Want to know more?

___________________________________

Industrial Liaison Group:

Tel: +44 (0) 1235 778797

Day 15 - Drug Development at Diamond

We are only 10 days away from the big day!! It's day 15 of the Diamond Industrial Liaison advent calendar. Now you know all about the research techniques that are on offer here at Diamond, let's show you how they can be used by researchers in both industry and academia; starting with an introduction to the development of drugs for the pharmaceutical industry.

Designing a potent and selective drug is only part of the story of creating a new medicine. Delivering that drug safely to the correct part of the body at the right concentration, at the optimum rate is a considerable challenge and it is here that the formulation of the drug is crucial. In addition, formulations must be stable under transport and storage conditions for an acceptable period of time and remain safe and effective as a treatment. With ever increasing scrutiny, it is the responsibility of the company seeking to market a drug to test it and submit evidence to the regulatory bodies that the product is not only effective, but also safe for patients.

Structure

Pharmaceutical active ingredients (APIs) can exist in a variety of distinct solid forms, including polymorphs, solvates, hydrates, salts, co-crystals and amorphous solids. Polymorphs are crystalline materials that have the same chemical composition but different molecular packing. This concept is well demonstrated by the different crystalline forms of carbon. Diamond, graphite, and fullerenes are all made of pure carbon, but their physical and chemical properties vary drastically.

Polymorphs are one type of solid form. Other solid form types include solvates (crystalline materials made of the same chemical substance, but with molecules of solvent regularly incorporated into their unique molecular packing), hydrates (where water is the solvent), and amorphous forms (where the substance has the same chemical composition, but lacks the long-range molecular order of a crystalline form of the same substance).

Many organic and inorganic compounds, including APIs, can exist in multiple solid forms. Some APIs may have only one or two known solid forms, others may exist in twenty different forms, each having different physical and chemical properties. Sometimes the properties of two solid forms of a drug are quite similar but in other cases, the physical and chemical properties can vary dramatically and have great impact on pharmacokinetics, ease of manufacturing, and dosage form stability. Properties that can differ among solid forms of a substance include colour, solubility, crystal shape, water adsorption and desorption properties, particle size, hardness, drying characteristics, flow and filterability, compressibility, and density. Different solid forms can have different melting points, spectral properties, and thermodynamic stability and in a drug substance, these variations in properties can lead to differences in dissolution rate, oral absorption, bioavailability, levels of gastric irritation, toxicology results, and clinical trial results. Ultimately both safety and efficacy are impacted by properties that vary among different solid forms.

A regulatory drug application now must contain sufficient information to show that the drug substance is the "same" as that of the reference listed drug and it is here that structural investigations, such as polymorph studies, are essential.

Formulation

Drug formulations can be composed of up to 95% of the total volume of inactive (non-drug) ingredients, known as excipients. An excipient is a natural or synthetic substance formulated alongside the active ingredient of a medication,included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients (thus often referred to as "bulking agents", "fillers", or "diluents"), or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility.

Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerned by, for example, facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors.

Pharmaceutical regulations and standards require that all ingredients in drugs, as well as their chemical decomposition products, be identified and shown to be safe.

Synchrotron techniques for drug development

So where do synchrotron research techniques fit into all of this? Depending on the nature of the problem, a wide variety of options are available here at Diamond which provide different, and very often complementary, information to gain an greater understanding of the system in question.

Popular techniques for investigating structure in pharmaceutical formulations include X-ray diffraction and crystallography that are able to provide nanoscale structural information, small angle X-ray scattering which can provide information about phase behaviour and microstructure in soft systems, typically solutions, suspensions, gels and emulsions. X-ray absorption spectroscopy is able to provide a direct probe of the chemical environment within a sample which could be a crystalline or amorphous solid, a liquid or even a gas. High resolution measurements such as powder diffraction and X-ray fluorescence also permit chemical mapping of samples. X-ray imaging and related techniques can provide direct images of samples including tomographic studies to examine complex internal structures in tablets or capsules or even imaging devices.

How can Diamond help with drug development research?

Ranging from polymorph and co-crystal studies on APIs through to imaging and diffraction on tablets to structural changes on dissolution through to spectroscopic investigation of salts and precipitates, the variety of experiments that can be accessed using synchrotrons such as Diamond to aid with pharmaceutical formulation design and development is extensive.

Some examples of how Diamond can play a part in drug development include:

Structural identification and characterisation of crystalline solids under controlled environmental conditions;
Element selective investigation of a wide range of materials; crystalline and amorphous and at very low concentrations;
Phase behaviour of self-assembled systems in excipients such surfactants, lipids and polymers;
Understanding solution microstructural changes occurring during the dissolution of lyophilised APIs;
Direct imaging of tablets to understand structural defects including cracks, pores and bubbles;
Understanding structural changes associated with the use of additives e.g. rheological modifiers;
Structural characterisation of dispersions, emulsions and partially ordered materials under controlled conditions;
Element mapping to determine chemical composition of samples with very high resolution e.g. biological fibres or wheat grains.

The Industrial Liaison Team at Diamond

Would you like to know more about the techniques available at Diamond and how you can apply them to your drug development research? Do you perhaps have a structural problem that you are unable to solve in your lab or a material you wish to find out more about? Then please get in touch with the Industrial Liaison Team at Diamond.

The Industrial Liaison team at Diamond is a group of professional, experienced scientists with a diverse range of expertise, dedicated to helping scientists and researchers from industry access the facilities at Diamond. We’re all specialists in different techniques and have a diverse range of backgrounds so we’re able to provide a multi-disciplinary approach to solving your research problems. We offer services ranging from full service; a bespoke experimental design, data collection, data analysis and reporting service through to providing facilities for you to conduct your own experiments.

We’re always happy to discuss any enquiries or talk about ways in which access to Diamond’s facilities may be beneficial to your business so please do give us a call on 01235 778797 or send us an e-mail. You can keep in touch with the latest development by following us on Twitter @DiamondILO orLinkedIn.

Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.

Diamond Light Source Ltd
Diamond House
Harwell Science & Innovation Campus
Didcot
Oxfordshire
OX11 0DE

See on Google Maps

Diamond Light Source^® and the Diamond logo are registered trademarks of Diamond Light Source Ltd

Registered in England and Wales at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom. Company number: 4375679. VAT number: 287 461 957. Economic Operators Registration and Identification (EORI) number: GB287461957003.

feedback

On this website

About Diamond

For Users

Industry

Science

Instruments

Careers

Public

Procurement

Software & Tools

Sub-navigation

In This Section

Sub Navigation

Want to know more?

Day 15 - Drug Development at Diamond

The Industrial Liaison Team at Diamond