from lab to patient: optimising oncology formulations with purified excipients

In 2024, we hosted a live webinar exploring the impact of our Super Refined™ excipients on various chemotherapeutic formulations. This blog will explore some of the key learnings from the webinar. 

Oncology continues to account for the largest share of the global pharma development pipeline, with 19.3 million new cancer diagnoses annually. Cancer is a result of uncontrolled proliferation of cancerous cells that cannot be halted by normal immune function, therefore introducing the need for therapeutic intervention. However, cancer cells often develop chemotherapeutic resistance due to their constant genetic mutations, rendering treatments less effective over time, and requiring the need for continuous development of new drugs and combination therapies to overcome this resistance. Lack of specificity in traditional chemotherapy causes damage to healthy cells, not just cancerous ones, which stops us from being able to treat cancer more aggressively or effectively. 

Solubility and stability issues, especially common in small molecule oncology drugs, can cause the drug to fall outside the target profile in terms of shelf-life, bioavailability, efficacy and sometimes even safety. Solubility challenges are becoming even more common today with modern small molecule drugs being more complex or hydrophobic, which gives them better permeation into cell membranes, but can complicate the drug’s aqueous solubility. Solubility and stability issues can result in regulatory challenges, delayed drug approval and reduced speed to market, posing a risk not only to drug developers, but to patients by delaying them a treatment they might need.   

We at Croda recognise this need for excipients that can improve solubility and stability, allowing you to create ultra-stable formulations to avoid API degradation, extending your drug shelf-life to the desired target profile. We understand each of these challenges as your formulation partner, and while we cannot solve everything, we can help you tackle these very common solubility and stability issues. 

Our platforms offer solutions to meet each of your needs in oncology drug development - our high purity ingredients can be used for all classes of cancer drugs ranging from low to very high molecular complexity, for both the bioprocessing and formulation of your drug. 

Small molecule drugs have long been the backbone of cancer treatment, directly targeting rapidly dividing cells. Microtubule inhibitors, topoisomerase inhibitors and anti-oestrogens can be formulated with our Super Refined™. During the webinar, James Humphrey, Research and Technology Specialist presented application data to support the use of our excipients to improve API stability in anti-cancer formulations. Data showed that when using standard grade excipients, after days, weeks and months there was an increase in API related impurities due to degradation. Whereas, when Paclitaxel was dissolved in Super Refined™ P35 Castor Oil, the Paclitaxel was stable across the 21-week study and has a final recovery of 95% vs 83% recovery for the standard compendial grade. Similar observations were seen with Docetaxel, a chemotherapeutic drug used in the treatment of breast, lung, prostate, gastric, head and neck and other types of cancer. Docetaxel was dissolved in Super Refined™ and standard compendial grade polysorbate 80 and PEG 400. The formulations were then aged for 12 weeks at 40°C for 12 weeks and analysed by HPLC at weeks 0, 4, 8 and 12. After 12 weeks of accelerated aging the Super Refined™ Polysorbate 80 and PEG 400 had over 90% drug recovery. Standard grades of polysorbate and PEG 400 demonstrated significant loss of docetaxel. Supporting graphs were also shown during this section of the webinar. 

Following the data insights, James then compared the main differences in impurity levels between compendial, HP and Super Refined™ Polysorbates. The latter have the highest degree of purity in terms of colour, water content, catalyst residues, peroxide and formaldehyde levels as impurities are removed in the Super Refined™ grades. Moreover, these levels of purity are maintained by packaging the Super Refined™ products under nitrogen. 

There was also a preview of our offerings for large molecule therapy development for oncology, such as mAbs and nucleic acid-based cancer therapies, from upstream to downstream biomanufacturing. This included our innovative replacement to the banned chemistry Triton™ X-100 – Virodex™. Virodex™ TXR-1 and TXR-2 exhibit equivalent or superior performance to Triton™ X-100 in all of the head-to-head comparisons including the potency and kinetics of virus inactivation as well as cell lysis and protein compatibility, ensuring the safety of biologics for oncology.  

We would recommend this webinar to professionals across all stages of oncology drug development: formulation scientists, research scientists, drug product developers and pharmaceutical engineers.

Watch on demand today!