title: Automatic twin vessel recrystallizer. Effective purification of acetaminophen by successive automatic recrystallization and absolute determination of purity by DSC.
abstract: I describe an interchangeable twin vessel (J, N) automatic glass recrystallizer that eliminates the time-consuming recovery and recycling of crystals for repeated recrystallization. The sample goes in the dissolution vessel J containing a magnetic stir-bar K; J is clamped to the upper joint H of recrystallizer body D. Empty crystallization vessel N is clamped to the lower joint M. Pure solvent is delivered to the dissolution vessel and the crystallization vessel via the head of the condenser A. Crystallization vessel is heated (P). The dissolution reservoir is stirred and heated by the solvent vapor (F). Continuous outflow of filtrate E out of J keeps N at a stable boiling temperature. This results in efficient dissolution, evaporation and separation of pure crystals Q. Pure solvent in the dissolution reservoir is recovered by suction. Empty dissolution and crystallization vessels are detached. Stirrer magnet is transferred to the crystallization vessel and the role of the vessels are then reversed. Evacuating mother liquor out of the upper twin vessel, the apparatus unit is ready for the next automatic recrystallization by refilling twin vessels with pure solvent. We show successive automatic recrystallization of acetaminophen from diethyl ether obtaining acetaminophen of higher melting temperatures than USP and JP reference standards by 8× automatic recrystallization, 96% yield at each stage. Also, I demonstrate a novel approach to the determination of absolute purity by combining the successive automatic recrystallization with differential scanning calorimetry (DSC) measurement requiring no reference standards. This involves the measurement of the criterial melting temperature T(0) corresponding to the 100% pure material and quantitative ΔT in DSC based on the van't Hoff law of melting point depression. The purity of six commercial acetaminophen samples and reference standards and an eight times recrystallized product evaluated were 98.8 mol%, 97.9 mol%, 99.1 mol%, 98.3 mol%, 98.4 mol%, 98.5 mol% and 99.3 mol% respectively.
authors.affiliation: Department of Molecular Structure Analysis, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aobaku, Sendai, Miyagi, 981-0905, Japan. osamnara@tohoku-pharm.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Nara
mesh_terms: D000082:Acetaminophen / Q000737:chemistry / Q000302:isolation & purification*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000302:isolation & purification*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization / Q000191:economics / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D044366:Transition Temperature
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen