Biomedical Engineering Reference
In-Depth Information
techniques, the drug is dissolved in the lipid that is melted at approximately
5-108 °C above its melting point.
Procedure for Hot homogenization technique
(1)
Melt the lipid at 5 ± 108 °C above its melting point.
(2)
Add the drug and stir the drug-containing melt to disperse in a hot aqueous
surfactant solution.
(3)
Homogenize the resulting pre-emulsion with a piston-gap homogenizer
(e.g. Micron LAB40).
(4)
Cool down the hot oil in water nanoemulsion to RT to allow the lipid to
recrystallize into solid lipid NPs. In the case of glycerides being composed
of short-chain fatty acids (e.g. Dynasan 112) and glycerides with a low
melting point (too close to RT), it might be necessary to cool the nanoemul-
sions to even lower temperatures to initiate recrystallization. In some cases,
lyophilization may be used for recrystallization.
The hot homogenization technique may be applied to drugs showing slight
temperature sensitivity because the exposure to an increased temperature is
relatively short. For highly temperature-sensitive compounds, the cold homog-
enization technique is the loading choice. This is also necessary when formu-
lating hydrophilic drugs because during the hot homogenization process, they
would partition between the lipid melt and the water phase.
Procedure for Cold homogenization technique
(1)
Melt the lipid at 5 ± 108 °C above its melting point.
(2)
Add the drug and stir until homogeneous.
(3)
Cool the lipid melt containing the drug until it solidifies.
(4)
Ground the lipid microparticles (~50 ± 100 mm).
(5)
Disperse these lipid microparticles in a cold surfactant solution to form a
presuspension.
(6)
Homogenize the presuspension at or below RT with a cavitation force that is
strong enough to break the lipid particles directly to create solid lipid NPs. This
avoids and/or minimizes the melting of the lipid and therefore minimizing the
loss of hydrophilic drugs to the water phase. It is necessary that the difference
between the melting point of the lipid and the homogenization temperature
needs to be large enough to avoid melting the lipid in the homogenizer. Note
that the homogenization process itself increases the mixture temperature (e.g.
10-20 °C per homogenization cycle), and in addition, there are temperature
peaks in the homogenizer. One way to minimize the loss of hydrophilic com-
pounds to the aqueous phase of the solid lipid NP dispersion is to replace the
water with low-solubility liquids for the drug like oils or PEG 600. Encapsulation
of solid lipid NPs in oil or PEG 600 is advantageous for oral drug delivery
because this dispersion could be directly converted into soft gelatin capsules.
One example of a drug that had been nanocarrier encapsulated is cisplatin.
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Cisplatin is a chemotherapeutic agent that is widely used for the treatment of
