Suppose poorly soluble drug having 600mg dose. After 50 times increase in solubility of that drug what can be the dose of that poorly soluble drug?
dose determination can not be determined unless the new drug passes the preclinical studies(chemistry, physical properties, pharmacology, toxicology and preformulation study & others), then clinical trials (phases I, II, and III). after that the bioavailability of the specified dose becomes well known, and therefore any increase in the solubility that may increase the dissolution rate and increase the bioavailability can be determined and therefore the dose can be reduced to achieve the same drug blood level that is effective but still below the toxic level
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you r right but my question is that i hv choosen drug having dose 6oomg . i hv incresed its solubility(dissolution) by Complexation by 50 times. then what dose should be taken for making formulation after solubiity enhancement......as my view is 12 mg dose should be considered after complexation.....Is tht right?????
Dear Mayur, how did you enhanced the solubility of your drug. I have an assignment as well for the solubility enhancement of Clofamizine, a lipid soluble drug.
You cannot make the assumption that increasing the solubility 50 fold would result in 50 fold increase in bioavailability. For example if you increased the "apparent solubility", e.g., cyclodextrins and thus increased surface area or used a co-solvent (new solubility) they can alter rate of absorption. Depending on the physicochemical properties of the drug and its mechanism of absorption (passive, facilitated or active transporter) - likely passive if very lipophilic, you may alter the rate of absorption but not overall bioavailability. If it is a controlled release approach you may "miss" the "window" of absorption and this could also lead to alteration in absorption. You can determine this by doing a simple oral bioavailability study in species of interest (rat, dog, etc.,). Good luck
Dear Syed sir , i have increased solubility by Cyclodextrin complexation Solid dispersion method..........You can also try for clofamizine by using Cyclodextrin , PEG solid dispersion method(Kneading Method).....
Regards
Thank you so much Mayur, I have added this method in my methods after your suggestion. Regards
Mayur,
if you are doing a project -- i.e formultion with solubility enhnced rug-- then use the solid dispersion having equivalent amount of coventionl dose i.e 600mg.
then carry out comprative dissolution plin drug and solubility enhanced drug.
see the difference in drug release -- and ascertain whether there is significant advantage in terms of drug release. but bioavailbility is different issue. it cannot done so esily as pointed out Robert arnold and N yousof.
congratulations for increasing solubility by 50 times. i agree with Robert arnold and bijay ghosh. keep the same dose. carry out the dissolution study for both (marketed formulation and your formulation) after selection of descriminative dissolution media.
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