สำนักยาและวัตถุเสพติด กรมวิทยาศาสตร์การแพทย์ กระทรวงสาธารณสุขBureau of Drug and Narcotic, Department of Medical Sciences, Ministry of Public Health
Acyclovir Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the labelled amount of C8H11N5O3.
Strengths available 200, 400 and 800 mg.
Herpes simplex, treatment: 200 mg (400 mg in the immunocompromised or if absorption impaired) five times daily, usually for 5 days.
Genital herpes infection, initial episode: 200 mg every 4 hours while awake, five times a day, for 10 days.
Recurrent infections, intermittent therapy (<6 episodes per year): 200 mg every 4 hours while awake, five times a day, for 5 days.
Recurrent infections, chronic suppressive therapy (≥6 episodes per year): 400 mg twice a day, or 200 mg three to five times a day, for up to 12 months.
Herpes zoster (shingles): 800 mg every 4 hours while awake, five times a day, for 7 to 10 days.
Varicella (chickenpox): 800 mg four times a day for 5 days. Treatment should be initiated at the earliest sign or symptom of chickenpox. (Note Adults with acute or chronic renal impairment may require a reduction in dose as indicated in the table.) Children 2 years of age and over----Varicella (chickenpox): 20 mg per kg of body weight, up to 800 mg per dose, four times a day for 5 days. Treatment should be initiated at the earliest sign or symptom of chickenpox.
Warning; Precaution; Additional information See under Acyclovir, p. 21.
Packaging and storage Acyclovir Tablets shall be kept in tightly closed containers, protected from light, and stored at a temperature not exceeding 25º.
Identification The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Related substances Not more than 2.0 per cent w/w of guanine and not more than 0.5 per cent w/w of any other impurities, using the chromatograms from the Assay. Calculate the quantity, in μg, of guanine in the portion of Acyclovir Tablets taken from the peak corresponding to the peak of Guanine standard preparation and calculate the percentage of other impurities by the normalization procedure.
Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).
Dissolution medium: 0.1 M hydrochloric acid; 900 ml.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure Determine the amount of C8H11N5O3 dissolved from absorbances at the maximum at about 254 nm of filtered portions of the test solution, suitably diluted with Dissolution medium, if necessary, in comparison with a standard solution having a known concentration of Acyclovir RS in the same medium (Appendix 2.2).
Tolerances Not less than 80 per cent (Q) of the labelled amount of C8H11N5O3 is dissolved in 45 minutes.
Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
Mobile phase, System suitability solution 1 and Standard preparation Prepare as directed in the Assay under Acyclovir, p. 21.
Guanine standard preparation Dissolve an accurately weighed quantity of guanine in 0.1 M sodium hydroxide, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 2.0 μg per ml.
System suitability solution 2 Use Guanine standard preparation.
Assay preparation Weigh and finely powder not less than 10 Acyclovir Tablets. Transfer an accurately weighed quantity of the powder, containing about 10 mg of acyclovir, to a 100-ml volumetric flask, dissolve in 10 ml of 0.1 M sodium hydroxide, dilute with water to volume, mix, and filter.
Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles maintained at a temperature of 40º, (b) Mobile phase at a flow rate of about 1.5 ml per minute, and (c) an ultraviolet photometer set at 254 nm.
To determine the suitability of the chromatographic system, chromatograph System suitability solution 1, System suitability solution 2, and record the peak responses as directed under Procedure: the relative retention times are about 1.0 for guanine and 1.6 for acyclovir, the resolution factor between acyclovir and guanine is not less than 2.0, and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Procedure Separately inject equal volumes (about 20 μl) of Standard preparation, Guanine standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for all the peaks.
Calculation Calculate the content of C8H11N5O3 in the portion of the Tablets taken, using the declared content of C8H11N5O3 in Acyclovir RS.
Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).