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Dear All,
Does any one can share their experience of converting poorly soluble BCS class -2 drug (base) into
salt form can reduce its positive food effect?
In other words, do the conversion of salt for BCS class-2/4 drug can result in alteration in the
food effect
If there are any example, kindly share the drug name(s) too. I appreciate your reply in this matter.
Best wishes & Regards
A.Karthik
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Dear A. Karthik
Following article may help you to predict food effect upon salt conversion.
Predicting Effect of Food on Extent of Drug Absorption Based on Physicochemical Properties
Pharmaceutical Research, Vol. 24, No.6, June 2007
Best regards,
Jignesh
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Dear Karthic
According to my experience, converting a poorly soluble drug into salt form doesn't result
systematically into reducing the food effect. It depends on the Pka value of your drug and its
solubility in different pH values found along the gastrointestinal tract.
After a high fat meal, the in situ measurement of the pH values found in the duodenum of healthy
volunteers showed that the pH was dropped from 6.2 - 6.5 to 4.5. The decrease of the pH value was
found in the three healthy volunteers in the study but not at the same time after having a meal.
After reaching the pH value of 4.5, all of the 3 subjects have showed again a slight increase in the
pH value as a function of time to reach their initial value in the range of pH 6.2 -6.5.
I hence recommend to assess the solubility in the range of 4.5 to 7.4 or to check if the ionization
state of your drug may be different in that range of pH values according to the Pka of the drug.
Also, there is another strategy to overcome food effect of poorly soluble drugs using a suitable
formulation rather than the salt form. Again, it is a case by case basis.
Warmest regards
Jean
Jean PACHOT, President & CSO
Oroxcell SAS
www.oroxcell.com
Parc technologique Biocitech
102, Avenue Gaston Roussel
F-93230, Romainville
jean.pachot.-a-.oroxcell.com
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Noelle,
Depending on how much material you have, you may want to process the whole gemisch through a small
HP-20 column. Elute with deionized water to get rid of the salts and some proteins etc. Then
increase the organic concentration (acetonitrile or methanol) to elute your compound. While you
have tried with SPE clean-up, sometimes SPE cartridges are not as effective.
Good luck,
Ving J. Lee
CEO-CSO
Adesis Inc.
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