1- Youcan decrease the total drug concentration in your formulation and try again.

2- You can also estimate the capacity of your lipids for any amount of drug if you have total lipiod content and drug solubility in lipids.

Good Luck

Dear Hamid

So if i decreases the drug content should i keep the drug to lipid ratio similar as before or to just lower the drug but keep the lipid content similar?

thx

manish

Hi Manish

You are worried about capacity of your lipid for solubilization of the drug. Therefore, I think you should decrease drug/lipid ratio; more lipid for less drug.

Hamid

HI Vijay

Thanks for the response.  Another question that comes to my mind is that, if the lipophilic drug is insoluble in the aqueous medium would it not stick to the surfaces of the liposomal particles? and if by centrifuging the sample would it not include the drug too?  is there another way to separate the two phases?  i would appreciate some thoughts.

thx

manish

thanks for your response. The drug is soluble in acetonitrile, methanol and ethanol. i did check by adding 200µl of the liposomal suspension to about 800µl of 20% ACN in PBS pH5.5 and i was getting a very small fraction of drug as encapsulated b/c of the poor solubility of the drug in the medium. i was hesitant to go beyond this because the drug could disoolve the DSPC lipid used and could artificially alter the drug loading.  My drug has three pka values.  pKa1, pKa2, and pKa3 value of 7.8, 8.5, and 9.0.  The drug become unstable as pH closer to neutral or even crossing pH6 hence i have kept the current formulation pH value around 5.5 as the formulation is intended for opthalmic use. The drug to the lipid ratio were 1:4, 1:7 and 1:9 and practically the drug loading did not change much which was odd. let me know ur thoughts.

thanks

manish

OMG I am facing the same problem. But as you suggest, I can do an extraction. But it happens that my analite is Vitamin D and it is REALLY not soluble in water so I think it's difficult to separate it from my phsopholipids. Do you know what more can i do in order to separate vitamin D from phospholipids and calculate EE% more efficiently? Manish finally what did you do? Thanks!