Related Experiment Video
Updated: Jul 18, 2026
12:29
Optimization of Crystal Growth for Neutron Macromolecular Crystallography
Published on: March 13, 2021
Achieving polymorph selectivity in the crystallization of pharmaceutical solids: basic considerations and recent
1Pharmaceutical Sciences Research and Development, Eli Lilly & Co, Lilly Corporate Center, Indianapolis, IN 46285, USA. reutzel-edens_susan_m@lilly.com
Current Opinion in Drug Discovery & Development
|November 23, 2006
Summary
Controlling pharmaceutical crystal polymorphs is key for robust manufacturing. This review explores thermodynamic, kinetic, and molecular factors influencing crystal forms and their industrial control.
Area of Science:
- Pharmaceutical Science
- Chemical Engineering
- Materials Science
Background:
- Controlling crystal polymorphism is critical for pharmaceutical manufacturing.
- Understanding thermodynamic and kinetic factors is essential for reproducible crystallization.
- Molecular mechanisms of polymorph formation require further elucidation.
Purpose of the Study:
- To review thermodynamic and kinetic factors influencing pharmaceutical crystal polymorphism.
- To discuss recent advances in understanding the molecular mechanisms of polymorph appearance.
- To present case studies on applying process analytical technology in pharmaceutical crystallization.
Main Methods:
- Literature review of thermodynamic and kinetic principles.
- Analysis of molecular mechanisms governing crystal form.
- Case study analysis of process analytical technology (PAT) implementation.
Main Results:
- Identified key thermodynamic and kinetic parameters for polymorph control.
- Highlighted advances in understanding molecular-level crystallization processes.
- Demonstrated PAT's utility in managing polymorphism in pharmaceutical development.
Conclusions:
- Effective control of pharmaceutical crystal polymorphs relies on understanding thermodynamic, kinetic, and molecular factors.
- Process analytical technology offers powerful tools for managing complex crystallization processes.
- Continued research into molecular mechanisms will enhance robust pharmaceutical manufacturing.
Related Concept Videos
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...
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
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,...
01:10Recrystallization: Solid–Solution Equilibria
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...
01:25Crystal Growth: Principles of Crystallization
Crystallization is a phase transformation process in which crystals are precipitated from a supersaturated solution or formed from other sources. During crystallization, atoms or molecules arrange themselves into a well-defined, rigid crystal lattice to minimize energy.
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent – the...
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent – the...
01:21Polymer Classification: Crystallinity
Unlike ionic or small covalent molecules, polymers do not form crystalline solids due to the diffusion limitations of their long-chain structures. However, polymers contain microscopic crystalline domains separated by amorphous domains.
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
Crystalline domains are the regions where polymer chains are aligned in an orderly manner and held together in proximity by intermolecular forces. For example, chains in the crystalline domains of polyethylene and nylon are bound together by van der Waals...
01:26Polymer Classification: Stereospecificity
Polymerization generates chiral centers along the entire backbone of a polymer chain. Accordingly, the stereochemistry of the substituent group has a significant effect on polymer properties. Polymers formed from monosubstituted alkene monomers feature chiral carbons at every alternate position in the polymer backbone. Relative to the predominant orientation of substituents at the adjacent chiral carbons, the polymer can exist in three different configurations: isotactic, syndiotactic, and...