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Questions and Answers
Acicular is a type of crystal habit.
Acicular is a type of crystal habit.
True
Spironolactone has 3 polymorphs.
Spironolactone has 3 polymorphs.
False
Phenobarbitone has been found to have 10 crystal modifications.
Phenobarbitone has been found to have 10 crystal modifications.
False
Approximately 70% of barbiturates exhibit polymorphism.
Approximately 70% of barbiturates exhibit polymorphism.
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Crystal habit differences can cause problems in tableting and suspensions.
Crystal habit differences can cause problems in tableting and suspensions.
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The polymorph with the highest free energy is generally the most stable.
The polymorph with the highest free energy is generally the most stable.
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Phase changes in suspensions may lead to changes in crystal size.
Phase changes in suspensions may lead to changes in crystal size.
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In FTIR, the sample is blended with NaCl to make a disc.
In FTIR, the sample is blended with NaCl to make a disc.
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Polymorphism occurs when molecules rearrange themselves in only one way within the crystal lattice.
Polymorphism occurs when molecules rearrange themselves in only one way within the crystal lattice.
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Crystal habits always have different internal structures and different XRD patterns.
Crystal habits always have different internal structures and different XRD patterns.
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Powder X-ray Diffractometry (PXRD) is the ultimate method for phase identification.
Powder X-ray Diffractometry (PXRD) is the ultimate method for phase identification.
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X-ray diffraction is used to measure the average spacings between layers or rows of atoms.
X-ray diffraction is used to measure the average spacings between layers or rows of atoms.
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According to the Bragg equation, the angle of incidence of X-ray beams, denoted by theta ($θ$), is used in a mathematical relationship to explain X-ray reflection by crystals.
According to the Bragg equation, the angle of incidence of X-ray beams, denoted by theta ($θ$), is used in a mathematical relationship to explain X-ray reflection by crystals.
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XRD diffraction patterns can distinguish between polymorphs, but cannot determine the orientation of a single crystal.
XRD diffraction patterns can distinguish between polymorphs, but cannot determine the orientation of a single crystal.
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The Bragg relationship was developed in 1931 by English physicists Sir W.H. Bragg and his son, Sir W.L. Bragg.
The Bragg relationship was developed in 1931 by English physicists Sir W.H. Bragg and his son, Sir W.L. Bragg.
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Liquid and amorphous samples produce a discrete and sharp peak pattern in XRD analysis.
Liquid and amorphous samples produce a discrete and sharp peak pattern in XRD analysis.
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Changes in spectra can occur when a crystalline substance converts to an amorphous form.
Changes in spectra can occur when a crystalline substance converts to an amorphous form.
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Solvent extraction methods for drug isolation do not influence the crystal form.
Solvent extraction methods for drug isolation do not influence the crystal form.
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Cortisone has only 3 known crystal forms.
Cortisone has only 3 known crystal forms.
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Re-crystallization from the same solvent can convert samples into same forms.
Re-crystallization from the same solvent can convert samples into same forms.
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The most stable polymorph of a drug typically has the highest solubility.
The most stable polymorph of a drug typically has the highest solubility.
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Grinding digoxin will cause formation of a stable crystal.
Grinding digoxin will cause formation of a stable crystal.
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Form B of chloramphenicol has a lower biological activity than Form A.
Form B of chloramphenicol has a lower biological activity than Form A.
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In development of dosage, the physical state of the drug is irrelevant during toxicity studies.
In development of dosage, the physical state of the drug is irrelevant during toxicity studies.
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In the equation $nλ=2d sin θ$, 'd' represents the diameter of the crystal.
In the equation $nλ=2d sin θ$, 'd' represents the diameter of the crystal.
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X-ray diffraction (XRD) provides direct evidence for the periodic atomic structure of crystals.
X-ray diffraction (XRD) provides direct evidence for the periodic atomic structure of crystals.
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Differential Scanning Calorimetry (DSC) provides detailed information of the nature of phase transitions.
Differential Scanning Calorimetry (DSC) provides detailed information of the nature of phase transitions.
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Thermogravimetric Analysis (TGA) gives qualitative information on the stoichiometry of solvates and hydrates.
Thermogravimetric Analysis (TGA) gives qualitative information on the stoichiometry of solvates and hydrates.
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Polymorphs of a substance can have different melting points.
Polymorphs of a substance can have different melting points.
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Gout is caused by the accumulation of monosodium urate crystals in the joints.
Gout is caused by the accumulation of monosodium urate crystals in the joints.
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Kidney stones are formed from concentrated substances such as calcium, oxalate and saline.
Kidney stones are formed from concentrated substances such as calcium, oxalate and saline.
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Amyloidosis is characterized by the formation of needle-like crystals in various organs.
Amyloidosis is characterized by the formation of needle-like crystals in various organs.
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The level of uric acid in the articular cartilage needs to exceed 9.7 mg/dL to form crystals.
The level of uric acid in the articular cartilage needs to exceed 9.7 mg/dL to form crystals.
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Gout typically causes intense pain and swelling mainly in the wrist.
Gout typically causes intense pain and swelling mainly in the wrist.
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Kidney stones can cause severe pain when they travel through the digestive system.
Kidney stones can cause severe pain when they travel through the digestive system.
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Amyloid deposits in amyloidosis disrupt the normal function of affected organs such as the liver and heart.
Amyloid deposits in amyloidosis disrupt the normal function of affected organs such as the liver and heart.
