Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies.
Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.
Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Ta. Petlad, Dist. Anand, Gujarat, India. vijaykparmar@gmail.com
Vijaykumar K
VK
Parmar
Shailesh A
SA
Shah
D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002627:Chemistry, Physical; D003460:Crystallization / Q000379:methods; D005473:Fluoxetine / Q000737:chemistry*; D005977:Glutarates / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008298:Maleates / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013644:Tartrates / Q000737:chemistry; D044366:Transition Temperature; D014867:Water / Q000378:metabolism; D014961:X-Ray Diffraction / Q000379:methods
D002264:Carboxylic Acids; D005977:Glutarates; D008298:Maleates; D011208:Powders; D012996:Solutions; D013644:Tartrates; D005473:Fluoxetine; D014867:Water; C030272:maleic acid; C035736:glutaric acid; C029768:tartaric acid