Conversion of solid dispersion prepared by acid-base interaction into free-flowing and tabletable powder by using Neusilin® US2.
A novel method of greatly increasing solubility and dissolution rate of a model basic drug, haloperidol, by interacting it with water-soluble weak organic acids in aqueous media was previously reported in the literature. Amorphous solid dispersion (SD) was formed when solutions containing haloperidol and various acids were dried. However, the SDs were semisolid, viscous and sticky, especially when the drug load was high, and could not be processed into tablets. The drug release from SD was also incomplete since the viscous material did not readily mix with aqueous media. In the present study, a mesoporous metalosilicate, Neusilin(®) US2, was incorporated in SDs prepared by using malic, tartaric and citric acids. The silicate constituted 40% w/w of the total solid mass. The addition of silicate converted SDs into powders, which were then characterized for flow properties, bulk and tap density, and tabletability. Their physical properties were found to be acceptable for the development of tablets. DSC and powder XRD showed that haloperidol and acids converted completely to amorphous forms, and they did not show any sign of crystallization during accelerated stability study at 40°C/75% RH and 25°C/60% RH for 9 months. Complete drug release under gastrointestinal pH conditions could be obtained from tablets prepared.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Ankita
A
Shah
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA. Electronic address: serajuda@stjohns.edu.
Abu T M
AT
Serajuddin
D017607:Aluminum Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006220:Haloperidol / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D017616:Magnesium Compounds / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011208:Powders; D017640:Silicates / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D014961:X-Ray Diffraction
D017607:Aluminum Compounds; D017616:Magnesium Compounds; D010592:Pharmaceutic Aids; D011208:Powders; D017640:Silicates; D013607:Tablets; C033065:aluminum magnesium silicate; D006220:Haloperidol
Amorphous solid dispersion; Haloperidol; Neusilin(®) US2; Poorly water-soluble drug; Supersolubilization; Weak organic acid