A thorough understanding of the solid state properties of drugs is vital for pharma companies that want to develop effective pharmaceuticals. These properties affect how stable, soluble, and bioavailable a drug will be.
In essence, a good grasp of how active pharmaceutical ingredients (APIs) behave in their solid form is important for making effective drugs. In this guide, we explore key aspects of solid state properties that impact drug development.
What Are Solid-State Properties?
The solid-state properties of a drug substance directly affect how well it lasts, how easily it dissolves, and how well the body absorbs it. A clear understanding of these properties helps pharmaceutical companies develop effective formulations while ensuring the drug’s physical and chemical stability.
Crystallinity
Crystallinity is when molecules in a solid are arranged in a regular pattern. This pattern can affect how well the substance lasts and how easily it dissolves. Crystallinity is often used in medicines because it makes them more stable and easier to work with during development.
Polymorphism
Polymorphism occurs when a compound can form different crystal structures that all have distinct properties. This phenomenon is common among small-molecule drugs, and research suggests that up to 51% of these compounds can exhibit polymorphism.
Polymorphs can display different mechanical, thermal, physical, and chemical properties, all of which affect how much of the drug is absorbed by the body (bioavailability) and how long it lasts (stability).
Amorphous Solids
Amorphous solids do not have a long-range ordered structure. While their structure can lead to higher solubility, studies show that these types of solids have lower stability compared to crystalline forms. It usually requires techniques like solid dispersions with polymers to stabilize amorphous solids.
Types of Solid-State Forms
Solvates and Hydrates
Solvates are types of crystals that have solvent molecules mixed in. Hydrates are a special kind of solvate where water is the solvent. These forms can change how well a drug dissolves and how long it lasts.
Salts
Salts are made by mixing the drug ingredient with an acid or a base. This changes important features, such as how easily they dissolve and how long they stay effective. Because of this, salts are commonly used in pharmaceuticals. Studies estimate that about half of all FDA-approved drugs use APIs in salt form because they work better.
Cocrystals
Cocrystals are made by combining the drug ingredient with another molecule. This can change how the drug works. These solid-state forms are known for making drugs work better.
Understanding Solid-State Properties
To learn more about the solid-state properties of drugs, scientists use different tools and methods. These tools help them correctly identify and study the properties of pharmaceutical materials. Some of the most common methods they use include:
Powder X-Ray Diffraction
This tool helps identify the different forms of drug ingredients, such as how the molecules are arranged. It differentiates between materials that have a regular structure (by their diffraction patterns) and those that do not. This is important for making drugs and keeping them stable.
Infrared (IR) and Raman Spectroscopy
These tools offer insights into how the molecules in drugs are arranged and how they interact with each other. They are often used with powder X-ray diffraction to identify important parts of the molecules and how they affect drug performance.
Solid-State Nuclear Magnetic Resonance (ssNMR)
ssNMR gives detailed information about how molecules are arranged in solids. It is especially helpful for complicated systems where other methods may not give enough detail. With this tool, researchers can make drug formulas better by understanding how molecules are arranged and how they interact.
Implications for Formulation Development
Impact on Bioavailability and Stability
A drug’s solid-state properties can significantly affect how well it dissolves and how long it stays stable. Different solid forms may break down at different rates or have varying solubility, which directly impacts how well the drug works in the body.
Role in Pharmaceutical Product Development
Solid-state properties affect the manufacturing process and final drug product quality. In the pharmaceutical industry, scientists use techniques like powder X-ray diffraction and differential scanning calorimetry to characterize these properties. Additionally, they rely on methods such as UV-Vis spectroscopy to analyze the drug’s solid form and support the development process.
Considerations for Formulation Development
During formulation development, pharma companies must consider factors such as particle size, surface area, and polymorphism to make sure the drugs perform optimally. These properties can affect how quickly the drug dissolves and how stable it is, which impacts its effectiveness.
Also, during preclinical drug development, a sound understanding of these properties can make it easier to meet regulatory requirements, such as those necessary for an IND filing. When pharma companies partner with a CDMO, they can leverage their expertise in characterization methods to make the development process more efficient.
Full-service CDMOs like Vici Health Sciences use techniques like diffraction, thermal analysis, and thermogravimetric analysis to ensure optimal formulation and manufacturing of the drug product.
Partner With Vici Health Sciences to Improve Your Drug Formulations
Pharmaceutical companies face many challenges in drug development, and understanding solid-state properties is important if they are to create effective and reliable products.
Partnering with Vici Health Sciences gives you access to our expertise in formulation development, analytical method validation, and manufacturing process optimization. Our experienced team supports you at every stage—from early R&D to FDA approval—to make sure your drug products meet the highest standards of quality and efficacy.
Contact us today to discover how we can help you achieve your drug development goals.
