title: Supersolubilization and amorphization of a model basic drug, haloperidol, by interaction with weak acids.
abstract: OBJECTIVE
  To present a novel approach of greatly enhancing aqueous solubility of a model weakly basic drug, haloperidol, by using weak acids that would not form salts with the drug and to attain physically stable form of amorphous drug by drying such aqueous solutions.
  
  
  METHODS
  Aqueous solubility of haloperidol in presence of increasing concentrations of four different weak organic acids (malic, tartaric, citric, fumaric) were determined. Several concentrated aqueous solutions with differing drug-to-acid molar ratios were dried in vacuum oven, and dried materials were characterized by DSC, powder XRD, dissolution testing, and stability study.
  
  
  RESULTS
  Acids were selected such that they would not form salts with haloperidol. Haloperidol solubility increased greatly with increased concentrations of malic, tartaric and citric acids, reaching >300 mg/g of solution. In contrast to the haloperidol HCl aqueous solubility of 4 mg/g, this may be called supersolubilization. Fumaric acid did not cause such solubilization as it had low water solubility. Dried solids formed dispersions of amorphous haloperidol in acids that were either amorphous or partially crystalline. Amorphous haloperidol was physically stable and had better dissolution rate than HCl salt.
  
  
  CONCLUSIONS
  A novel method of drug solubilization in aqueous media by acid-base interaction is presented. Physically stable amorphous systems of drugs may also be prepared by using this organic solvent-free approach.
authors: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York 11439, USA.
authors: Saumya
authors: S
authors: Singh
authors: Tapan
authors: T
authors: Parikh
authors: Harpreet K
authors: HK
authors: Sandhu
authors: Navnit H
authors: NH
authors: Shah
authors: A Waseem
authors: AW
authors: Malick
authors: Dharmendra
authors: D
authors: Singhal
authors: Abu T M
authors: AT
authors: Serajuddin
mesh_terms: D000143:Acids / Q000737:chemistry*; D004355:Drug Stability; D006220:Haloperidol / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012492:Salts / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000143:Acids; D012492:Salts; D012996:Solutions; D014867:Water; D006220:Haloperidol