Overcoming Formulation Difficulties

How does the pharmaceutical world meet thedrug, solvents must be used — thus increasing
challenge of the ever-increasing pace inthe cost and difficulty of the process.
pharmaceutical product development? OnePharmaceutical formulators have developed direct
shortcut solution for formulators is to usecompression manufacturing processes for these
high-performing excipients.drugs through the use of Starch 1500. Content
The changing landscape of the pharmaceuticaluniformity is achieved by first preparing a
industry is increasing the commercial pressure onpre-blend of the API and Starch 1500, followed by
R&D groups to shorten time to market for newthe addition of the remaining ingredients and
products. As a result, formulators are demandingtabletting. The granular morphology of this unique
more functionality and performance from theirexcipient combined with its inherent moisture
pharmaceutical excipients. These ingredients nowcontent produces an ordered mix through
play a critical role in achieving stability, reducingadhesion and hydrogen bonding.
costs and improving manufacturing efficiencies.Humidity control
They must also produce a robust dosage formMoisture-sensitive drugs present another challenge
that is unaffected by variations in processto formulators. Potential problems associated with
parameters or other ingredients.these APIs include reduced flow properties, as
Faced with shorter development cycles and morewell as changes in dissolution rates, chemical
complex active pharmaceutical ingredients (APIs),stability and physical stability (in terms of color, for
formulators cannot afford the luxury ofexample). Some ways to protect moisture
investigating new excipients. They need to usesensitive products involve humidity-controlled
proven ingredients in the development of newmanufacturing conditions, protective packaging,
tablets or capsules, and rely heavily on themoisture barrier film coating and, most
producers of these ingredients to identify newimportantly, selecting excipients that minimize
applications.moisture sensitivity. In this selection process, it is
Enhancing drug formulationimportant to understand the difference between
Multi-functional excipient products have beenmoisture content and water activity.
shown to offer unique synergies with manyTotal moisture content is, typically, measured by
common ingredients. For example, combiningloss on drying. However, this method does not
Starch 1500 – a partially pregelatinized maizedistinguish between bound moisture (unavailable
starch from Colorcon® – withfor chemical interactions) and unbound moisture
microcrystalline cellulose results in very(available for chemical interactions). A better
compactable formulations with excellent dissolution.measure is water activity or equilibrium relative
This minimizes the need for super-disintegrantshumidity, which shows only the unbound water
that can affect stability. The flow properties andthat is free to interact with the drug.
friability of lactose blends can also be greatlyFor example, although the moisture content of
improved. Moreover, incorporating speciallyStarch 1500 is higher than some other excipients',
designed pregelatinized starch products canthe water content is considerably lower.
reduce the amount of lubricants, which are knownTherefore, it will equilibrate slower when exposed
to cause over-blending problems, and affectto moisture conditions and may, preferentially,
dissolution and film coating quality.bind the moisture, preventing interaction with the
As APIs become more sophisticated, many ofdrug. Starch 1500 has been used to develop
them are effective at low-dose concentrationsformulations with proven stability for many
and are often micronized. But low-dose medicinesmoisture-sensitive APIs, including aspirin and
can be a challenge to formulate due to problemsranitidine. These robust formulations have helped
with content uniformity and physical stability.lower costs by reducing the need for special
Traditionally, these drugs have been manufacturedmanufacturing conditions and expensive packaging.
through wet granulation to assure that each tabletAs formulators turn to proven excipients to meet
contains the proper amount of active material.today's challenges, multi-functional excipients such
This process can, however, be costly andas Starch 1500 offer a long history of reliability
time-consuming because of the many stepsand efficacy, and continue to provide benefits in
involved. If water has a detrimental effect on thethe development of new applications.