Drug Development Case Studies

Developing a stable lipid delivery vehicle for drug candidates

The ability to modulate drug delivery at therapeutically effective doses over a sustained period of time, in vivo, is very challenging. In the case of poorly water-soluble drugs this requires a carefully designed matrix to manage and maintain their controlled release.

Lipid cubic phase carriers offer an effective way to transport both small molecules and larger proteins through oral and parenteral routes (those outside of the digestive tract), as well as local delivery via subcutaneous and intramuscular routes. Complex interactions between the drug and the lipid matrix govern the release profile; for hydrophilic drugs, release can be very fast. The carriers can also be compromised by naturally occurring lipolytic enzymes which act to break down the lipid microstructure.

Pfizer - Visualising coating integrity for bead drug products

Drug products in the pharmaceutical industry are commonly prepared in the form of discrete multi-particulate units. Bead products are a vehicle used in the development of controlled release drugs and are prepared by coating an inert spherical core with multiple layers, including that of the active ingredient. Components in each applied layer can have a significant impact on how the drug will be released and porosity of the layers is a critical feature related to observed dissolution behaviour. However accurate and highly resolved measurement of the physical integrity of these layers is a significant challenge in the development of advanced multi-particulate dosage forms. 

Personalising alendronate therapy when treating Osteoporosis

Osteoporosis is a bone disease that affects 200 million people worldwide and contributes to 8.9 million fractures annually. The condition causes a loss of bone mass and structure which in turn leads to bones becoming weak and breaking, usually during a trip or fall. The disease is prevalent in people over 55, and in particular women, due to the loss of oestrogen hormone during the menopause. Osteoporosis is becoming increasingly prevalent in men who receive cancer therapies which supress testosterone levels. Bisphosphonates are a family of medicines which are commonly prescribed to treat osteoporosis. The most common types are alendronate and zoledronate which aim to strengthen osteoporotic bones by slowing down the activity of bone cells.

Setting the foundation for new anti-malaria drugs

Malaria is one of the most prevalent parasitic diseases of humans and affects 216 million people worldwide. Many years of research have been dedicated to finding the most effective and affordable drugs to prevent infection, which have to date been very successful.  Most recently the challenge has been the growth in resistance to existing treatments, which has driven further research into a new generation of anti-malarial drugs.

Characterising variants in clinical grade biopharmaceuticals

Medicinal products extracted from biological sources, called biopharmaceuticals or biologics, must be carefully produced to ensure that only high purity active material is generated. Biopharmaceutical manufacturing processes can have an impact on the amount of product-related variants in the final clinical material. Understanding and controlling amounts of these product-related variants is a major challenge in the development of biopharmaceutical products.

Drug characterisation with GSK

Drug products are manufactured to an extremely high standard to maintain product safety when taken by patients. Specifications used throughout the manufacturing process cover not only the drug itself, but also the level of potential impurities (chemical, solvent, or polymorph), which are set to limits that are monitored by regulatory bodies to uphold safety and product quality requirements. X-ray powder diffraction is a key analytical technique in the pharmaceutical industry for characterising drug compounds. This is used for throughout the development process to fingerprint compounds and quantify impurities.

Polymorphism in painkillers: a crystallographer’s headache

Along with many pharmaceutical materials, sodium diclofenac, a commonly used painkiller, can crystallise in many different forms depending on the manufacturing and formulation conditions. Each crystalline form may have very different biological and physical properties including bioavailability, drug delivery mechanism and shelf-life. Full characterisation and optimisation of solid forms of an API is therefore critical.