What dissolution medium can be used with poorly water-soluble drugs (BCS Class 2)? If the drug substance is not soluble in that medium, how should the standard solutions for the calibration curve be prepared?
According to USP, For oral formulations dissolution should be performed in a medium having pH range 1.2 - 6.5 and to 7.5 only for modified release substance. For poorly soluble drug, medium may contain a percentage of a surfactant (1% w/v) (polysorbate 80, SLS or lauryl dimethyl amine oxide). The medium should be deaerated by heating, filtration or by applying vacuum. The sink condition must be maintained for which the quantity of dissolution should not be less than 3 times that required to form a saturated solution of the drug substance and if required volume of the medium can be raised to 2L or 4L using large vessels. For Reference
For Reference Please refer USP
as per my knowledge the standard solution of calibration curve will be made by the completed soluble solvent not with partially soluble,if exact solubility identified only we can come to know how much drug dissolved in that medium
You can also try using biorelevant media. These media mimic the conditions in stomach and intestine much better than simply adding a surfactant to a buffer. You can either buy these media ready made from https://biorelevant.com/ or just find publications from Jennifer Dressman she has published all the compositions.
Good luck!
you may use mixture of solvent :medium , 1:1 to prepared a stock solution and get a calibration curve out of it. Then, determine the solubility of that API in the medium by dissolving\ excess API in that medium. The filtrate of the excess API solution will be saturated with API. Upon UV measurement, add in solvent to make up 1:1 base mixture. The reading will then be used to determined the solubility of your API in that poorly soluble medium. From there, you know the concentration of the API in the poorly soluble medium....utilizing the saturated solution (in poorly soluble medium), you may further prepare the calibration with 5 different dilutions.
Dear Vipul,
What's the purpose of the drug product dissolution assessment?
Is it to perform dissolution profile comparison (as when trying to conclude about the release similarity of two different products or before/after modifying the manufacturing process or formula)?
Or is to be included as a batch release and/or stability test?
Some of the above aspects have been addressed in previous comments by including references to the use of surfactants and/or a range of pH (that need to cover the physiological oral route values if intended to support a biowaiver). One should take into account that the dissolution method (which includes the medium used) must demonstrate a discriminating ability to changes between batches and/or products.
Depending on the purpose, different media may be required.
In addition, analytical standard solutions preparation (for the calibration curve) depend on the analytical method (direct UV-vis or HPLC, for instance) you are planing to use.
Regards, Luis
I think drugs belonging to BCS class 2 are soluble in propylene Glycol, N methyl pyrrolidone and DMSO.
Any budy know Diacerine Tablets Dissolution media bcuz this is class 4 and not soluble in any media + surfactant.
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