Sulfonylureas: Physico-chemical Properties, Analytical Methods of Determination and Bioavailability
Oral antidiabetic drugs are widely used in the treatment of diabetes mellitus and are effective in controlling blood glucose levels. These drugs are of several distinct types with different modes of action and include sulfonylureas, biguanides and α-gluco
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Sulfonylureas: Physico-chemical Properties, Analytical Methods of Determination and Bioavailability S.L.
ALl, H.H.
BLUME, AND B.S. SCHUG
A. Introduction Oral antidiabetic drugs are widely used in the treatment of diabetes mellitus and are effective in controlling blood glucose levels. These drugs are of several distinct types with different modes of action and include sulfonylureas, biguanides and a-glucosidase inhibitors. The sulfonylurea antidiabetic drugs include acetohexamide, acetylcarbutamide, carboxytolbutamide, carbutamide, chlorpropamide, glibenclamide, glibornuride, gliclazide, glimepiride, glipizide, gliquidone, glisoxepide, metahexamide, tolazamide and tolbutamide. The structural formulas of some of the important antidiabetic agents are given in Fig. 1.
B. Physical Properties I. Description Carbutamide is a white or almost white fine crystalline powder without smell. Chlorpropamide is a white, crystalline, odorless, tasteless powder. Glibenclamide is a white crystalline odorless powder. Gliclazide is a crystalli ne solid, glipizide is a white powder and gliquidone is a white or slightly yellow crystalline substance. Glimepiride is a white odorless crytalline powder (HOECHST 1994, personal communication). Glisoxepide is a white or slightly yellow crystaIline odorless powder (BAYER 1994, personal communication). Tolazamide is a crytalline powder and tolbutamide is an almost odorless, white, crystalline powder.
11. Melting Point Table 1 shows the meIting points of a number of sulfonylureas.
111. Solubility The solubility of the sulfonylurea compounds is influenced by the lipophilic character of the phenyl group and its substituents and by the hydrophilie properties of the SOrNH-CO-N group. The aliphatic substituents of the J. Kuhlmann et al. (eds.), Oral Antidiabetics © Springer-Verlag Berlin Heidelberg 1996
74 Ac.etohexamide
S.L. ALl et al.
O~C-O' f\S-NH-C-NH-Q
H 3C/
C"H",N,O.S
-
11
00
0
324.'12
Ca~boxytolbuta~ide
C"H"N,O,S 3DJ,OO
Carbutamide C"H\,N 3 0:!S 271.35
Chlorpropamide C'OH'3CIN203S
276.75
Cl Glibenclamide C"H..,ClN,O,S
4S4.OJ
Glibornuride
0
QCO-NH-CH 2- CH 2 OCH 3
eH
365.'8
Fig. 1. Structural formulas of important antidiabetic agents
S02-NH-CO-NH-Q
Sulfonylureas: Physico-chemical Properties
75
Gliclazide C"H"N,.O,S 323.42
Glipizide C"H"N,O.S 445.55
Gliquidone
Tolazamide C,.H 2 ,N J OJ S
311,41
Tolbutamide C'7 H'b hJ .. OJS
270,34
Glirnepiride C,.H"N.O,S 49J.62
Glisoxepide
H3C~ , 1 '\ . ~h ~ 11\.1" .\,.-C;1~-CH20 S02-I~H-C-NH-N~ I1 C il 0 o 0 -
C;:ll-!:~N~O~S
449.54
Fig. 1. Continued
S.L. ALl et al.
76 Table 1. Melting points of a number of sulfonylureas Substance
Melting point (0C)
Reference
Acetohexamide Acetykarbutamide Carboxytolbutamide Carbutamide
183-185 188-190 187-189 211 139-142
Chlorpropamide
About 128
Glibenclamide
127-129 169-174 About 173
Glibornuride Gliclazide Glimepiride
186-189 About 181 About 207
Glipizide Gliquidone Glisoxepide Metahexamide Phenbutamide Tolazamide
About 205 About 178 192-198 151-152 130-132 161-169
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