S U B CUTANEOUS
DELIVERY
Subcutaneous Delivery of Small Molecule
Formulations: An Insight Into Biopharmaceutics &
Formulation Strategies
By: Viral Kansara, PhD; Amitava Mitra, PhD; and Yunhui Wu, PhD
ABSTRACT
Subcutaneous (SC) drug delivery systems are becoming increasingly important injectable techniques to
administer a wide range of therapeutic formulations. This review provides an insight into biopharmaceutical and
formulation aspects of systemic delivery of small molecules upon SC administrations. The review also provides an
overview of the factors that govern SC absorption and describes research and technologies focused on utilizing or
modifying SC absorption mechanisms. General guidance on conducting pharmacokinetics and tolerability studies has
been briefly covered. Various SC formulation strategies and marketed and in-pipeline SC formulations for delivering
small molecules have been thoroughly reviewed. It was summarized that even though SC administration continues to
be the main route for the delivery of protein and polypeptide formulations, successful application of SC formulations
for the delivery of small molecules with poor aqueous solubility is somewhat limited. Integration of various
biopharmaceutical and formulation factors into the overall SC formulation strategies should be carefully considered
in designing safe and effective SC drug delivery systems.
INTRODUCTION
OPPORTUNITIES &
LIMITATIONS
SC injections are usually administered
in small volumes (0.5 to 1 mL; upto 2 mL)
into the outer surface of the upper arm,
anterior surface of the thigh, abdomen, or
buttock, and can be self-administered. As
shown in Figure 1, during SC
administration, a needle is inserted through
the epidermal and dermal layers of the skin
and into the fatty subcutaneous tissue.1
Following SC administration, drug
molecules enter the systemic circulation by
direct absorption into SC blood capillaries
or indirectly via absorption into the
lymphatic capillaries, which are present
within the interstitial space. Therefore,
characterization of the SC absorption
process is crucial to the design of improved
SC drug delivery systems and the
interpretation and development of useful
pharmacokinetic-pharmacodynamic
relationships.
SC injections have several immediate
advantages over intramuscular (IM) or
intravenous (IV) administrations. In
contrast to the skilled personnel required
for the administration of IV and IM
injections, SC injections can be
administered by the patient. 2 Slower
absorption of subcutaneously
administered drug, as compare to IV
administration, may avoid the risks of
bolus administration. A small needle is
required (length of ⅜ to ⅝ of an inch),
and the injections are not generally
painful and carry a reduced risk of
infection and other complications. For
infectious agent delivery, SC injection
may prove beneficial by restricting the
infection to local site of injection. For
patients requiring multiple doses, SC
injections offer a broader range of
alternative sites. 3
From many perspectives, including
reduced pain, improved patient quality of
life, reduced cost of patient care, and
reduced risk of infection, SC represents a
FIGURE 1
Comparative sites of injection for subcutaneous,
intramuscular, and transdermal administration.
( http://publications.nigms.nih.gov/medbydesign/
chapter1.html)
