Moxidectin Oral Gel
Action and use
Antihelminthic; ectoparasiticide
DEFINITION
Moxidectin Oromucosal Gel is a solution of Moxidectin in a suitable water-miscible basis.
The oromucosal gel complies with the requirements stated under Oromucosal Preparations and with the following requirements.
Content of moxidectin, C37H53NO8
90.0 to 110.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in methanol.
(1) Disperse a quantity of the gel containing 10 mg of Moxidectin to produce a solution containing 0.04% w/v of Moxidectin.
(2) 0.04% w/v of moxidectin BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel (Merck silica gel 60 are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, spray with anisaldehyde solution R1, heat at 105° for 5 to 10 minutes and allow to cool.
MOBILE PHASE
8 volumes of a 15% w/v solution of ammonium acetate adjusted to pH 9.6 with ammonia, 19 volumes of propan-2-ol and 43 volumes of ethyl acetate.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position, colour and size to that in the chromatogram obtained with solution (2).
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 in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of the gel in sufficient acetonitrile to produce a solution containing 1% w/v of moxidectin. Pass 6 mL of this solution with the aid of vacuum through a solid-phase extraction cartridge of 6 mL capacity containing 1g silica gel sorbent previously washed with 30 mL acetonitrile and allow to elute by gravity into a 5 mL volumetric flask. Force through any residual sample using vacuum. Add 4 mL of acetonitrile into the cartridge allowing it to elute by gravity until the 5 mL volumetric flask is filled to volume. (1.2%)
(2) Dilute 1 volume of solution (1) to 100 volumes with acetonitrile.
(3) 0.25% w/v solution of Moxidectin for System Suitability EPCRS in acetonitrile.
(4) Dilute 1 volume of solution (2) to 10 volumes with acetonitrile.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (4 μm) (Novapak C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 2.5 mL per minute.
(d) Use a column temperature of 50°.
(e) Use a detection wavelength of 242 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
Mobile phase A: 0.7% w/v solution of ammonium acetate adjusted to pH 6.0 with either glacial acetic acid or ammonium hydroxide.
Mobile phase B: acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the relative retention with reference to moxidectin (retention time about 29 minutes) of Impurity D is about 0.98.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 2.0 where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to moxidectin.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);
the sum of the areas of all the secondary peaks is not greater than 7 times the area of the principal peak in the chromatogram obtained with solution (2) (7%);
disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in acetonitrile.
(1) Disperse a quantity of the gel in sufficient acetonitrile to produce a solution containing 0.1% w/v of moxidectin and allow to settle.
(2) 0.1% w/v of moxidectin BPCRS.
(3) 0.1% w/v of moxidectin for system suitability EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (4 μm) (Novapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.5 mL per minute.
(d) Use a column temperature of 50°.
(e) Use a detection wavelength of 242 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
40 volumes of a 1.925% w/v solution of ammonium acetate in water, adjusted to pH 4.8 with glacial acetic acid, and 60 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions the relative retention with reference to moxidectin (retention time about 12 minutes) of impurity D is about 0.94.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 3.0 where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to moxidectin.
DETERMINATION OF CONTENT
Calculate the content of C37H53NO8 in the oromucosal gel using the declared content of C37H53NO8 in moxidectin BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Moxidectin
