What is the Difference Between Polymorphism and Pseudopolymorphism

The main difference between polymorphism and pseudopolymorphism is that polymorphism is the existence of multiple crystalline forms of a substance, each with distinct arrangements of molecules or atoms within its crystal lattice, while pseudopolymorphism is the existence multiple crystalline forms of a substance due to changes in external conditions or solvents, rather than variations in molecular packing.

Polymorphism and pseudopolymorphism are phenomena related to the different crystalline forms a substance can take, but they arise from distinct causes and mechanisms.

Key Areas Covered

1. What is Polymorphism 
     – Definition, Cause, Stability 
2. What is Pseudopolymorphism
     – Definition, Cause, Stability 
3. Similarities Between Polymorphism and Pseudopolymorphism
     – Outline of Common Features
4. Difference Between Polymorphism and Pseudopolymorphism
    – Comparison of Key Differences

Key Terms

Polymorphism, Pseudopolymorphism

Difference Between Polymorphism and Pseudopolymorphism - Comparison Summary

What is Polymorphism

Polymorphism refers to the capacity of a substance to exist in multiple crystalline forms, each with distinct properties and characteristics. While chemical composition remains constant, the arrangement of these constituent entities can undergo significant changes, giving rise to an array of polymorphs, each resembling a different facet of the substance’s identity. The polymorphic forms possess their own unique structures, often resulting in different macroscopic properties, such as solubility, melting point, hardness, and even optical characteristics.

The existence of polymorphism challenges our conventional understanding of solids as fixed entities with well-defined properties. Instead, it reveals the dynamic nature of matter, showing how multiple configurations can coexist within the same chemical structure. This variability has notable effects on industries that rely on consistent material properties, especially pharmaceuticals. In this context, polymorphism can significantly affect drug efficacy and stability.

Compare - Polymorphism vs Pseudopolymorphism

The pharmaceutical industry, particularly, has a keen interest in polymorphism due to its potential impact on drug development and formulation. Different polymorphs of a drug molecule can exhibit varying solubilities, dissolution rates, and bioavailabilities, directly influencing a drug’s efficacy and safety profile. The presence of polymorphic forms in pharmaceutical products can lead to inconsistent therapeutic outcomes, emphasizing the importance of thorough polymorph screening during drug development. In some cases, the choice of a specific polymorph can be the difference between a successful drug and a market failure.

What is Pseudopolymorphism

Pseudopolymorphism involves the appearance of different crystalline forms of a substance, driven not by variations in molecular arrangement but rather by shifts in external conditions or solvents. This intriguing concept offers valuable insights into the delicate balance between thermodynamics, kinetics, and the transformative power of the environment.

Unlike true polymorphs that arise from distinct molecular arrangements within a crystal lattice, pseudo polymorphs form through temporary interactions between the substance and its environment. These interactions result in crystalline structures that can take on separate forms under specific conditions but often revert to a single stable form when those conditions shift.

A classic example of pseudopolymorphism involves the anhydrous and hydrated forms of certain salts. These salts can crystallize with water molecules incorporated into their lattice structures, leading to the formation of hydrates. The presence or absence of water molecules results in distinct pseudopolymorphic forms that exhibit different physical properties, such as color, solubility, and stability. However, the seemingly distinct forms can be illusory; changes in temperature or humidity can cause the hydrated form to release water molecules and transition back to the anhydrous form, highlighting the reversible nature of pseudopolymorphism.

Study and Applications of Pseudopolymorphism

The study of pseudopolymorphism requires sophisticated analytical techniques to unravel the intricate interplay between molecular interactions and environmental conditions. Differential scanning calorimetry (DSC), for example, measures the heat flow associated with phase transitions, offering insights into the energy changes that occur as a substance undergoes pseudopolymorphic transformations. X-ray diffraction, another essential tool, allows researchers to examine the structural changes that accompany pseudopolymorphism, shedding light on the transient nature of the different forms.

Pseudopolymorphism holds notable importance in the pharmaceutical field, especially for drugs in solid forms like tablets and capsules. These drugs can show pseudopolymorphic traits when subjected to varying humidity or temperature during production and storage. These changes influence dissolution rate, bioavailability, and stability, directly impacting the drug’s effectiveness. The reversibility of pseudopolymorphism complicates formulation and manufacturing, requiring meticulous control of environmental conditions to maintain consistent drug performance over time.

The presence of pseudopolymorphism calls for innovative strategies to mitigate its effects. One approach involves the use of desiccants or humidity control during pharmaceutical manufacturing and packaging to minimize the chance of pseudopolymorphic transitions. Additionally, techniques such as spray drying, which involves atomizing a solution of the drug and drying it rapidly, can create amorphous forms of the drug that are less prone to pseudopolymorphism due to their lack of a defined crystalline structure.

Similarities Between Polymorphism and Pseudopolymorphism

  • Both polymorphism and pseudopolymorphism involve the existence of multiple forms of a substance.
  • In both cases, different forms can exhibit variations in their molecular or atomic arrangements within the crystal lattice. These variations lead to differences in physical properties, such as melting point, solubility, and optical characteristics.
  • Both polymorphism and pseudopolymorphism are influenced by thermodynamic principles.
  • Both concepts have significant implications in the pharmaceutical industry.

Difference Between Polymorphism and Pseudopolymorphism


Polymorphism refers to the existence of multiple crystalline forms of a substance, each with distinct arrangements of molecules or atoms within its crystal lattice. On the other hand, pseudopolymorphism refers to the appearance of different crystalline forms of a substance due to changes in external conditions or solvents rather than variations in molecular packing.


Polymorphism occurs due to variations in the arrangement of molecules within a crystal lattice, while pseudo-polymorphism arises from shifts in external conditions or solvents rather than changes in the molecular arrangement. The crystalline forms in pseudopolymorphism are a result of transient interactions between the substance and its environment.


True polymorphs are stable under specific conditions, each with its own distinct energy minimum and physical properties. However, pseudo-polymorphic forms are often less stable and can be influenced by changes in factors like temperature, humidity, or solvent composition.


In brief, polymorphism is driven by changes in internal molecular arrangement, leading to stable variations in crystal forms, while pseudopolymorphism is a result of temporary interactions with the environment or solvents, causing reversible changes in crystalline forms.


1. “Polymorphism – Definition, Types, Importance and Applications of Polymorphism.” Byju’s.
2. “Pseudopolymorphs in Industrial Use.” Research Gate.

Image Courtesy:

1. “ROY polymorphs” By Michael J Hall, Michael R Probert et al. – NCBI. (CC BY-SA 4.0) via Commons Wikimedia

About the Author: Hasini A

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