilute to 1.0 mL with water. Prepare the solution immediately before use.

chromatographic conditions

The chromatographic conditions described under Related substances may be used.