Biomedical Engineering Reference
In-Depth Information
small intestine, the HMPC could serve as a protection layer, which gradually dissolves
with time in the gastrointestinal tract. The time required for the HPMC coating to be com-
pletely degraded (lag time) can be controlled by the coating level. The design objective is
to make sure that the lag time coincides with the time needed to deliver the tablet to the
small intestine. It was shown that the lag time can be modulated from zero to 150 min
by HPMC coatings. The coatings that help the medicine to reach the small intestine are
collectively known as enteric coatings. Aqueous methacrylic acid copolymer dispersion
(Eudragit L 30D-55) is commonly used to form enteric coatings. The coating forms compact
structure in acidic environment, hence prevents direct contact between the ingredients
and acid, but quickly dissolves in basic condition found in the small intestine. However,
the challenge of this approach is that basic drugs could migrate into the enteric coatings
and be degraded during storage. To solve this problem, subcoating/buffer is required to
separate the drug and the enteric coating. He et al. [143] constructed multilayer structure
and made of a salt layer and an HPMC layer to be the buffer. The salt layer enhanced the
stability of the drug but had no effect on the release rate. HPMC layer controls the release
rate when the enteric layer dissolves. The overall shell life of the formulation was reported
to be 2 years. Among different commercially available HPMC, it was reported that the lag
time decreases according to Methocel K4M > E50 > E5 [144].
A recent design of biodegradable coating was reported by Murphy and coworkers [145].
Biodegradable ceramics, hydroxyapatite, was coated on a biodegradable PLGA micro-
sphere by biomimetic process. Since most protein drugs are charged, they can be bound
strongly to the mineral coating by electrostatic attraction so that proteins cannot escape
from it. It has been shown that protein release was controlled by the degradation of the
mineral coating, and burst release was not observed in their design since degradation was
a time-dependent process.
Since PLA or PLGA is biodegradable, they can be casted into films and can be coated
onto drug pellets using a hot template ((120°C, 1 h, 1 MPa) to alter release behavior. The
PLA-coated drug pellets showed a biphase release profile: a quick release due to partition
of the drug in the film during preparation and a slow linear release over days governed by
degradation [146]. Schmidmaier et al. [73] reported on poly(d,l-lactide)-coated osteosyn-
thetic implants, loaded with growth factors, and found that the incorporated growth factor
can be gradually released in a month, and the coated implant could sustain a higher load
than the bare metal implant. Degradation rate of PLA can be increased by incorporating
PEG due to decreased acidity [147]. To minimize the burst release with increased degrada-
tion rate, another coating can be applied onto the PLG-g-PEG film.
More advanced erosion-controlled designs are available. Degradable/water-soluble
coating can be applied to the amorphous solid formulation widely used in oral delivery.
The coating could stabilize the amorphous formulation and meanwhile control the rate
of dissolution of the solid formulation by its degradation/dissolution rate. Eudragit L100,
an ionic polymer, has been used in such designs [148]. The ion exchange dissolves the
Eudragit L100 coating, and the amorphous core is quickly dissolved after the coating is
gone.
The general configuration of an osmotic pressure-driven drug delivery system is a semi-
permeable coating on a drug containing core. When contacting with water, the osmotic
pressure drives water into the formulation and the pressure inside the formulation is
increased. Drug is then pushed out through orifices in the membrane due to the elevated
pressure. A lag time is usually observed, and the release of the drug is linear. The coating
can be asymmetric: the coating is composed of a semipermeable polymer with discrete
channels [149]; therefore, there is no need to create orifices for drug to be released. Another
