Ongoing developments
Biologic manufacturers are not really reluctant to use excipients; instead, they are more wary about selecting the right partner
with whom to develop the most efficient formulation with reduced frequency administration.
The ideal biomolecule delivery system should improve upon the conventional dosage form. Because of the large sizes of the
biomolecules under development, the invasive routes of administration, such as systemic or subcutaneous injections, will remain
the most efficient ones. We do, however, believe there is a greater role to be played by very inert excipients acting as simple
bulk carriers, such carbohydrates and polyols. Mannitol is well known for its cryoprotective properties and is used for protein's
lyophilisation. In fact, one very recent patent emphasises the use of polyols as stabilising factors for highly concentrated
antibody liquid formulations for subcutaneous administration.4 This interest in polyols is a result of their ability to prevent aggregation of proteins in solution and to provide a viscosity
compatible with subcutaneous administration.
We also advise using the latest advances in sustained release excipients to modulate the release of the biomolecule. As mentioned
earlier, polymer matrix-based sustained release formulations are of interest for injectable protein lifecycle improvement.
One particular trend in the field of particle engineering technologies is in the development of solutions that would allow
biologicals to be administered in standard solid dosage forms.
Dry emulsion formulations can incorporate soluble protein and provides them protection against degradation when in contact
with biological fluids.5 This dry emulsion can be directly compressed as a tablet6 or can first be adsorbed onto a powder with high specific surface area for better compressibility.7
As discussed earlier, the key challenges for biologics delivery include stability and achieving the desired targeting once
the biomolecules are in the body. As a supplier, we think in terms of designing excipients for specific dosage forms that
can be delivered through a specific route of administration.
Most biologics are formulated for delivery via injection. This requires very strict standards for manufacturing endotoxin-free
excipients. More recently, studies have been conducted regarding the development of non invasive oral delivery systems for
peptides using lipids and film coating technologies for better protection and more precise targeting.1,2,5,6
Overall, we believe that it is important to continue developing innovative excipient technologies that prolong the lifecycle
of biologics inside the body and, consequently, improve their delivery.
References
1. L.R. Brown, Expert Opin. Drug Deliv. 2(1) 2005.
2. M.A. Karsdal, et al., Clin. Pharmacol., 50(7) 2010.
3. B. Yu, et al. The AAPS Journal,
11(1) (2009).
4. Stable high protein concentration formulations of human anti TNF alpha antibodies. Patent US2010278822A1.
5. J. Shaji and V. Patole. Indian J Pharm Sci.,
70(3) 2008.
6. E. Toorisaka, et al., J. Control. Release,
107(1) 2005.
7. R.P. Dixit and M.S. Nagarsenken, Pharm. Dev. Technol., 12(5) 2007.
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