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Oral Hypoglycemic Agents: Glinides01:06

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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Insulin: Biosynthesis, Chemistry, and Preparation

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The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
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Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
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Glimepiride/hydroxypropyl-β-cyclodextrin inclusion compound: preparation, characterization, and evaluation.

Xin Quan1, Shurui Wang1, Jiamin Lu1

  • 1Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.

Drug Development and Industrial Pharmacy
|March 13, 2025
PubMed
Summary

This study enhanced glimepiride (GM) solubility and bioavailability using a hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion compound prepared by ball milling. The novel formulation significantly improved drug release and pharmacokinetic profiles.

Keywords:
Glimepiridebioavailabilityinclusion compoundmechanical ball millingsolubilitystability

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Physical Chemistry

Background:

  • Glimepiride (GM) exhibits poor solubility and bioavailability, limiting its therapeutic efficacy.
  • Developing advanced formulations is crucial for improving GM's oral administration and patient outcomes.

Purpose of the Study:

  • To prepare and characterize a glimepiride/hydroxypropyl-β-cyclodextrin (GM/HP-β-CD) inclusion compound using optimized ball milling.
  • To evaluate the in vitro and in vivo performance of the novel GM/HP-β-CD inclusion compound.

Main Methods:

  • Response surface methodology was employed to optimize ball milling parameters for GM/HP-β-CD inclusion compound formation.
  • Characterization involved powder x-ray diffraction, DSC, SEM, and FTIR; stability, in vitro dissolution, and in vivo pharmacokinetic studies were conducted.

Main Results:

  • Optimized ball milling yielded a stable GM/HP-β-CD inclusion compound with 20x higher solubility and 12.7x faster dissolution than GM.
  • In vivo studies demonstrated a 3.5x increase in maximum plasma concentration and significantly enhanced bioavailability, with a shortened Tmax.

Conclusions:

  • The GM/HP-β-CD inclusion compound prepared by ball milling shows improved solubility, dissolution, stability, and bioavailability.
  • This formulation holds potential for sustained-release glimepiride delivery, reducing dosing frequency and improving patient compliance.