In situ salt screening--a useful technique for discovery support and preformulation studies

Pharmaceutical Development and Technology
W Q Tong, G Whitesell

Abstract

The purpose of this paper was to present an in situ salt screening technique which is applicable to most basic compounds. The theoretical aspects, experimental details, applications, and significance of this technique are illustrated through in situ salt screening studies performed on GW1818, an alpha 1A andrenergic receptor antagonist intended for treatment of benign prostatic hyperplasia (BPH). Generally, the in situ salt screening technique includes (i) acid selection, (ii) a solubility study, (iii) characterization of residual solids, and (iv) calculation of the Ksp and solubility of the salts. Six acids were screened for salt formation with GW1818. Excellent agreement was found between the solubility results determined using the authentic salts and solubility results obtained through in situ screening. Additional evidence of salt formation and some solid state properties of the salts formed in situ were obtained through microscopic examinations, differential scanning calorimetry (DSC), and x-ray powder diffraction studies. Four salts of GW1818, the phosphate, succinate, mesylate, and hydrochloride, were crystalline and demonstrated adequate solubility. These were selected for further evaluation. Adequate solubility was als...Continue Reading

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