Which of the following chemical modifications would likely increase the water solubility of a drug?
  1. Conversion of an anhydrous form to a tri-hydrate
  2. Conversion from a crystalline to an amorphous form
  3. The addition of a lipophilic side group
  4. The removal of a hydroxyl group
Explanation
Answer - B - Amorphous forms have greater solubility than crystalline forms. Anhydrous (without water) compounds have greater solubility than when they become hydrated. Lipophilic indicates “fat-loving,” so a lipophilic side group would decrease solubility as would the removal of a hydroxyl (-OH) group.
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