Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Non-selective phosphodiesterase inhibitor (xanthine); treatment of reversible airways obstruction.
DEFINITION
Theophylline Prolonged-release Tablets contain Theophylline or Theophylline Hydrate. The are formulated so that the medicament is released over a period of several hours.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of Theophylline. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of theophylline, C7H8N4O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
B. Extract a quantity of the powdered tablets containing the equivalent of 0.2 g of theophylline with 10 mL of a mixture of 60 volumes of chloroform and 40 volumes of methanol, filter and evaporate the filtrate to dryness. The residue yields the reaction characteristic of xanthines, Appendix VI.
TESTS
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using a TLC silica gel F254 plate and a mixture of 10 volumes of concentrated ammonia, 30 volumes of acetone, 30 volumes of chloroform and 40 volumes of butan-1-ol as the mobile phase. Apply separately to the plate 10 µL of each of the following solutions. For solution (1) mix with the aid of
ultrasound a quantity of the powdered tablets containing the equivalent of 0.2 g of theophylline with 10 mL of a mixture of 60 volumes of chloroform and 40 volumes of methanol and centrifuge. For solution (2) dilute 1 volume of solution (1) to 200 volumes with a mixture of 60 volumes of chloroform and 40 volumes of methanol. After removal of the plate, allow it to dry in air and view under ultraviolet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the principal spot in the chromatogram obtained with solution (2) (0.5%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 1 mL of methanol to a quantity of the powdered tablets containing the equivalent of 0.1 g of theophylline, mix and add 50 mL of water. Dissolve with the aid of ultrasound, swirling occasionally, dilute to 100 mL with water and mix thoroughly. Dilute 5 mL to 50 mL with water. Solution (2) contains 0.01% w/v of theophylline BPCRS in water.
The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 3.9 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable), (b) as the mobile phase with a flow rate of 1.8 mL per minute a mixture of 250 volumes of methanol and 750 volumes of water and (c) a detection wavelength of 270 nm.
Calculate the content of C7H8N4O2 in the tablets using the declared content of C7H8N4O2 in theophylline BPCRS.
LABELLING
When the active ingredient is Theophylline Hydrate the quantity is stated in terms of the equivalent amount of theophylline.
