Amphotericin Lozenges are compressed lozenges
The lozenges comply with the requirements stated
under Oromucosal Preparations and with the following requirements.
To a quantity of the powdered lozenges containing the
equivalent of 12.5 mg of amphotericin B add 2.5 ml of dimethyl sulphoxide and shake
for 5 minutes. Add 15 ml of methanol , shake for a further 10 minutes, add
sufficient methanol to produce 25 ml
and filter. Dilute 1 ml of the filtrate to 100 ml with methanol . The light
absorption of the resulting solution, Appendix II B, in the range 300 to 450 nm
exhibits three maxima, at 362, 381 and 405 nm. The ratio of the absorbance at the
maximum at 362 nm to that at the maximum at 381 nm is 0.5 to 0.6. The ratio of the absorbance
at 381 nm to that at the maximum at 405 nm is about 0.9.
Content of tetraenes
Not more than 13.3% w/w of the stated amount of amphotericin B
when determined by the following method. For solution (1) add to a quantity of the
powdered lozenges containing the equivalent of 37.5 mg of amphotericin B 5 ml of dimethyl
sulphoxide and 25 ml of methanol and
shake for 10 minutes, add sufficient methanol to
produce 50 ml, mix thoroughly and filter. Dilute 4 ml of the filtrate to 50 ml with methanol
. Prepare solution (2) by dissolving 50 mg of amphotericin B EPCRS in 5 ml of dimethyl
sulphoxide, adding sufficient methanol to
produce 50 ml and diluting 4 ml to 50 ml with methanol . For solution (3) dissolve
25 mg of nystatin EPCRS in 25 ml of dimethyl sulphoxide, dilute to 250 ml
with methanol and dilute 4 ml of the
resulting solution to 50 ml with methanol . Measure the absorbance's of
solutions (1) and (2) at the maximum at 282 nm and that of solution (3) at the same
wavelength, Appendix II B, using a 0.8% v/v solution of dimethyl sulphoxide in methanol
in the reference cell. Then measure the absorbance
of solution (3) at the maximum at 304 nm and those of solutions (1) and (2) at the same
wavelength. Calculate the A(1%, 1 cm) of the preparation being examined, at both
wavelengths, each with reference to the content obtained in the assay. Calculate the A(1%,
1 cm) of nystatin EPCRS and of amphotericin B EPCRS, at both wavelengths,
each with reference to the dried substance. Calculate the percentage content of tetraenes
(x) from the expression:
x = F + 100 (B1S2-B2S1)
where S1 and S2 are the
specific absorbance's of the preparation being examined at 282 nm and 304 nm respectively,
N1 and N2 are the specific absorbance's of nystatin
EPCRS at 282 nm and 304 nm respectively, B1 and B2
are the specific absorbance's of amphotericin B EPCRS at 282 nm and 304 nm
respectively and F is the declared content of tetraenes in amphotericin B EPCRS.
The requirement for dissolution does not apply to Amphotericin
Weigh and powder 20 lozenges. Triturate a quantity of the
powder containing the equivalent of 10 mg of amphotericin B with 10 ml of water ,
add sufficient dimethyl sulphoxide to produce 100 ml, shake for 20 minutes and
filter. Carry out the biological assay of antibiotics, Appendix XIV A. The
precision of the assay is such that the fiducial limits of error are not less than 95% and
not more than 105% of the estimated potency.
Calculate the content of amphotericin B in the lozenges taking
each 1000 IU found to be equivalent to 1 mg of amphotericin B. The upper fiducial limit of
error is not less than 90.0% and the lower fiducial limit of error is not more than 120.0%
of the stated content.
Amphotericin Lozenges should be protected from light.
The quantity of active ingredient is stated in terms of the
equivalent amount of amphotericin B.