Biomedical Engineering Reference
In-Depth Information
by more Eudragit RL because it is more hydrophilic. Together with HPMC, Wei Wu et al.
[138] added lactose to form a coating by compression coating technique. Lactose readily
dissolves out when in contact with water, leaving a diffusion path for drug to be released.
Therefore, a faster release and shorter lag time were observed for higher lactose content,
but a linear release profile was observed regardless of lactose content. A similar idea is
widely used for polyvinyl-based polymers to alter the drug release rate. It is rather a com-
mon practice to blend hydrophobic polymers with hydrophilic polymers such as cellulose
derivatives to tailor drug release behavior (Table 5.2). Besides the fact that blendings of
different polymers could affect the overall hydrophilicity of the coating, the hydrophilic
constitutes could dissolve and leach out from the coating when in contact with the body
fluid, hence leaving diffusion channels for the core material to be released [139]. Hence,
both porous and nonporous descriptions of the diffusion process are needed to describe
the drug release behavior of certain coatings.
In practice, release rate in erosion controlled drug delivery system is mainly controlled
by degradation rate of the coating. Therefore, most research has been devoted to design
polymers with different degradation rates. Mather and coworkers [140] studied the release
behavior of a family of nanostructured hybrid polyurethanes, which was synthesized by
covalently connecting polyhedral oligosilsesquioxane thermoplastic polyurethanes and
biodegradable soft segments of poly-d,l-lactide/caprolactone copolymer with incorpora-
tion of PEG. It was found out that the release rate could be easily tailored from half a day
to 90 days by altering the polymer structure.
HPMC can be used as both matrix and coating materials. Uncoated HPMC usually
shows a linear release profile (zero-order release profile), and its release rate can be reduced
by applying Eudragit RS 30D coating at different levels: the higher the coating level, the
smaller the release rate is. Drug molecules can be dispersed in the core and coating at the
same time (dual-drug loaded) to have more complex release profiles. It was reported that
at moderate coating levels, a biphase release profile is observed with a faster release rate
in the first few hours followed by a slower release rate [141]. Maroni and coworkers [142]
manufactured insulin tablets coated with HPMC. It was found that the insulin tablets
could be manufactured by an industrial method: direct compression without loss of func-
tionality. Because the major challenge in oral insulin delivery (and other acidic sensitive
drugs, such as Omeprazole) is to protect the insulin from degradation until it reaches the
TABLE 5.2
Cellulose Derivatives as Coating Materials
Polymer
Property
Methylcellulose (MC)
Soluble in cold water
Ethylcellulose
Soluble in organic solvents, but insoluble in water.
Used to realize sustained release formulation.
Used together with water-soluble celluloses to
alter the release behavior
Hydroxyethylcellulose (HEC)
Soluble in water
Methyl hydroxyethylcellulose (MHEC)
Soluble in water
Hydroxypropyl cellulose (HPC)
Soluble in water, but tacky when dried
HPMC
Soluble in water, alcohols, and halogenated
hydrocarbons
Source:
Gibson, M., Pharmaceutical Preformulation and Formulation: A Practical Guide From
Candidate Drug Selection to Commercial Dosage Form, 2007.
