eBook: How a CDMO Can Help Overcome LNP & Liposome Challenges - 14

Table 1. LNP formulations containing carvedilol and
SEM images of particulates.
as
sustained
release,
stabilized injectable
lipid
nanoparticle formulations with three different drug
loading and particle sizes as shown in Table 1.
Dissolution profile (Figure 4A) shows an extended
release over 24 hours for all three formulations. The
in vivo PK data from two formulations show these
lipid nanoparticles when administered IV in two
groups of rats delivered drug over an extended period
(>24 hours) compared to drug in solution (Figure
4B). Taken collectively, these data further suggest
the lipid compositions play an important role in controlling
the release of drugs over extended periods.21
Summary
The decision for selecting the right and most suited
technology for formulating a complex molecule
could be challenging as it depends on the physico-chemical
properties of an API. In instances where
the API is thermally labile and poorly soluble, the
choices are limited for ASDs like hot melt extrusion
(HME), Kinetisol®, or even spray drying (SD) unless
carried out under controlled temperature. In such
cases, the lipid-based technologies might be more
relevant, wherein, the decisions can be made swiftly
and tailored to meet the specific formulation needs
Figures 4A & 4B. Dissolution (A) and PK profile in rat (B) of carvedilol in
liposomal preparations composed of phospholipids.
with regard to excipients' suitability and compatibility
with the API. Long-term stability and minimizing
API degradation and impurities could be of
relevance when selecting SLN vs NLC formulations
for oral and injectable formulations. To expedite further,
computer-based simulation models are used to
predict stability and degradation of APIs and help
select the appropriate excipients to design better
and smarter formulations to select and streamline
the process and expedite the development. Lipidbased
excipients for parenteral formulations, requiring
phospholipids and long-circulating phospholipids
and sterols for liposome stability, further help
in creating the most stable API environment within
encapsulated lipid nanoparticles from the formulation
toolkit of the decision tree as shown in Figure
5. Thus, an understanding of an API's characteristics
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