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Te c h n o l o g y

Solving Solubility in Oral Cancer Treatment

THE IMPORTANCE OF

SOLUBILITY IN ORAL AGENTS

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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 THE CHALLENGE OF ORAL

CANCER TREATMENTS

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
of available oral

anticancer drugs

For example, many tyrosine kinase inhibitors

may be
have poor solubility, with drug exposure that
compromised by varies from patient to patient. 3 Hormonal
poor solubility
agents such as bicalutamide and exemestane
are also poorly soluble, with high variability. 1

CURRENT STRATEGIES

Methods of improving solubility While these formulations can

in orally-administered drugs be effective, they may be
include 4 difficult to stabilize. 4,5

Another strategy is particle size

Lipid-based systems reduction to increase the rate
of dissolution. 6
Solid dispersion matrices
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 Use of surfactants

Surfactants Lipid-based Amorphous Solid

Systems Dispersions

As particle size decreases, surface area increases

7
proportionately. 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

8
absorption in the digestive tract. The dissolution

rate increases in direct proportion to increased

6
surface area.

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 I N T R O D U C I N G T H E S O L U M AT R I X ™ T E C H N O L O G Y

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
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*Licensed to Churchill Pharmaceuticals
LLC from iCeutica, Inc.

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 Efficacy Safety Efficiency

And reflects our ongoing commitment to excellence in the development of

pharmaceutical products.

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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.

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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.

http://www.aaps.org/uploadedfiles/content/sections_and_groups/focus_groups/in_vitro_release_and_dissolution_testing/resources/ivrdtfgsutton2013.pdf
(http://www.aaps.org/uploadedfiles/content/sections_and_groups/focus_groups/in_vitro_release_and_dissolution_testing/resources/ivrdtfgsutton2013.pdf). 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.

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