From solubility to efficacy: how X-ray powder diffraction is improving drug bioavailability

In this four-part blog series, we explore how one type of solid form analysis – X-ray powder diffraction (XRPD) – is helping drug developers optimize the solubility and performance of drugs. We begin in this blog with a focus on how applying XRPD helps achieve the quality target product profiles (QTPPs) required to demonstrate that a drug ‘ticks all the boxes’.

The challenges of poor drug solubility in drug development

For a small molecule drug to have the correct bioavailability, ensuring the desired solubility of the active pharmaceutical ingredients (APIs) is crucial. However, drug solubility is a major challenge in drug development: around 75% of drugs in development are poorly soluble, which can severely impact the desired efficacy of new life-changing therapies.

In efforts to improve the efficacy of these products, researchers are working to optimize API solubility. This involves carrying out solid form analysis to identify and characterize the various crystalline, amorphous, salts and solvate forms of compounds. Solid form analysis helps provide a clear understanding of an API and all its forms, thus enabling its optimization and control for processability and bioavailability. In the bigger picture, this can improve the efficacy and safety of the drug product and improve its chances of regulatory approval and clinical success.

One of the leading ways to perform solid form analysis is with the use of X-ray powder diffraction (XRPD). Here, we discuss how XRPD helps develop and improve pharmaceutical formulations, with particular emphasis on achieving drug quality criteria.

What is XRPD?

XRPD is a rapid analytical technique primarily used for phase identification of crystalline materials. It detects the X-ray diffraction patterns of analytes, providing information about unit dimensions and proportions. XRPD can assess the amorphous or crystalline nature of the API, helping to evaluate properties like the physical stability and manufacturability of a drug, as well as its solubility in a biological system.

Hitting Quality Target Product Profiles (QTPPs) with XRPD

XRPD can provide a detailed fingerprint of the crystalline size and microstructure of APIs in a dosage form. The technique enables researchers to assess an API’s solid form, providing information about how this might affect its solubility and stability in different dosage forms. Detailed information about different polymorphs of an API, for example, can support predictions about the safety, performance or efficacy of the drug product. XRPD can be used to measure some of the Critical Material Attributes (CMAs) needed to demonstrate that the drug product meets its QTPP. The QTPP considers the route of administration, dosage form, bioavailability, etc., as it relates to quality, safety and efficacy.

The latest XRPD solid form analysis techniques provide valuable evidence for Critical Quality Attribute (CQA) definition in support of the QTPP, by enabling researchers to:

  • Select more soluble forms of an API
  • Choose stable forms with enhanced manufacturability and storage profiles
  • Identify and exclude polymorphs that may compromise a drug’s efficacy or safety
  • Investigate solid form alternatives (polymorphs, salts, co-crystals, etc.)
  • Ensure that all relevant polymorphs are identified and described in related patents

Gathering such physicochemical data is vital at multiple steps of the drug development process. Solubility and stability of the drug substance must be maintained as the API moves from the early development phase into the clinic and towards the goal of approval, and XRPD is a helpful technique to monitor this.

XRPD is a powerful tool to help establish, confirm or optimize pharmaceutical CMAs. Its ability to detect and give predictions on changes to the solubility and stability of a drug provides researchers with critical information during drug development, from concept to manufacturing. In the next blog of this series, we will discuss how understanding the presence of polymorphic forms in drug substances can protect your patients and patents.

Download the full guide here to find out more about how XRPD can help your drug development projects

 

Written by: Robert Taylor, Posted by: Malvern Panalytical (www.materials-talks.com)

ProLab

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