Application of solid dispersion systems in oral cancer drugs development

The majority of anticancer pharmaceuticals exhibit poor solubility in aqueous solutions, which can result in incomplete absorption and reduced bioavailability. Solid dispersion (SD) represents an efficacious methodology for enhancing the solubility and bioavailability of anticancer drugs. A significant number of active ingredients have been subjected to extensive research, patented, and subsequently launched on the market. Typical are Vemurafenib, Regorafenib and Everolimus….

Cancer is the leading cause of death worldwide, and chemotherapy is a highly effective treatment for cancer that can be used to target cells throughout the body, including those that are not visible after surgery.

Intravenous (IV) administration of chemotherapy agents (cancer drugs) is the optimal route of administration, ensuring bioavailability. However, there are several disadvantages, including the need for hospitalization, potential side effects, and reduced quality of life.

Oral drug delivery is now the preferred method of administration due to its convenience, lack of pain, safety, and ease of storage and transport. The primary challenge in developing oral anti-cancer drugs is ensuring optimal absorption. To achieve this, the drug must first dissolve and penetrate biological membranes, allowing it to be absorbed from the gastrointestinal tract and enter the circulatory system.

However, the majority of anti-cancer drugs exhibit poor solubility in water, which results in incomplete absorption and low bioavailability. This results in significant discrepancies in drug concentrations between individuals in clinical practice. The pharmaceutical industry is facing a significant challenge in improving the solubility of cancer drugs for oral delivery.

The use of solid dispersions to enhance solubility and bioavailability represents a promising avenue for addressing the solubility challenges associated with poorly soluble drugs.  To date, three anti-cancer drugs have been successfully researched and commercialized: Vemurafenib (Zelboraf®, Roche), Regorafenib (Stivarga®, Bayer) and Everolimus ( Afinitor®, Votubia®, Certican®, Novartis).

• Zelboraf is formulated with vemurafenib and hypromellose acetate succinate as a carrier, in a mass ratio of 30/70. The solubility of the solid dispersion containing vemurafenib was approximately 30 times greater than that of the parent compound.
• The solid dispersion of regorafenib and the PVP-25 carrier in Stivarga resulted in a 4.5-fold improvement in solubility and a 7-fold improvement in bioavailability compared to the physical blend and conventional formulation, respectively. (Patent US20230075876).
• Afinitor contains a solid dispersion of everolimus with HPMC at a mass ratio of 1:40, which has demonstrated enhanced solubility by a factor of four in comparison to the parent active ingredient.

Furthermore, research into the use of solid dispersions for cancer treatment is also being conducted on a large scale. Please find a summary of some active ingredients and carriers in the table below.

Furthermore, solid dispersions are utilized in select pharmaceutical products currently on the market, featuring active ingredients such as Nabilone (Cesamet, Novartis), Itraconazole (Sporanox, Janssen), , Rosuvastatin (Crestor, AstraZeneca)…

In conclusion, solid dispersions represent a promising avenue for enhancing the solubility and bioavailability of anticancer agents and other drug classes. It is anticipated that research and application of technology will continue to grow.

References:

1. Giới thiệu hệ phân tán rắn
2. Phân loại hệ phân tán rắn
3. Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs