Related Experiment Video
Updated: Apr 10, 2026
12:38
Crystallization of Proteins on Chip by Microdialysis for In Situ X-ray Diffraction Studies
Published on: April 11, 2021
7.2K
Mapping the solid-state properties of crystalline lysozyme during pharmaceutical unit-operations
Mohammad Amin Mohammad1, Ian M Grimsey2, Robert T Forbes2
1Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK; Faculty of Pharmacy, University of Damascus, Damascus, Syria; School of Pharmacy, University of Bradford, Bradford BD7 1DP, UK.
Journal of Pharmaceutical and Biomedical Analysis
|June 13, 2015
Summary
Solid-state transformations of protein crystals, like lysozyme, are crucial for drug delivery. Milling can induce denaturation, but surprisingly, lysozyme
Area of Science:
- Biopharmaceutical industry
- Solid-state chemistry
- Protein crystallization
Background:
- Protein crystallization is key for controlled drug delivery.
- Biotherapeutic molecules exhibit complex solid-state properties and transitions.
- Lysozyme crystals serve as a model to study these transformations.
Purpose of the Study:
- To investigate solid-state transformations in protein crystals.
- To understand the effects of drying and milling on lysozyme crystal properties.
- To explore the relationship between structure, denaturation, and biological activity.
Main Methods:
- Differential scanning calorimetry (DSC) for thermal analysis.
- X-ray powder diffraction (XRPD) for crystallinity assessment.
- FT-Raman spectroscopy for structural analysis.
- Enzymatic assays to determine biological activity.
Main Results:
- Crystalline lysozyme exhibits a lower denaturation temperature (Tm) than amorphous lysozyme.
- Milling induces solid-state denaturation, primarily via an amorphous intermediate.
- Drying did not lead to amorphization; milling time critically influenced transformations.
- Mechanical denaturation did not impact the biological activity of dissolved lysozyme.
Conclusions:
- DSC is a vital tool for quantitatively monitoring solid-state transformations in protein crystals.
- Understanding these transformations is essential for optimizing protein-based drug delivery systems.
- Lysozyme's biological activity is robust against mechanical denaturation.
Related Concept Videos
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
858
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...
858
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
777
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...
777
01:29The Colloidal State
155
The formation of a colloidal system is exemplified by an aqueous solution containing Cl− ions is introduced to another containing Ag+ ions, resulting in the precipitation of solid AgCl as extremely tiny crystals. Instead of settling out as a filterable precipitate, these crystals remain suspended in the liquid, showcasing a colloidal system.A colloidal system involves colloidal particles within the approximate range of 1 to 1000 nm in at least one dimension, dispersed in a medium called...
155
01:10Recrystallization: Solid–Solution Equilibria
4.7K
Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...
4.7K
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
221
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
221
01:32Tissue Homogenization and Cell Lysis
11.6K
Tissue homogenization involves disintegrating tissue architecture and lysing cells, and is an early step in isolating and analyzing cellular components. The method used for homogenization depends on the sample type, the amount of sample available, the analyte to be obtained, and the sensitivity of the method. These methods are broadly classified as mechanical and non-mechanical methods.
Mechanical methods of tissue homogenization
These methods rely on applying external physical force to disrupt...
Mechanical methods of tissue homogenization
These methods rely on applying external physical force to disrupt...
11.6K