The Physico-Chemical Properties of Glipizide: New Findings

Abstract

The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.

Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status

“…Diabetic foot ulcer a serious problem resulting from unregulated diabetes, causing significant sickness and death rates [8]. Beyond its primary action on the pancreas, glipizide has been found to enhance insulin sensitivity and decrease hepatic glucose synthesis [9].…”

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“…Besides, GPZ can increase insulin sensitivity and diminish hepatic glucose production through indirect extrapancreatic effects related to hepatic glycogen metabolism, gluconeogenesis, and lipogenesis 17,18 .…”

Opportunities and challenges of incretins-based hypoglycemic agents treating of T2DM from the insight of physiological disposition

“…Among them, drug treatment is the most widely used and efficiency method in treating diabetes. There has already been a series of drugs, including insulin stimulating agents which promote releasing of insulin through interaction with specific receptor (Bruni et al, 2021); Metformin type agents which have the ability to suppress hepatic glucose production (Foretz et al, 2019); Thiazolidinediones type agents which reduce insulin resistance via rising disposal insulin-dependent glucose and reducing the production of hepatic glucose (Saltiel & Olefsky, 1996); α-glucosidase inhibitors which could competitively inhibit α-glucosidase and cause delayed glucose absorption in small intestine (Hossain et al, 2020); Insulin, used in diabetes treatment for decades, itself has the ability to regulate blood glucose (Mann et al, 2020); Insulin analogues which modulate the ability of insulin to control blood glucose level (Andersen et al, 2021) and incretins-based hypoglycemic agents which stimulate insulin secretion from β cells (Chia & Egan, 2020).…”