Choosing the Right Capsule
Dabrafenib is a good example of
how the right capsule selection
can impact the drug application.
Dabrafenib is an oral drug for
the treatment of melanoma
with a recommended dose of
initially 150 mg twice daily and
subsequent reduction to 100 mg,
75 mg, and 50 mg twice daily.
To adequately address this
dosing requirement, two dose
strengths, 75 mg and 50 mg, have
been developed4. Dabrafenib has
an aqueous solubility of 81 μg/
ml at pH 1.2 and < 5 μg/ml from
pH 2.0 onwards.
It was found that in the
presence of the HPMC from
the capsules, which is about
20 percent of the formulation,
a supersaturated solution was
formed through its crystallization
inhibiting effect translating in
a two-fold increase of the oral
The product is marketed using
a simple formulation composed of
a diluent (MCC) and a lubricant/
glidant system (Mg-stearate,
silicon dioxide), and a two-step
manufacturing process (blending,
Modern pharmaceutical drug
development and manufacturing
increasingly demand excipients
with functional characteristics to
enhance the product performance
and increase the manufacturing
efficiency. Capsules have evolved
from the orally administered
gelatin capsule to a portfolio
of capsules with different
and application designs.
Using polymer science and
technologies, a variety of
performance characteristics can
be adapted to achieve the desired
performance of the finished
About the Authors
At Lonza Pharma & Biotech,
Sven Stegemann, Ph.D. is
Director of Pharmaceutical
Business Development; Ljiljana
Palangetic, Ph.D. and Tom
Huysmans serve as Managers
of R&D Projects; and Stef
Vanquickenborne is Senior
Director of R&D Engineering.
1 ICH, (2009, August), ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8 (R2). Retrieved from
2 Stegemann, S., et al (2007, May 21), When poor solubility becomes an issue: from early stage to proof of concept, Eur J
Pharm Sci, 31, 249 – 261.
3 Xu, S., Dai, W.G., (2013, May 2013), Drug precipitation inhibitors in supersaturable formulations Drug precipitation
inhibitors in supersaturable formulations, Int J Pharm, 453 (1), 36-43.
4 Food and Drug Administration (2014, January), TAFINLAR (dabrafenib) capsules label. Retrieved from https://www.
5 Ouellet, D., et al (2013, April 22), Effects of particle size, food, and capsule shell composition on the oral bioavailability
of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors. Int J Pharm Sci 102( 9):3100-3109.