Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 555

Table 11.4 (Continued)

Marketed Implants Characteristics Features Reference

Viadur ® —leuprolide
acetate

Osmotic implant, nonbiodegradable polymers. Delivers
a highly concentrated solution of leuprolide 400 mg/
ml continuously over 1 year at 120 g/day, for prostate
cancer. Discontinued in 2007 due to limited long-term
market viability

[209]

Vantas ® Histrelin
acetate, a
nonpeptide
analogue of
GnRH

Comprised of nonbiodegradable, crosslinked copolymer
of hydroxypropyl methacrylate and 2-hydroxyl
methacrylate. It is a 12-month subcutaneous implant

[210]

Table 11.5 Developments in the Field of In Situ Parenteral Delivery of P/P Drugs and
Their Characteristics

In Situ Implants Characteristics of These Systems Reference

Saber™ (sucrose
acetate
isobutyrate
extended-release
technology)

Sucrose acetate isobutyrate (SAIB) is a fully esterified
sucrose derivative used for sustained P/P delivery
because of its high hydrophobicity and high viscosity.
The drug is dissolved or dispersed in an SAIB/solvent
solution, and on subcutaneous or intramuscular
administration, the solvent diffuses out to leave a
viscous depot of SAIB and drug

[227,228]

Collagen minipellets
containing -
interferon

Minipellets, when administered subcutaneously in mice,
were found to release -interferon for extended periods

[229]

hGHRH or
GRF44NH 2

A biodegradable pellet system (1 mm thick by 7 mm in
diameter) made for GRF29NH 2 by compression molding
of powdered GRF29NH 2 mixed with a lactic/glycolic
acid copolymer. Releases peptide by dissolution-
diffusion from a percolating network of GRF29NH 2
particles rather than a matrix degradation release

[230]

level time profiles, and therefore reduced the application frequency [218,219] .
Various mechanisms like the use of a thermoplastic paste [220] , formation of a solid
polymer system or hydrogel by in situ crosslinking (initiated by photoinitiation, ionic
interaction) or radical-initiated polymerization [221,222] have been used to form in
situ implants. Other systems rely on water-soluble amphiphilic lipids that form vari-
ous types of lyotropic liquid crystals [223] or sugars to obtain in situ depots [224] .
MacroMed reported that both mPEG-PLGA-mPEG and PLGA-PEG-PLGA
(Regel ® ) are thermosensitive liquid drug carrier systems which can be loaded with
therapeutic agents at a temperature lower than 30°C with sol-gel transition proper-
ties at 37°C [225,226] . Table 11.5 illustrates in situ implantable products.