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Drug Nanocrystals
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
M. Ermelinda S. Eusébio, Ricardo A. E. Castro, Joäo Canotilho
Ostwald ripening is another potential source of physical instability for nanosuspensions [132]. Due to the tendency of a solid phase to achieve the minimum surface Gibbs energy, particle growth will occur in nanosuspensions, resulting from saturation solubility differences between smaller and larger particles: saturation solubility increases as particle size decreases (Eq. 7.2, for spherical particles), such that smaller particles tend to dissolve whereas larger ones grow due to diffusional mass exchange. The relevance of the Ostwald ripening increases with higher polydispersity index (PDI).
Nanomedicines for Ocular NSAIDs: State-of-the-Art Update of the Safety on Drug Delivery
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Joana R. Campos, Joana Araújo, Elisabet Gonzalez-Mira, Maria A. Egea, Elena Sanchez-Lopez, Marta Espina, Selma B. Souto, Maria L. Garcia, Eliana B. Souto
Several drugs (e.g. cinnarizine, griseofulvin, indomethacin, itraconazole, loviride, mebendazole, naproxen, phenylbutazone, and phenytoin) have been formulated as nanocrystals for the evaluation of the Ostwald ripening effect as a function of the storage temperature [157]. Except for indomethacin, after 3 months of storage at room temperature, Ostwald ripening occurred in all drugs. Lower temperatures were able to slow down the ripening whereas higher temperatures accelerated the effect. Lyophilization and spray-drying also affected particle agglomeration in particular for drugs with more hydrophobic surfaces, which were harder to disintegrate, and thus dissolution was compromised upon drying. The same was found for compounds having higher log P values. Drug nanocrystals can be considered as a universal formulation approach for poorly soluble drugs. The striking advantages the advantages of nanocrystals for drug delivery to the eye are: improved ocular safety, increased retention of the formulation in cul-de-sac, enhanced corneal permeability across the corneal and conjunctival epithelium, enhanced ocular bioavailability, dual drug release profile in the eye, and increased tolerability [152].
Liposomes
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
Ostwald ripening is another mechanism for the destabilization of colloidal systems. Colloidal particles are in equilibrium with their building blocks free in solution. Solubility of molecules or ions on surfaces with higher curvature is larger than on surfaces with lower radius of curvature. The reassociation of desorbed ions or molecules with colloidal particle scales with the surface area of the adsorbing particle and therefore it is normally said “the rich get richer and the poor get poorer.” In conventional liposomes this is not a very important mechanism because of low lipid solubility. However, in systems with highly charged lipids this may be different (Lasic, 1993a).
Utilization of a nanostructured lipid carrier encapsulating pitavastatin–Pinus densiflora oil for enhancing cytotoxicity against the gingival carcinoma HGF-1 cell line
Published in Drug Delivery, 2023
Raed I. Felimban, Hossam H. Tayeb, Adeel G Chaudhary, Majed A. Felemban, Fuad H. Alnadwi, Sarah A. Ali, Jazia A. Alblowi, Eman ALfayez, Deena Bukhary, Mohammed Alissa, Safa H. Qahl
As per the obtained formula, factor A had a nonsignificant effect on the stability index, while factors B and C exerted a significantly negative effect on the same parameter (p < .0001). The decrease in stability with the increase in factor B could be due to the expected decrease in the rigidity of the produced NLCs because the amount of Ovucire® would have been lowered; this lipid keeps particles hard and decreases the chance of particles to fuse and become agglomerated; hence, it preserves particles’ stability (Azhar Shekoufeh Bahari & Hamishehkar, 2016) and thus its decrease would result in a low stability. The unexpected decrease in the stability index with the increase in the Labrasol® ratio might be explained by the Ostwald ripening phenomenon, in which there is the growth of larger particles at the expense of smaller ones due to the mass transfer of the dispersed phase into the surrounding dispersion medium (Ee et al., 2008). Some investigators have reported that the Ostwald ripening mechanism increases with the increase of surfactant concentration because the particle size becomes smaller following such an increase and, hence, more particles pass into the surrounding medium, contribute to the formation of larger particles, and eventually decrease the stability (Witayaudom & Klinkesorn, 2017). Figure 3 presents the main effect diagram and the contour and 3-D surface plots, which show the effect of the studied factors on the PV-Pd-NLCs stability index.
Overcoming hydrolytic degradation challenges in topical delivery: non-aqueous nano-emulsions
Published in Expert Opinion on Drug Delivery, 2022
Arya Kadukkattil Ramanunny, Sachin Kumar Singh, Sheetu Wadhwa, Monica Gulati, Bhupinder Kapoor, Rubiya Khursheed, Gowthamarajan Kuppusamy, Kamal Dua, Harish Dureja, Dinesh Kumar Chellappan, Niraj Kumar Jha, Piyush Kumar Gupta, Sukriti Vishwas
The differential density of droplets and the dispersion medium determines the stability issues. If the dispersed droplets possess lower density in comparison to the dispersion medium, they tend to move upward. This phenomenon is known as creaming. The droplets with higher density experience higher gravitational pull and move downward. This is termed as sedimentation. The difference in chemical potential that exists between droplets and the Laplace pressure generated at the curved interface explains the frequency of Ostwald ripening [111]. When the potential is higher in smaller droplets, the mass transfer occurs resulting in the larger droplet. The smaller droplets merge with larger once gradually with time, resulting in giant droplets. Ostwald ripening is a major issue faced in the formulation development [112]. The instability problems associated with nano-emulsions are briefly represented in Figure 2.
The effect of critical process parameters of the high pressure homogenization technique on the critical quality attributes of flurbiprofen nanosuspensions
Published in Pharmaceutical Development and Technology, 2019
Ayse Nur Oktay, Sibel Ilbasmis-Tamer, Nevin Celebi
The storage of nanosuspensions at low temperature may lead to recrystallization due to solubility reduction and particle size augmentation. In contrast, a high temperature may increase the solubility of particles, being therefore accompanied by particle size reduction. Due to the decrease of particle size, aggregation of particle and increase in the larger particle population (Ostwald ripening) may occur (Al Shaal et al. 2010, Ghosh et al. 2012). For this reason, the selection of a suitable type and amount of stabilizer to provide electrostatic and steric stabilization by means of covering of the particle surface is necessary (Beirowski et al. 2011, Tuomela et al. 2016, Van Eedenburgh et al. 2009). By using experimental design, the suitable ratio of stabilizer was successfully determined and the nanosuspension retained physically stability during 12 months of storage at 25 ± 2 °C and 6 months at 40 ± 2 °C.