which method is best to increasing the of solubility for poorly soluble drug (diaryl compounds) in water
Drug solubility sometimes depends on pH. try to change pH it may affect solubility. you can use Chemicalize site ( chemicalize .com) to know what happens to drug solubility with different pH. Also, you can use hot water instead of cold water.
Depends upon the nature of the drugs, some sort soluble in organic solvent some soluble in aqueous, acidic and basic media. For increasing in solubility organic solvent choice of polar non- polar solvents. for aqueous addition of strong acids or strong basic media. heating is also increase solubility.
Yes thank you dear researchers for your kind reply my doubts
I am already working on it to ph. optimization but some i have to face some lacking for preclinical formulation of my lead compound
I need clear protocol of my lead compound to increasing solubility
some peoples are already done for this (Article Release Kinetics Study of Poorly Water-Soluble Drugs from Na...
)kind for work but i had some confusion for this protocol any one can you please help to write the specific protocol my lead compound
Dear Manikandan,
when a drug is poorly soluble in water you cannot change the solubility of the drug alone at a given temperature. Heating can increase the solubility, but upon colling the drug will precipitate again. However, you can change / improve the solubility e.g. by adding other solvents like DMSO, by playing with the pH value, or by addition of additives (prodrugs) which will alter the solubility. For an interesting literature reference about that last aspect please have a look at the following article:
The Prodrug Approach: A Successful Tool for Improving Drug Solubility
The paper has been published Open Access, which means that it is freely available from the internet (please see attached pdf file).
Good luck with your research!
First, I do not think that any drug consists of just two aryl groups. What other functional groups are present? Based on those "other" functional you can decide on an approach. Second, the water solubility that is important is the solubility of the drug in pH 7.4 water which is what the pH will be in vivo unless it binds to various protein that increase the apparent solubility. You can change the pH of the water by making it acidic or basic but that does not change the solubility in pH 7.4 water. Third, you can make a prodrug. Use one of those "other" functional groups in the drug to transiently attach a promoiety containing a water solubilzing functional group to one of them. A phosphonooxymethyl promoiety can be attached to a wide variety of functional groups in the drug where the terminal phosphate group is highly ionized at pH 7.4 and will transiently increase the water solubility, but there are text book written about other possibilities.
Thank you so much for prompt response my doubt. and my lead compound is hydrophobic nature finally i need without functional group modification and structural changes i need to increasing the solubility of lead compound
i need clear protocol for preclinical formulation of my compound like ph. optimization or inclusion complex or else
Dear Manikandan,
thanks for your kind response. For a good overview on various ways of how to overcome this solubility problem please also have a look at the following potentially useful article:
Improvement in solubility of poor water-soluble drugs by solid dispersion
Article Improvement in solubility of poor water-soluble drugs by sol...
Fortunately this helpful paper has been posted by the authors as public full text. Thus you can freely download it as pdf file.
Good luck with your work!
Dear all, there different way in doing solubilization of poorly soluble drugs. Micellization by surfactants and polymers, co-solvation by special additives, and others. Please have a look at the following documents, where the 2nd reference may be close to your case. My Regards
https://doi.org/10.1002/9781118573983.ch3
https://doi.org/10.1002/jps.22241
https://doi.org/10.1016/j.ejpb.2006.06.003
https://doi.org/10.1016/j.ijpharm.2006.03.042
10.1100/2012/718791
10.2174/1872211311307020004
https://doi.org/10.1100/2012/718791
Dear all Thank you for your valuable inputs and sharing your thoughts and experiences with me,
And I am already work with procedure
Like PEGlyated based one, inclusion complex. In pH (2
4) using HPMC, and DMA
It's not good result in oral mice
Hi Manikandan,
You may try the following:
1.SLS in formulation at 3-5%w/w: This will help in wetting and also increase the rate of solubilization of your DS
2. If you are using crystalline form of the DS, convert it to amorphous form by spray drying and check the change in solubility with the amorphous form as well. If the amorphous form is poorly soluble too, then you can use HME with a hydrophilic excipient for molecular dispersion of your drug with the excipient.
3. Also you may use bile salts -Potassium and Sodium Taurocholates in your solubilizing vehicle
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs