Salt formation to DECREASE the solubility of a drug – A case study on a commercially available formulation

1. Salt formation to DECREASE the
solubility of a drug – A case study
on a commercially available
formulation
Presented by: Debanjan Das
NOTE: Typically, salt formation is carried out
to enhance solubility. Here, the reverse
process was required to adjust required
bioavailability

2. Reasons to decrease solubility
Controlled release and/or BA
Depot formulations
Ease of processing
 Ca, Mg salts of organic acids form soaps which
can tolerate the rigors of manufacturing
operations
Easier to control polymorphism with a salt of less
solubility

3. Model drug studied
Hydroxyzine
Hydroxyzine HCl
Hydroxyzine Pamoate
Ref: Hydroxyzine - A Medical Dictionary, Bibliography, and Annotated Research Guide, Icon
Health Publications; Icon Health Publications, ISBN: 0597844569, March 2004

4.  Hydroxizine
Dihydrochloride
 Hydroxizine Pamoate

5. Comparison
Hydroxizine Dihydrochloride Hydroxizine Pamoate
Solubility Very soluble in water. Very slightly soluble in
cold water.
Molecular Weight Weight: 447.83 g/mole 763.29 g/mole
Toxicity LD50 Oral Rat 950 mg/kg
LD50 IP Mouse 122 mg/kg
LD50 IP Rat 126 mg/kg
LD50 IV Mouse 48.9 mg/kg
LD50 IV Rat 45 mg/kg
ORAL (LD50): Acute:
1740 mg/kg [Rat].
1840 mg/kg [Mouse].

6. Comparison
Hydroxizine Dihydrochloride Hydroxizine Pamoate
Solubility Very soluble in water. Very slightly soluble in
cold water.
Molecular Weight Weight: 447.83 g/mole 763.29 g/mole
Toxicity LD50 Oral Rat 950 mg/kg
LD50 IP Mouse 122 mg/kg
LD50 IP Rat 126 mg/kg
LD50 IV Mouse 48.9 mg/kg
LD50 IV Rat 45 mg/kg
ORAL (LD50): Acute:
1740 mg/kg [Rat].
1840 mg/kg [Mouse].