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. 2021 May 6;25(5):1123–1142. doi: 10.1021/acs.oprd.0c00516

Table 2. Results of the Optimization of Lovastatin Crystal Yield, YAPI, for Five Crystallization Methods—Cooling Crystallization with: Only Pure Solvent Allowed in the Initial State (CP), Mixtures Allowed Throughout (CM); Antisolvent Crystallization with: Only Pure Solvent Allowed in the Initial State (ASP), Mixtures Allowed Throughout (ASM); and Hybrid Cooling and Antisolvent Crystallization (H)a.

              solvents
method rank YAPI/% χs/(g/g) T0/K
graphic file with name op0c00516_m044.jpg
graphic file with name op0c00516_m045.jpg
 s1 s2
cooling (CP) 1 97.47 73.02 361.15 1.000 1.000 n-heptane  
  2 96.33 3.50 368.75 1.000 1.000 isobutyl acetate  
  3 94.89 3.50 363.35 1.000 1.000 1-pentanol  
  4 93.46 4.11 356.35 1.000 1.000 isopropyl acetate  
  5 92.75 3.50 357.05 1.000 1.000 butyl acetate  
                 
cooling (CM) 1 97.47 73.02 361.15 1.000 1.000 n-heptane  
  2 96.45 3.50 369.15 0.962 0.962 isobutyl acetate n-pentane
  3 94.89 3.50 363.35 1.000 1.000 1-pentanol  
  4 93.46 4.11 356.35 1.000 1.000 isopropyl acetate  
  5 93.36 3.50 358.25 0.915 0.915 butyl acetate n-pentane
                 
anti-solvent (ASP) 1 92.16 85.84 293.15 1.000 0.158 methyl acetate n-heptane
  2 90.24 109.56 293.15 1.000 0.165 ethyl acetate n-heptane
  3 89.85 78.01 293.15 1.000 0.134 methyl acetate n-pentane
  4 87.22 101.97 293.15 1.000 0.139 ethyl acetate n-pentane
  5 85.62 170.49 293.15 1.000 0.174 propyl acetate n-heptane
                 
anti-solvent (ASM) 1 93.04 75.80 293.15 0.928 0.157 methyl acetate n-heptane
  2 91.67 63.10 293.15 0.882 0.133 methyl acetate n-pentane
  3 90.24 109.56 293.15 1.000 0.165 ethyl acetate n-heptane
  4 87.40 100.40 293.15 0.955 0.139 ethyl acetate n-pentane
  5 85.62 170.49 293.15 1.000 0.174 propyl acetate n-heptane
                 
hybrid (H) 1 99.23 7.93 370.35 1.000 0.174 propyl acetate n-heptane
  2 99.16 8.59 373.15 1.000 0.184 butyl acetate n-heptane
  3 98.97 7.25 370.35 1.000 0.145 propyl acetate n-pentane
  4 98.93 10.88 373.15 1.000 0.228 isobutyl acetate n-heptane
  5 98.90 7.77 373.15 0.954 0.154 butyl acetate n-pentane
a

For each method, the top five solvent mixtures are ranked with respect to the crystal yield of lovastatin achieved. The solvent consumption, χs, initial temperature, T0, and binary solvent compositions in terms of initial and final mole fractions of solvent s1, Inline graphic and Inline graphic, are also given. In all cases, the maximum allowable temperature is 373.15 K, the minimum solvent mass is 3.5 g solvent/(g crystal), and the final temperature is 293.15 K.