Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Smooth muscle relaxant; antispasmodic.
DEFINITION
Mebeverine Prolonged-release Capsules contain Mebeverine Hydrochloride. They are formulated so that the Mebeverine Hydrochloride is released over a period of several hours.
The capsules comply with the requirements stated under Capsules and with the following requirements.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of Mebeverine Hydrochloride. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
Content of mebeverine hydrochloride, C25H35NO5,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of powdered capsule contents containing 0.2 g of Mebeverine Hydrochloride in 20 mL of water, add 5 mL of 5M sodium hydroxide and extract with two 25-mL quantities of dichloromethane. Dry the combined extracts over anhydrous sodium sulfate and evaporate the solvent. The infrared absorption spectrum of the oily residue, Appendix II A, is concordant with the reference spectrum of mebeverine (RS 208).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in solution A.
Solution A 3 volumes of acetonitrile and 7 volumes of mobile phase A.
(1) Shake a quantity of powdered capsule contents containing 50 mg of Mebeverine Hydrochloride with 50 mL of solution A, mix with the aid of ultrasound and shake intermittently. Dilute to 100 mL, mix and filter (a 0.45-µm nylon filter is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes. Dilute 1 volume of the resulting solution to 5 volumes.
(3) 0.05% w/v of mebeverine impurity standard BPCRS.
(4) 0.0001% w/v of mebeverine impurity C BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated end-capped octadecylsilyl silica gel for chromatography (5 µm) (Inertsil ODS-3 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 263 nm.
(f) Inject 10 µL of each solution.
MOBILE PHASE
Mobile phase A 1 volume of triethylamine and 1000 volumes of 0.38% w/v ammonium acetate, adjusted to pH 3.0 with orthophosphoric acid.
Mobile phase B Acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-5 | 70 | 30 | isocratic |
| 5-15 | 70→30 | 30→70 | linear gradient |
| 15-25 | 30 | 70 | isocratic |
| 25-27 | 30→70 | 70→30 | linear gradient |
| 27-35 | 70 | 30 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to mebeverine (retention time about 12 minutes) are: impurity C, about 0.3 and impurity D, about 0.6.
SYSTEM SUITABILITY
The test is not valid unless:
in the chromatogram obtained with solution (3), the resolution between the peaks due to impurities C and D is at least 15; in the chromatogram obtained with solution (4), the signal-to-noise ratio of the peak due to impurity C is at least 20.
LIMITS
Identify any peaks corresponding to impurities C and D in the chromatogram obtained with solution (1), using the chromatogram obtained with solution (3), and multiply the area of the peak corresponding to impurity D by a correction factor of 0.4.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (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 total impurity content is not greater than 1.0%.
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh the contents of 20 capsules. Mix, and powder if necessary. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix, with the aid of ultrasound and intermittent shaking, a quantity of powdered capsule contents containing 25 mg of Mebeverine Hydrochloride in 70 mL of methanol. Dilute to 100 mL with methanol and filter (a 0.45-µm nylon filter is suitable). Dilute 1 volume to 5 volumes with the mobile phase.
(2) 0.025% w/v of mebeverine hydrochloride BPCRS in methanol. Dilute 1 volume of the solution to 5 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base deactivated end-capped octadecylsilyl silica gel for chromatography (5 µm) (Inertsil ODS-3 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use a column temperature of 25°.
(e) Use a detection wavelength of 263 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
380 volumes of acetonitrile and 620 volumes of 0.38% w/v ammonium acetate, previously adjusted to pH 5.2 using glacial acetic acid.
When the chromatograms are recorded under the prescribed conditions, the retention time of mebeverine is about 10 minutes.
DETERMINATION OF CONTENT
Calculate the content of mebeverine hydrochloride, C25H35NO5,HCl, in the capsules from the chromatograms obtained and using the declared content of C25H35NO5,HCl in mebeverine hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities C and D listed under Mebeverine Hydrochloride.
