This US technique is a dispersing technique, which was initially used for the production of solid lipid nanodispersion. The US based on the mechanism of cavitation. In the first step, the drug was added to previously melt solid lipid. In the second step, the heated aqueous phase (heated to the same temperature) was added to the melted lipid and emulsified by probe sonication or by using a high speed stirrer or aqueous phase added to the lipid phase drop by drop followed by magnetic stirring. The obtained pre-emulsion was ultrasonicated using a probe and a sonicator with a water bath (at 0oC). To prevent recrystallization during the process, the production temperature is kept at least 5oC above the lipid melting point. The obtained nanoemulsion (o/w) was filtered through a 0.45 μm membrane to remove impurities carried in during the US. Then they obtained SLN is stored at 4oC. To increase the stability of the formulation, was lyophilized by a lyophilizer to obtain freeze-dried powder and sometimes mannitol (5%) was added into SLNs as cryoprotector.
Fig.1 HSH method. (Nahum, 2021)
Reduced shear stress.
Spherically shaped and monodispersed NLCs were successfully prepared with C888 (solid lipid) and Mig (liquid lipid) using a combination of HSH and US techniques, where processing time and its impact on the properties of NLCs were also investigated. Varying the US processing time between 1 to 15 min allowed the design of particles with different sizes, PDI, and surface charges. The particle size obtained after HSH alone was found to be 148-191 nm depending on the ratio between solid and liquid lipids, which decreased to 118-164 nm after just 1 min of US. There was a minimal effect of longer HSH time on the properties of NLCs as 15 min of HSH did not result in the further reduction of particle size. There was a minimal effect of longer HSH time on the properties of NLCs as 15 min of HSH did not result in the further reduction of particle size. In general, the application of US led to a decrease in particle size after HSH but an increase in particle diameter of low Miglyol containing preparation was also observed with longer sonication time. OLZ was successfully encapsulated in the NLCs and a total release of 89% was achieved in 24 h in PBS at pH 7.4. Nonetheless, this could be concluded based on the data obtained from the study that US along with HSH can be an effective and fast method to prepare NLCs of varying particle sizes that can potentially improve the dissolution rate of BCS II drugs.
Fig.2 Effect of HSH time on the formulation of blank F30 NLCs. (Ajiboye, 2021)
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