Isotretinoin Capsules
Action and use
Vitamin A analogue (retinoid); treatment of acne.
Definition
Isotretinoin Capsules contain Isotretinoin.
Content of isotretinoin, C20H28O2
95.0 to 105.0% of the stated amount.
Identification
Tests
Dissolution
Protect the apparatus from light throughout the determination and flush the apparatus with nitrogen before use.
After 60 minutes withdraw a 20 mL sample of the medium, filter immediately through a 0.2-µm filter, discarding the first 5 mL of filtrate, and dilute the filtrate with 0.1m sodium hydroxide to give a solution expected to contain about 0.00025% w/v of Isotretinoin. Measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 343 nm, Appendix II B, using 0.1m sodium hydroxide in the reference cell.
Calculate the total content of isotretinoin, C20H28O2, in the medium taking 1490 as the value of A(1%, 1 cm) at 343 nm and divide the result by 6 to obtain the amount per capsule.
Not less than 85% of the stated amount per capsule is released after 60 minutes.
Related substances
Protect the solutions from light throughout the procedure. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
A 0.5% w/v solution of glacial acetic acid in a mixture of methanol and water, the proportions adjusted to give a retention time for tretinoin of about 15 minutes (a mixture of 23 volumes of water and 77 volumes of methanol is usually suitable).
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the peaks due to tretinoin and isotretinoin is at least 2.0.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to tretinoin is not greater than twice the area of the peak in the chromatogram obtained with solution (3) (4%);
the area of any other secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%);
the sum of the areas of any such peaks is not greater than 1.5 times the area of the peak in the chromatogram obtained with solution (2) (1.5%).
Assay
Carry out the following procedure in subdued light. Slit 10 capsules with a scalpel avoiding loss of the capsule contents, place the capsules in a 500-mL graduated flask washing any material adhering to the scalpel into the flask with 25 mL of dichloromethane per capsule and mix with the aid of ultrasound for 15 minutes. Add sufficient dichloromethane to produce 500 mL, shake for 2 minutes and dilute with a solution prepared by diluting 5 mL of 0.1m hydrochloric acid to 250 mL with ethanol (96%) to produce a solution containing 0.0008% w/v of Isotretinoin. Measure the absorbance of this solution at the maximum at 356 nm, Appendix II B, using the ethanolic hydrochloric acid solution in the reference cell. Calculate the content of C20H28O2 in the capsules taking 1350 as the value of A(1%, 1 cm) at the maximum at 356 nm.
Storage
Isotretinoin Capsules should be protected from light.