Nanotechnology is a recent approach to construction and understanding the properties of matter also in the pharmaceutical field. The field of pharmaceutical nanotechnology represents mainly preparation of nanosystems, among which nanolayers and nanoparticles are classified. Nanolayers are often used to change surface properties and nanoparticles are used to achieve better bioavailability or controlled and targeted delivery of active ingredients. The purpose of our work was to produce and characterize the nanolayer of chitosan and alginate on micronized particles. In the second part of this doctoral dissertation we developed and evaluated nanosuspensions of celecoxib and orlistat which were also used in the preparation of solid oral dosage forms. Layer-by-layer self-assembly technique was used to form a nanolayer of chitosan and alginate layers on microparticles of ibuprofen. The formation of individual polyelectrolyte layers was inspected by measuring the zeta potential, and finally, the coated and non-coated particles have been investigated by optical microscopy and scanning electron microscopy. Celecoxib belongs to a class of drugs with selective COX-2 inhibition and exhibits poor solubility and high permeability. Therefore we can increase the dissolution rate and bioavailability with decreasing particle size. The combination of the emulsion-diffusion method with high pressure homogenization and suitable stabilizers.
was used for the preparation of celecoxib nanosuspension with an average particle size
from 300–350 nm. The spray drying was used to convert nanosuspension to powdery
form, which was mixed with microcrystalline cellulose and compressed into tablets. In
doing so, we monitored the parameters of the compression and found that by pressing
the nanoparticles, lower compression forces were needed to reach appropriate tensile
strength. The cristallinity of nano-sized celecoxib was confirmed with differential
scanning calorimetry and x-ray powder diffraction. Scanning electron microscopy was
used to evaluate size and morphology of particles. Finally dissolution rate of
nanosuspension and tablets with the nanosized particles was significantly higher in
comparison to forms with micro-sized drug.
Orlistat is a locally acting gastrointestinal lipase inhibitor and is used to treat
obesity, which is becoming a growing problem of modern society. The meltemulsification
method with high pressure homogenisation was used to prepare the nanosuspension of orlistat. By choosing an appropriate stabilizer and high pressure
homogenization conditions, we prepared nanosuspension with an average particle size
around 250 nm which was converted to dry powder by spray drying. The spray dried
product was filled in solid gelatine capsules. Dissolution tests in various media showed
significantly higher dissolution rate of the dosage form with nanonized substance in
compparison to other tested forms. Comparative, dissolution rate was determined also
for raw substance, physical mixture of active ingredient with excipients and drug,
already available on the market. In addition to classical dissolution rate of all the above
formulation, we determined the in vitro lipase inhibition, which was the highest in the
case of formulations with nanonized substance. The results suggest that adequate effect
could potentially be achieved with lower dose of nanosized orlistat which could also
reduce dose-dependent side effects.
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