Chemistry Reference
In-Depth Information
anionic and cationic surfactants (model systems investigated were SDS and
n
-dodecyltri-
methylammonium chloride, respectively). Anionic surfactants tend to be attracted to the
positively charged ether linkages in PEGs or PPGs, as the lone electron pair on the ether
oxygen tends to leave a slightly positive tendency. This promotes complexation of the
surfactant head groups and adsorption of the hydrophobic tail to the carbon-containing region
of the polymer chains. In contrast, cationic surfactants tend to repel from the polyglycols due
to repulsion from the ether oxygen, hence showing weak associations in aqueous solution.
The effects of pH on associations for anionic surfactants are greater due to their electrostatic
attractions; however, they are less signi
cant for cationic surfactants where their associations
are poor with polyglycols. Especially with pharmaceutical formulations where pH effects are
significant throughout the GI tract, these considerations must be made when choosing a
polymer
surfactant system in conjunction with the drug molecule.
Efforts to improve the bioavailability of some naturally derived compounds have
been studied using PEG
-
surfactant-based systems. In an example by Hu et al., ASDs
were designed for daidzein, a cardiovascular drug extracted from Chinese herbal
medicine [57]. The components studied were PEG 10,000 and Tween 80, coprocessed
with the drug to make a solid dispersion solidi
-
ed from ethanol. PEG alone at high PEG
to drug ratios (8:1) had good solubilizing power for daidzein. The addition of Tween 80
slightly improved the solubility of the drug at lower PEG:drug ratios (2:1 and 5:1);
however, it seemed to have a negative effect at 8:1. The authors eluded that the solidity of
the matrix and processing of the dispersion may be factors that affect the ternary
interactions. Another naturally derived compound studied was oleanolic acid (OA), a
triterpenoid compound that exists widely in natural plants, for anti-in
ammatory and
other protective functions [58]. In this case, polysorbate 80 was found to increase the
solubilization and release pro
le for OA when it was formulated in a PVP K30 solid
dispersion matrix. The solid dispersion provided dissolution enhancement of up to
twofold over the simple physical mixture of components.
A PEG-incorporated amphiphilic graft copolymer that consists of polyvinylcapro-
lactam
polyethylene glycol, with a trade name of Soluplus
, has also
been used in many ASD applications [59]. This polymer may have both solubilizing and
delaying of precipitation characteristics to enable better drug absorption. Three drugs,
danazol, itraconazole, and fenofibrate, were studied using this polymer to make solid
solutions by hot melt extrusion (HME) techniques. These drugs are known to have food
effects, typical of many BCS class II, low-solubility/high-permeability compounds. The
absorption studies in dogs showed signi
-
polyvinyl acetate
-
cant increases in bioavailability over the
crystalline drug and fairly good agreement between the
in vitro
dissolution studies.
Due to the improvement in bioavailability, food effects may be less likely with these
formulations as solid solutions. It is possible that the graft copolymer and drugs may
form mixed micelles in the gastrointestinal tract with components such as bile salts and
phospholipids present in gastric
fluids.
In addition to PEG-based systems, PVP deriv-
atives have often been used in second-generation ASDs. However, combinations of PVP
derivatives with surface-active molecules have been bene
2.3.3.2 PVP-Based Systems
cial to many compounds. The
dissolution and precipitation behavior of itraconazole, an antifungal, was studied from a
