Successful Formulation Case Study

Aug 20, 2019

Successfully Formulating A Poorly Soluble And Highly Variable API

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The Challenge
A mid-size pharma company has been working with TEDOR to manufacture a highly
complicated product with a large market value.

TEDOR was asked to devise a formulation which accommodates a difficult API that is
poorly soluble and features highly variable bioavailability.

The in vivo variability was a major challenge for the product as not only could each
patient react differently to the tablet, but the same patient could also react differently
if taking the tablet at different times of day or on alternate days.

An initial formulation was developed with a desired dissolution profile and dosed as
a three-way replicate in fasting and fed conditions. This pilot biostudy failed in most
of the categories, so TEDOR helped the customer embark on a fact-finding mission
to discover why, and to ensure that the reformulation’s physical behavior (time to
disintegrate, disintegration pattern etc.) is as desired while maintaining the desired
dissolution profile.

The Solution
TEDOR conducted experiments to obtain the desired physical behavior of the
formulation. Our team knew we needed to find a dissolution medium that ensures the
new product’s dissolution predicts formulation behavior in vivo. However, because the
product is pH-dependent water soluble, there were not many media sources available.

TEDOR had to think outside of the box and use the physical behavior of the formulation
to our advantage. We reformulated the product utilizing an unconventional granulation
method that used a lubricant during the wet granulation stage. This unusual method
helped match the DT/physical behavior and achieved desired dissolution profile.

The Outcome
The manufacturing process developed by TEDOR was successful in producing a
consistently uniform product which was dosed as a fully replicate design for both
fasting and fed condition and behaved as expected in vivo.

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