22 Jun Prostate Cancer: More Efficient Formulation of Zytiga Improves Absorption

MedicalResearch.com Interview with:

Dr. Schultz

Dr Hayley Schultz | Research Associate BPharmSci(Hons), PhD
UniSA Clinical and Health Sciences
University of South Australia
Adelaide SA  

MedicalResearch.com: What is the background for this study?

Response: Zytiga is a blockbuster medication for treating prostate cancer containing the active ingredient abiraterone acetate, however the formulation is incredibly inefficient. Patients must take 1000 mg per day and fast for 2 hours prior to and 1 hour following its administration. This is because the drug is very water insoluble and has an oral bioavailability of less than 10%. This means only up to 10% of the dose is absorbed from the intestine and enters systemic circulation where it can have a therapeutic effect. The rest of the drug, at least 90% of the dose, moves through the gastrointestinal tract undissolved and is wasted down the toilet. Patients are required to fast when taking the medication as the drugs absorption is heavily and unpredictable increased in the presence of fatty and oily food.

We developed a more efficient oral formulation for abiraterone acetate with a greater oral bioavailability, to reduce the dose of the drug and its side effects.

MedicalResearch.com:? What are the main findings? How does the new formulation differ from Zytiga?

Response: We developed a lipid (oil) based oral formulation for abiraterone acetate to mimic the increased absorption observed when in the presence of oily food. The formulation consisted of abiraterone acetate pre-dissolved within an oil at very high levels and encapsulated within porous silica micro particles to form a power that could be made into tablets or filled into capsules.

We observed improved solubilisation of the drug from our formulations under simulated gastrointestinal conditions, and also no change in solubilisation due to the presence of food. In a pre-clinical trial, our formulation displayed a 40% improvement in oral bioavailability, compared to Zytiga. The new formulation, contains pre-dissolved abiraterone acetate, so it can be quickly and efficiently absorbed, whereas Zytiga contains crystalline abiraterone acetate, so it slowly and partially dissolves with limited absorption.

MedicalResearch.com: What should readers take away from your report?

Response: The take away message for readers is that a lipid based formulation strategy can significantly improve the oral absorption of abiraterone acetate. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Research should focus on the further development of various lipid based formulation for abiraterone acetate. Specifically, we require formulations with high drug loading, improved oral absorption and the ability to mitigate the pharmaceutical food effect. This would reduce the dose for patients and allow them to take the medication independent of food.

MedicalResearch.com: Is there anything else you would like to add?

Response: This research was undertaken by Dr Hayley Schultz during her PhD under the supervision of Prof Clive Prestidge at the University of South Australia Cancer Research Institute. Part of this research was funded by the Gould Experimental Science Grant.

This research is linked the the following peer reviewed articles:

• Schultz, H.B., Joyce, P., Thomas, N. & Prestidge, C.A. (2020). Supersaturated-Silica Lipid Hybrids Improve in Vitro Solubilization of Abiraterone Acetate. Pharmaceutical Research 37, 77. https://doi.org/10.1007/s11095-020-02795-y
• Schultz, H. B., Wignall, A. D., Thomas, N., & Prestidge, C. A. (2020). Enhancement of abiraterone acetate oral bioavailability by supersaturated-silica lipid hybrids. International Journal of Pharmaceutics, 119264. https://doi.org/10.1016/j.ijpharm.2020.119264 

Citation:

Schultz HB, Wignall AD, Thomas N, Prestidge CA. Enhancement of abiraterone acetate oral bioavailability by supersaturated-silica lipid hybrids. International Journal of Pharmaceutics. 2020 May;582:119264. DOI: 10.1016/j.ijpharm.2020.119264.https://www.sciencedirect.com/science/article/pii/S0378517320302489

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Last Updated on June 22, 2020 by Marie Benz MD FAAD