Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drug.
The effect of chloride ion (Cl-) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01 M HCl from rotating disks followed the order of mesylate>>phosphate>hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form.
Li
Shoufeng
S
Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey 07936, USA.
Doyle
Pamela
P
Metz
Stephanie
S
Royce
Alan E
AE
Serajuddin
Abu T M
AT
D002626:Chemistry, Pharmaceutical; D002712:Chlorides / Q000737:chemistry* / Q000494:pharmacology; D006220:Haloperidol / Q000737:chemistry*; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008698:Mesylates / Q000737:chemistry; D009994:Osmolar Concentration; D010316:Particle Size; D010756:Phosphoric Acids / Q000737:chemistry; D011208:Powders; D012492:Salts / Q000737:chemistry; D012995:Solubility / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
D002712:Chlorides; D008698:Mesylates; D010756:Phosphoric Acids; D011208:Powders; D012492:Salts; C045880:methanesulfonic acid; C030242:phosphoric acid; D006220:Haloperidol; D006851:Hydrochloric Acid