Hello, I’m seeking your advice on the following questions:
For creams or ophthalmic solutions, how should the Maximum Daily Dose (MDD) for the active ingredient be established? Are there any guidelines or references available?
For ophthalmic solutions, I am currently considering two approaches for calculating the MDD:
1) Based on actual drop volume: (drop volume × active ingredient concentration × 2 times per day × both eyes)
Example:
0.03 mL × 20 mg/mL × 2 × 2 = 2.4 mg/day
2) Based on WHO ATC Code (assuming 0.3 mL per dose):
0.3 mL × 20 mg/mL × 2 (both eyes) = 12 mg/day
Is the first approach acceptable, or should I follow the ATC-based calculation? I am concerned that using the ATC code might lead to an excessively high assumed dose. Could you please clarify?
If anyone has a published paper or developed analytical method for N-nitroso dorzolamide, could you kindly share it?
Thank you very much for your support and expertise!
Creams is a tricky one, and will be very product specific. It will depend on what your posology is, but can vary hugely. It can be very tricky to estimate, and will depend on the surface area that it can be applied to, and how many times a day. The Scientific Committee on Consumer Safety (SCCS) has calculated the daily exposure to a leave on body lotion to be 7.8g per day (based on 2.28 applications per day), which equates to around 3.4g per application. But this is for the whole body, not just a specific area. It comes down to what you are comfortable with applying, and justifying usage wise.
For opthalmic products, personally, I would again go with the posology, based upon the dropper of your product - this should have been designed to give a specific dose, based upon concentration of active. Opthalmic drpppers look to dose 0.025 - 0.070ml typically, so your 0.03 seems to be in the right area.