Related Experiment Video
Updated: Jun 27, 2026
11:27
A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
The stability and dissolution properties of solid glucagon/gamma-cyclodextrin powder
Laura Matilainen1, Sirkka Liisa Maunu, Jari Pajander
1Department of Pharmaceutical Chemistry, University of Kuopio, P.O.Box 1627, FIN-70211 Kuopio, Finland.
Summary
Glucagon/gamma-cyclodextrin powder shows superior solid-state stability and dissolution compared to glucagon/lactose. Gamma-cyclodextrin enhances glucagon
Area of Science:
- Pharmaceutical Science
- Solid-State Chemistry
- Drug Formulation
Background:
- Glucagon stability is critical for therapeutic efficacy.
- Excipients like cyclodextrins and lactose are used in glucagon formulations.
- Understanding solid-state interactions and dissolution is key to drug development.
Purpose of the Study:
- To evaluate the solid-state stability and dissolution of glucagon/gamma-cyclodextrin and glucagon/lactose powders.
- To compare the protective effects of gamma-cyclodextrin versus lactose on glucagon.
- To assess the impact of excipients on glucagon degradation pathways and dissolution profiles.
Main Methods:
- Solid-state stability testing under accelerated conditions (temperature/humidity).
- Analysis using High-Performance Liquid Chromatography (HPLC), Mass Spectrometry (MS), Size-Exclusion Chromatography (SEC), turbidity, and Fourier Transform Infrared Spectroscopy (FTIR).
- Dissolution studies at various pH values (2.5, 5.0, 7.0) and solid-state Nuclear Magnetic Resonance (NMR) spectroscopy.
Main Results:
- Glucagon degraded via oxidation and aggregation in solid state; Maillard reaction occurred with lactose.
- Glucagon/gamma-cyclodextrin exhibited better solid-state stability than glucagon/lactose.
- Gamma-cyclodextrin improved glucagon dissolution at pH 5.0 and 7.0 and delayed post-dissolution aggregation.
Conclusions:
- Glucagon/gamma-cyclodextrin powder demonstrates enhanced solid-state stability and improved dissolution characteristics compared to glucagon/lactose.
- Gamma-cyclodextrin is a promising excipient for stabilizing glucagon and optimizing its release profile.
- CPMAS NMR could not confirm inclusion complex formation in the solid state, suggesting other stabilization mechanisms.
Related Concept Videos
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
01:24Glucagon-like Receptor Agonists
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.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
02:30Stability of Substituted Cyclohexanes
This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...