Injectable sustained-release drug-delivery systems in clinical trials
Several clinical trials of injectable sustained-release drug delivery systems are currently conducted in the US. Some examples
of injectable sustained-release drug delivery systems currently in clinical trials are listed in Table III.
Table III. Examples of injectable sustained-release drug delivery systems in clinical trials.
Phase I pharmacokinetic-pharmacodynamic studies are ongoing for microsphere formulation of progesterone to establish the minimum
effective dose of progesterone microspheres suspension, for weekly intramuscular injection. Phase III clinical studies of
aripiprazole for once monthly IM depot administration are ongoing to evaluate efficacy, safety, and tolerability. Phase I
trials are in progress with once-monthly IM injection of octreotide pamoate to investigate safety and tolerability of an octreotide
extended long-acting formulation after a single dose in humans. Phase III studies of pasireotide long-acting release formulation
are underway to evaluate the efficacy and safety of pasireotide LAR.
SABER is a potential parenteral in situ-forming system, and this system consists of sucrose acetate isobutyrate (SAIB), a pharmaceutically acceptable solvent, and
one or more additives. One characteristic of the system is that a SAIB/solvent mixture has a low viscosity, but upon injection,
the viscosity increases substantially as the solvent diffuses away from the SAIB (63). After dissolving or dispersing the
drug in the SAIB/solvent solution, this solution is injected subcutaneously or intramuscularly. Upon injection, the solvent
dissipates from the SAIB, and the increased viscosity controls the release of the drug from the gel. SABER-bupivacaine is
designed to continuously deliver bupivacaine, a common local anesthetic, up to 72 hours to treat local post-surgical pain.
This system injected at the surgical site prior to the wound closure and is currently in Phase III clinical studies in the
ReGel (BTG, London) is a thermally reversible gelling system and is based on biodegradable triblock copolymer composed of
PLGA–PEG–PLGA. Immediately upon injection and in response to body temperature, an insoluble gel depot is formed. OncoGel (BTG)
is supplied as a frozen formulation of paclitaxel in ReGel and is entering Phase II trials. OncoGel is being injected directly
into the tumor for oesophageal tumors, and the gel disappears in four to six weeks as it releases the paclitaxel.
As evident by the growing number of sustained-release injectable pharmaceutical products on the market, injectable depot systems
are becoming one of the most effective systems for long-term drug delivery. Owing to the enhanced quality of life and cost
of therapy supported by the advances in drug formulation and polymer science, more sophisticated injectable depot systems
will be developed and commercialized in the near future. Moreover, the introduction of more potent drugs and protein/peptide
drugs are particularly good candidates for formulation as long-acting parenteral depot systems. Polymer-based injectable depot
systems for protein/peptide drugs have many advantages such as protection of sensitive proteins from degradation, prolonged
or modified release, pulsatile release patterns, and enhancement of patient compliance. These important and unique advantages
offer potential commercial success of future sustained-release injectable pharmaceutical products that have novel active pharmaceutical
ingredients, including therapeutic proteins and peptides.
Yun-Seok Rhee is research associate professor at Sungkyunkwan University, School of Pharmacy, Suwon, Gyeonggi-do, Republic of Korea. Chun-Woong Park is a postdoctoral fellow and visiting scholar, Patrick P. DeLuca is an emeritus professor, and Heidi M. Mansour* is an assistant professor of pharmaceutics and pharmaceutical technology, all at the University of Kentucky College of Pharmacy,
Department of Pharmaceutical Sciences–Drug Development Division, 789 S. Limestone St., Lexington, KY 40536-0596, tel. 859.257.1571,
. Heidi M. Mansour is also a member of Pharmaceutical Technology’s edtorial advisory board.
*To whom all correspondence should be addressed.