Chitosan Loaded Mucoadhesive Microspheres of Gliclazide - Journal

Fig. No-2: HPLC chromatogram of [GKRA-13]
E-isomer= 94.07 % ; Z-isomer= 5.84 %
Z- isomer
Gopal Krishna Rao et al./ Effect of Different Acids on the Formation of E and Z Isomers of Dothiepin
E- isomer
Fig 3: General method for Calculation of percentage
1
of isomers using H-NMR spectrum
1
The H-NMR spectral analysis also revealed the formation
of the E- and Z- isomers, N,N-dimethyl-3-
(dibenzo[b,e]thiepin-11(6H) ylidene)propylamine at δ value
5.90 and 5.83 respectively in all the experiments. General
method of calculation of E and Z isomers using NMR
technique is depicted in( Fig. 3).
Further confirmation was done by HPLC, which showed
formation of E-isomer in the range of 89-94 % whereas Zisomer
formation was in the range of 6-10 % for dothiepin
Table 2.
Table 1: Data of Percentage Yield, Melting Point of Dothiepin with various acids
Sl. No. Compound Acid Prac. Yield % Yield M.P. (ºC)
1 GKRA-07 Maleic acid 7.5 g 80 220-222
2 GKRA-08 Oxalic acid 7.8 g 83 218-220
3 GKRA-09 Tartaric acid L(+) 8.2 g 88 218-220
4 GKRA-10 Phosphoric acid 5.4 g 58 189-191 *
5 GKRA-11 Tartaric acid DL 5.5 g 60 198-200 *
6 GKRA-12 Indian Resin-220 7.4 g 79 186-188 *
7 GKRA-13 p- Toluyl sulphonic acid 8.7 g 92 218-220
* Formation of isomers and separation was not possible in these cases.
Table 2: Percentage of Dothiepin isomers evaluated by 1 H-NMR and High Performance Liquid
Chromatography.
Sl. No. Compound Acid used E:Z ( 1 H-NMR) E:Z (HPLC)
1 GKRA-07 Maleic acid 85:15 92:8
2 GKRA-08 Oxalic acid 85.3:14.7 92:8
3 GKRA-09 Tartaric acid L(+) 84:16 89:11
4 GKRA-10 Phosphoric acid *** ***
5 GKRA-11 T Tartaric acid DL *** ***
6 GKRA-12 Indian resin-220 *** ***
7 GKRA-13 p-Toluyl sulphonic acid 93:7 94.07:5.84
*** Formation of isomers and separation was not possible in these cases
174
RJPS, Jul - Sep, 2011/ Vol 1/ Issue 2