Cephalexin hydrate

Under the development of a sorption method of aminocephalosporin, isolation data on solubility are used for choice of the conditions for antibiotic desorption from a sorbent. For example, under desorption of cephalexin from nonionic sorbents high-concentrated eluates (120 g/l and more, regarding to anhydrous substance), suitable for following effective precipitation of cephalexin monohydrate, have to be produced. Possible pH values of eluates calculated on the basis of Eqs. 11 and 12 using data on antibiotic solubility from Table 1 are pH B 1.9 and pH C 8.1.

The phase change (melting) of cephalexin monohydrate was not typical when observed through the scope of a Melt-Temp apparatus. Neither 196–198 ℃ nor 326.8 ℃is the melting temperature of cephalexin BP, USP. More correctly, 196–198 ℃ is the decomposition temperature. Since pharmaceutical operations are frequently time courses, DSC and melting point study alone may not be sufficient to determine an optimal operation temperature in the required process time duration. Application of heat stress test on a drug of interest at different temperatures for different durations and then analyze with HPLC may be the best approach to identifying the safe operation temperature and process duration. It is advised that the results obtained from DSC, MEL-TEMP® apparatus, visual inspection and HPLC analysis should also be incorporated into a decision making. Small quantity of cephalexin monohydrate BP, USP may be degraded as early as 80 ℃ if the heating process is 90 min or greater. The results of this study suggested that the bound water in cephalexin is not just there to fill the voids in the crystal, but exhibits the interaction with the crystal structure. The evidences are (1) the UV and HPLC studies found that there was a [3% decomposition when cephalexin monohydrate was heated at 100 ℃ for 90 min (n = 7, Table 4d), (2) the MEL-TEMP apparatus identifies decomposition began at 98 ℃, small bubble formation occurred at 140–148 ℃(n = 8, Fig. 3b), and (3) DSC displayed a large sharp exothermic event (102.9 mJ mg^-1, n = 4. Table 1) from 173 to 208 ℃ with the apex temperature at 196.9 ℃(n = 6, Table 5).