title: Solid-State Characterization and Interconversion of Recrystallized Amodiaquine Dihydrochloride in Aliphatic Monohydric Alcohols.
abstract: Amodiaquine dihydrochloride monohydrate (AQ-DM) was obtained by recrystallizing amodiaquine dihydrochloride dihydrate (AQ-DD) in methanol, ethanol, and n-propanol. Solid-state characterization of AQ-DD and AQ-DM was performed using X-ray powder diffractometry, Fourier transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. All recrystallized samples were identified as AQ-DM. Crystal habits of AQ-DD and AQ-DM were shown to be needle-like and rhombohedral crystals, respectively. When AQ-DD and AQ-DM were exposed to various relative humidity in dynamic vapor sorption apparatus, no solid-state interconversion was observed. However, AQ-DM showed higher solubility than AQ-DD when exposed to bulk water during solubility study, while excess AQ-DM was directly transformed back to a more stable AQ-DD structure. Heating AQ-DM sample to temperatures ≥190°C induced initial change to metastable amorphous form (AQ-DA) which was rapidly recrystallized to AQ-DD upon ≥80%RH moisture exposure. AQ-DD was able to be recrystallized in alcohols (C1-C3) as AQ-DM solid-state structure. In summary, AQ-DM was shown to have different solubility, moisture and temperature stability, and interconversion pathways when compared to AQ-DD. Thus, when AQ-DM was selected for any pharmaceutical applications, these critical transformation and property differences should be observed and closely monitored.
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Wiriyaporn
authors.initials: W
authors.lastname: Sirikun
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.|Chulalongkorn University Drug and Health Products Innovation Promotion Center (CU.D.HIP), Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Pathumwan, Bangkok, 10330, Thailand.
authors.forename: Jittima
authors.initials: J
authors.lastname: Chatchawalsaisin
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. narueporn.s@chula.ac.th.|Chulalongkorn University Drug and Health Products Innovation Promotion Center (CU.D.HIP), Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Pathumwan, Bangkok, 10330, Thailand. narueporn.s@chula.ac.th.
authors.forename: Narueporn
authors.initials: N
authors.lastname: Sutanthavibul
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D000655:Amodiaquine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry*; D006813:Humidity; D000432:Methanol / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D014867:Water; D000655:Amodiaquine; D000431:Ethanol; D000433:1-Propanol; D000432:Methanol
keywords: amodiaquine dihydrochloride; physicochemical characterization; recrystallization; solid-state characterization; solid-state interconversion