Chemistry Reference
In-Depth Information
R
R
O
R
O
O
O
CH
CH
2
CH
CH
2
CH
CH
2
O
O
O
n
p
COOH
COOR
COOCH
3
O
R
O
O
R
R:
CH
2
CH
OH;
CH
2
CH
CH
m >> n, p
2
3
R
Acrylates
Cellulosics
O
CH
CH
2
O
H
H
N
O
O
H
O
HO
O
n
y
n
O
Polyethylene glycol
(PEG)
Poly-(lactic-
-glycolic)
acid (PLGA)
co
Polyvinylpyrrolidone
(PVP)
Figure 6.5.
Structures of common polymers used for solid dispersions.
Typically, physical properties and structure are used to classify polymers into
different classes. Polymer properties can affect the storage conditions, shelf life,
packaging/processing considerations, dissolution, and solubility of amorphous disper-
sions. Some of the key polymer properties include size, molecular weight, types of
functional groups, ionization state, hygroscopicity, and hydrophilicity/hydrophobicity
balance. These properties, presented in Table 6.4, should be considered when selecting a
polymer to improve solubilization, dissolution rate and supersaturation. The following
are some of the key considerations:
1. Selection of a polymer with an optimum hydrophobicity for the drug substance.
For instance, hydrophobic molecules may have enhanced interactions with
polymers containing a similar hydrophobicity. The drug and polymer may
form nonspeci
c hydrophobic interactions that can hinder nucleation and crystal
growth [59].
2. Selection of a polymer with functional groups favorable for acid/base or hydrogen
bonding interactions with the drug substance. Examples include selecting PVP [66]
as a hydrogen bond acceptor for an acidic drug or HPMC-AS [65] as a hydrogen
bond donor to a basic drug. Often, crystalline lattices formby hydrogen bond donor/
acceptor interactions. By selecting a polymer with functional groups capable of
hydrogen bonding with the drug, a polymer may disrupt the crystal nucleation and/
or growth processes, thus leading to an increase in supersaturation.
3. Screening for polymers, which provide solubility enhancement or supersaturation
in relevant
in vitro
experiments [65]. Screening efforts are required in part due to the
lack of detailed physical understanding of the process of crystallization (nucleation
or growth) for a given molecule. Careful consideration of polymer properties will
help guide selection and rank order screening experiment priority.
