Solving Solubility in Oral Cancer Treatment


Oral anticancer medications are preferred by patients, and allow continuous treatment.1,2.

However, the difficulty of formulating oral drugs can limit their viability. For example, the vast majority (≈90%) of oral drugs in development have poor aqueous solubility.1

Solubility—a drug’s ability to dissolve in the gastrointestinal fluid—is one element essential to consistently achieving optimal efficacy and safety.1

of oral drugs in development have low solubility

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of available oral anticancer drugs may be compromised by poor solubility


With anticancer drugs—which may have a steep dose-response curve and a narrow therapeutic index—the solubility problem is particularly serious.1,3 In nearly 50% of approved oral anticancer agents, dissolution-limited absorption may

  • Compromise bioavailability1
  • Increase variability in blood concentrations, which may lead to risk of1
    • Subtherapeutic exposure and lack of response
    • Excessive exposure and toxicity
    • Changes to systemic exposure when administered with food

For example, many tyrosine kinase inhibitors have poor solubility, with drug exposure that varies from patient to patient.3 Hormonal agents such as bicalutamide and exemestane are also poorly soluble, with high variability.1

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Methods of improving solubility in orally-administered drugs include4

  • Lipid-based systems
  • Solid dispersion matrices
  • Use of surfactants

While these formulations can be effective, they may be difficult to stabilize.4,5

Another strategy is particle size reduction to increase the rate of dissolution.6


Lipid-based Systems

Amorphous Solid Dispersions

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As particle size decreases, surface area increases proportionately.7 For example, a 10-fold decrease in particle size would lead to a 10-fold increase in the overall surface area of the drug, allowing more interaction with gastrointestinal fluids—and greater dissolution before passing through sites of absorption in the digestive tract.8 The dissolution rate increases in direct proportion to increased surface area.6

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The SoluMatrix Fine Particle Technology™* is a proprietary manufacturing process that may unlock the potential of certain oral drugs by changing how well they dissolve and how efficiently they are absorbed.9

A patented dry-milling process grinds organic/ pharmaceutical active compounds into a fine powder, reducing the particle size of poorly soluble drugs to the submicron level—10 to 200 times smaller than conventional drug particles. At the same time, a custom blend of excipients both aids in the grinding process and protects the active particles from subsequent agglomeration.9

*Licensed to Churchill Pharmaceuticals LLC from iCeutica, Inc.


In the human body, drug absorption takes place primarily in the small intestine and specifically in the duodenum—where faster dissolution can lead to enhanced bioavailability.10-12

Since the window of duodenal transit is typically less than 5 minutes, conventionally produced oral drugs with larger particles may not dissolve in time for optimal absorption in this key area.7,10

The submicron-sized particles produced by the SoluMatrix Fine Particle Technology™ dissolve more rapidly, allowing more drug to be absorbed in the duodenum and requiring less drug per dose.6,9

With conventional particles, a larger drug load may be needed to produce clinical effect, which can lead to GI toxicity and associated compliance issues.6

While the enhanced absorption of the SoluMatrix Fine Particle Technology™ allows greater bioavailability and may promote more consistent blood levels of the active agent—both within individual patients...9

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...and among the overall treatment population.13,14

  • Higher steady-state trough concentrations may reduce the risk of suboptimal exposure and treatment failure
  • Lower peak concentrations may reduce the risk of toxicity
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These quality-driven improvements can result in greater therapeutic potential9

  • Efficacy
  • Safety
  • Efficiency

The Churchill promise of optimized products, responsibly delivered, leverages the use of the SoluMatrix Fine Particle Technology™

And reflects our ongoing commitment to excellence in the development of pharmaceutical products.

1. Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. 2016;50:247-263.

2. Banna GL, Collovà E, Gebbia V, et al. Anticancer oral therapy: emerging related issues. Cancer Treat Rev. 2010;36(8):595-605.

3. Herbrink M, Nuijen B, Schellens JHM, Beijnen JH. Variability in bioavailability of small molecular tyrosine kinase inhibitors. Cancer Treat Rev. 2015;41(5):412-422.

4. Gupta S, Kesarla R, Omri A. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems. ISRN Pharm. 2013;2013:848043.

5. Kalepu S, Manthina M, Padavala V. Oral lipid-based drug delivery systems – an overview. Acta Pharmaceutica Sinica B. 2013;3(6):361-372.

6. Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm. 2011;420(1):1-10.

7. El-Kattan A, Varma M. Oral absorption, intestinal metabolism and human oral bioavailability. In: Paxton J, ed. Topics on Drug Metabolism. Rijeka, Croatia: InTech; 2012:1-34.

8. Williams HD, Trevaskis NL, Charman SA, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315-499.

9. Nanoformulation Utilizing SoluMatrix™ Technology, Poster and Abstract Presented at the 40th Annual Meeting & Exposition of the Control Release Society (CRS), Honolulu, HI; July 21-24, 2013

10. Wilson CG. The organization of the gut and the oral absorption of drugs: anatomical, biological and physiological considerations in oral formulation development. In: Wilson CG, Crowley PJ, eds. Controlled Release in Oral Drug Delivery. New York, NY: Springer US; 2011:27-48.

11. Pang KS. Modeling of intestinal drug absorption: roles of transporters and metabolic enzymes (for the Gillette Review Series). Drug Metab Dispos. 2003;31(12):1507-1519.

12. Sutton SC. Understanding the gastrointestinal, drug and dosage form processes controlling absorption: I. GI physiology. American Association of Pharmaceutical Scientists. Webinar presented: July 25, 2013. Accessed February 21, 2017.

13. Data on file, Churchill Pharmaceuticals, LLC. 15. Undevia SD, Gomez-Abuin G, Ratain MJ. Pharmacokinetic variability of anticancer agents. Nat Rev Cancer. 2005;5(6):447-458.

14. Undevia SD, Gomez-Abuin G, Ratain MJ. Pharmacokinetic variability of anticancer agents. Nat Rev Cancer. 2005;5(6):447-458.