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High levels of calcium in the blood assist in the formation of gout.
High levels of calcium in the blood assist in the formation of gout.
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Study Notes
Polymorphism and its Clinical Implications
- Polymorphism is a phenomenon where a compound can exist in multiple crystal structures, each with unique physical and chemical properties.
- Different crystal habits (external shapes) result from different crystal structures.
- Similar internal structure and XRD patterns can exist but lead to different properties between compounds.
- Compounds crystallize as different polymorphs depending on crystallization conditions.
Overview
- Polymorphism is defined as the ability of a substance to exist in multiple crystalline forms.
- The pharmaceutical and clinical implications of polymorphism are substantial, impacting drug stability, dissolution rate, bioavailability, and potential for adverse effects.
- Polymorphic forms have similar chemical composition but different crystal structures leading to differences in their physical and chemical properties.
Polymorphism Point to Understand
- Polymorphism means a substance existing in multiple crystalline forms.
- Polymorphs differ in physical traits but have the same chemical structure.
- Polymorphism is related to crystallization conditions.
Compounds
- Compounds crystallize out of differing solution habits depending on the conditions of crystallization.
- Crystal habits have comparable internal structures and XRD patterns.
- Compounds crystallize as different polymorphs influencing properties.
Analytical Techniques for Solid State Characterization
- Powder X-ray Diffractometry (PXRD) is a crucial technique for identifying crystalline phases.
- Single crystal XRD provides detailed structural information.
- XRD measures average atomic layer spacing.
- XRD is used to determine crystal structure.
- XRD establishes phase compositions and material properties.
- XRD differentiates polymorphs by their distinct diffraction patterns.
Why XRD?
- Measures average interatomic distances
- Determines crystal orientation
- Identifies unknown materials
- Establishes phase composition & material properties
- Differentiates polymorphs.
95% of all solid materials are crystalline
- When X-rays interact with a crystalline substance, diffraction patterns are created.
- The diffraction patterns reveal the crystalline structure.
X-ray Diffraction (XRD)
- Sir Bragg related X-ray beams at particular angles to crystal faces.
- Bragg's Law (nλ = 2d sin θ) relates wavelength, angle, and spacing between atomic layers.
Variables in Bragg's Law
- d = distance between atomic layers
- λ = wavelength of incident X-ray beam
- θ = angle of incidence (Bragg's angle)
- n = integer
Pharmaceutical Implications of Polymorphism
- Problems in tableting and injections can stem from differences in crystal habits, influencing processing.
- Polymorphs have distinct properties, impacting stability and biopharmaceutical behavior.
- The most stable polymorphic form has the lowest free energy.
Differential Scanning Calorimetry (DSC)
- DSC measures the heat flow during phase transitions, identifying crystalline forms and interactions with excipients.
- "Black box" technique, providing no information about the transition's essential nature.
Thermogravimetric Analysis (TGA)
- TGA measures weight changes during heating determining the stoichiometry of solvates/hydrates.
- Interferences occur due to water-containing excipients.
Polymorphs and different properties
- Polymorphs display different physical and chemical characteristics (e.g., melting point, solubility).
- Different crystal habits (external appearances) are observed in various polymorphs.
Spironolactone Polymorphic Forms
- Polymorphic forms of spironolactone display different crystal structures yielding different properties, such as melting points.
- The production process, crystal form, melting point and axes (nm) for both Form 1 and Form 2 are compared.
Paracetamol Polymorphic Forms
- Two crystalline forms of paracetamol (PCM) exist—Form I and Form II—differing in properties and physical behavior.
- Form I is plate-like, more stable and less suitable for direct compression, while Form II is prism-like and less stable, readily undergoing plastic deformation under compaction.
Phenobarbitone and Barbiturates
- Phenobarbitone exists in multiple crystalline forms.
- Barbiturates (e.g. various forms of a given compound) exhibit polymorphic characteristics.
Polymorphic Drugs and Their Characteristics
- Various drugs exhibit polymorphic and pseudopolymorphic forms influencing properties such as solubility and melting points.
- Drugs exhibit a wide variety of polymorphic and pseudopolymorphic forms.
Crystal Solvate and Pseudopolymorphic Solvates
- Crystalline solvates contain solvent molecules within their crystal structure, influencing properties.
- Pseudo-polymorphic solvates merely occupy crystal voids.
Polymorphic Transformations
- Transformations between polymorphic forms can cause issues in drug formulations; for example, the formation of caked powders.
Analytical Issues and Consequences
- Infrared spectroscopy (FTIR), in particular, demonstrates variation in spectra for different polymorphs.
- Polymorphic considerations in drug formulations are essential.
- Differences in polymorphs are significant concerning bioavailability.
- Polymorphic differences can influence drug stability, and dissolution rates, hence affecting the treatment efficacy.
Clinical Examples and Impact on Treatment
- Gout arises from uric acid crystal accumulation causing joint inflammation and pain.
- Kidney stones are crystalline formations comprising minerals, oxalates, and uric acid contributing to urinary tract discomfort.
- Amyloidosis involves abnormal proteins accumulating in organs, impacting organ functions.
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Description
This quiz explores the concept of polymorphism, focusing on its significance in pharmaceuticals and clinical settings. Understand how different crystalline forms of compounds affect drug properties such as stability, dissolution rate, and bioavailability. Dive into the implications of polymorphism on drug development and patient safety.
