Amphotericin Lozenges

Definition

 

Amphotericin Lozenges are compressed lozenges containing Amphotericin

 

The lozenges comply with the requirements stated under Oromucosal Preparations and with the following requirements.

 

Identification

 

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) / (N2B1-N1B2)

 

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.

 

Dissolution

 

The requirement for dissolution does not apply to Amphotericin Lozenges.

 

Assay

 

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.

 

Storage

 

Amphotericin Lozenges should be protected from light.

 

Labelling

 

The quantity of active ingredient is stated in terms of the equivalent amount of amphotericin B.