Route of Administration (RoA)
For pharmaceutical products, the preferred RoA is generally through oral
administration (non-parental) due to increased safety, good patient
compliance, ease of ingestion and cost-effectiveness. However, the
pitfall of macromolecular biopharmaceuticals is their limited
bioavailability of only 1-2% by oral administration due to limited
penetration across the intestinal epithelium, and increased
susceptibility to enzymatic degradation in the intestinal lumen (Ovacik
& Lin, 2018; Zhao, Ji, Li, Roy, & Sahajwalla, 2013). In recent years,
therapeutic antibodies with diverse RoA have been approved for treatment
of diseases. The most common RoA for mAbs are intravenous (IV),
intramuscular (IM), or subcutaneous (SC) administrations, with
injections being the principal source of delivery (Table 1) (Zurdo,
2013). Other administration methods, e.g. ocular delivery, also exist
for site-specific drug administration and lowering of side effects by
localized therapy (Homayun, Lin, & Choi, 2019; Mandal et al., 2018).
When compared to SC or IV, IM administration is not the ideal route of
administration for mAbs due to low bioavailability (Homayun et al.,
2019). IV administration is generally used for mAbs, whereas IM
injections are most commonly used for vaccines (Mitragotri et al.,
2014). Compared to other parental RoAs, SC injections are the most
convenient as they facilitate patient self-administration and are the
least invasive (Mitragotri et al., 2014; Zurdo, 2013). Despite that
however, SC formulations place considerable constrains in terms of
stability, aggregation and viscosity due to the need of high
concentrated doses in low injection volumes (Viola et al., 2018; Zurdo,
2013).
Table 1 : Characteristics of different route of administration
(RoA) for monoclonal antibodies. Data gathered from Ortega et al.
(2014), Ryman & Meibohm (2017) and Zhao et al. (2013).