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Insulin Formulations: Types and Delivery01:27

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Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
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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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Insulin: Biosynthesis, Chemistry, and Preparation01:25

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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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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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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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Oral Hypoglycemic Agents: Sulfonylureas01:17

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Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
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pH-Sensitive oral insulin delivery systems using Eudragit microspheres.

Raghavendra C Mundargi1, Vidhya Rangaswamy, Tejraj M Aminabhavi

  • 1Reliance Life Sciences, Industrial Biotechnology, Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, India.

Drug Development and Industrial Pharmacy
|March 23, 2011
PubMed
Summary
This summary is machine-generated.

pH-sensitive Eudragit L100 microspheres effectively deliver insulin orally. These microspheres protect insulin in the stomach and release it in the intestine, showing significant glucose reduction in diabetic rats.

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Area of Science:

  • Pharmaceutical Sciences
  • Biomaterials Science

Background:

  • Oral delivery of insulin is challenging due to degradation in the gastrointestinal tract.
  • pH-sensitive polymers offer a potential solution for targeted drug release.

Purpose of the Study:

  • To develop and evaluate pH-sensitive Eudragit L100 microspheres for oral insulin delivery.
  • To assess the in vitro and in vivo performance of insulin-loaded microspheres.

Main Methods:

  • Microspheres prepared using the double emulsion-solvent evaporation technique.
  • In vitro release studies conducted at pH 1.2 and pH 7.4.
  • Characterization using scanning electron microscopy and circular dichroism.
  • In vivo studies on diabetic-induced rat models.

Main Results:

  • Eudragit L100 microspheres showed no insulin release at pH 1.2 but maximum release at pH 7.4 within 4-6 hours.
  • Microsphere size ranged from 1 to 40 μm.
  • Insulin structural integrity was maintained during encapsulation and release.
  • In vivo studies demonstrated up to 86% inhibition in diabetic rats, indicating intestinal absorption.

Conclusions:

  • Eudragit L100 microspheres are a promising system for oral insulin delivery.
  • The pH-sensitive nature of the microspheres ensures targeted release in the intestine.
  • This approach holds potential for improving insulin therapy in diabetic patients.