XRPD Pharmaceutical Development Utilization Blog Series Part 1: From Solubility to Efficacy: Improving Drug Bioavailability through Powder X-ray Diffraction

by Kuniaki Kaburagi, Friday, 2nd December 2022

Over the next 4 installments, we will introduce a blog series on the utilization of powder X-ray diffraction (XRPD), one of the solid-state analyses, in optimizing solubility and performance in pharmaceutical development.

In this first installment, we will focus on how the application of XRPD helps achieve the Quality Target Product Profile (QTPP), required to prove that a pharmaceutical product meets “all the conditions.” For other installments, please refer to Part 2, Part 3, and Part 4.

Challenges of Low Drug Solubility in Pharmaceutical Development

To ensure that low molecular weight drugs have the correct bioavailability, it is crucial to ensure the desirable solubility of the active pharmaceutical ingredient (API). However, drug solubility poses significant challenges in pharmaceutical development. Approximately 75% of developing drugs are poorly soluble, which can significantly impact the efficacy of innovative new therapies.

To enhance the efficacy of these products, researchers work to optimize the solubility of APIs. This requires solid-state analysis to identify the various crystalline, amorphous, salt, and solvate forms of the compounds and elucidate their properties. Solid-state analysis enables a clear understanding of the API and all its forms, allowing for the optimization and control of manufacturability and bioavailability. This can improve the effectiveness and safety of pharmaceuticals and enhance the likelihood of regulatory approval and clinical success.

An example of solid-state analysis is the use of powder X-ray diffraction (XRPD). Here, we explain how XRPD can be leveraged in pharmaceutical development and improvement, with a particular focus on achieving pharmaceutical quality standards.

What is XRPD?

XRPD is a rapid analysis technique primarily used for phase identification of crystalline materials. It detects the X-ray diffraction pattern of analytes, providing information on unit dimensions and ratios. XRPD is used to evaluate the amorphousness or crystallinity of APIs and to assess characteristics such as physical stability, manufacturability, and solubility in vivo.

Achieving Quality Target Product Profile (QTPP) with XRPD

XRPD can provide a detailed fingerprint of the crystal size and fine structure of APIs in dosage forms. This technology enables the evaluation of the solid forms of APIs and helps understand how this affects solubility and stability in various forms. For example, detailed information on the polymorphs of APIs assists in predicting the pharmaceutical safety, performance, and efficacy. XRPD is used to measure critical material attributes (CMA) required to demonstrate QTPP. QTPP considers the route of administration, dosage form, and bioavailability related to quality, safety, and efficacy.

The latest XRPD solid sample analysis technology provides the evidence needed to define critical quality attributes (CQA) that support QTPP, enabling:

  • Selection of APIs with higher solubility
  • Choice of stable forms with enhanced manufacturability and storability
  • Identification and elimination of polymorphs that could compromise drug efficacy and safety
  • Investigation of solid substitutes (polymorphs, salts, co-crystals, etc.)
  • Identification and patent acquisition of all relevant polymorphs

The collection of these physicochemical data is essential at multiple stages of the pharmaceutical development process. The solubility and stability of APIs are continually needed as APIs progress from early development stages through to clinical stages and the approval process. XRPD is the optimal technology to monitor these.

XRPD is a powerful tool for establishing, confirming, and optimizing the CMAs of pharmaceuticals. It detects and predicts changes in drug solubility and stability. This provides key information throughout the drug development process, from the concept phase to the manufacturing stage.

In the next blog, we will discuss how understanding the presence of polymorphs in pharmaceuticals can lead to patient benefits and intellectual property protection.

For those who would like to learn more about how XRPD can be utilized in pharmaceutical development, please download the FULL guide.

Click here for the FULL guide

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