Nanosuspensions as Nanomedicine: Current Status and Future Prospects
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
Another special feature of nanosuspensions is the absence of Ostwald ripening, which is suggestive of their long-term physical stability [26]. Ostwald’s ripening [27, 28] has been described for ultrafine dispersed systems and is responsible for crystal growth and subsequently forming of microparticles. Ostwald ripening is caused by the differences in dissolution pressure/saturation solubility between small and large particles. The lack of Ostwald’s ripening in nanosuspensions is attributed to their uniform particle size, which is created by various manufacturing processes. The absence of particles with large differences in their size in nanosuspensions prevents the existence of the different saturation solubilities, which, in turn, prevents the Ostwald’s ripening effect. Also, stabilizers employed for nanosuspension render them physically stable through their shelf life [22]. However, with the progress in this field, many stability issues have been faced by the formulators that are discussed later in this chapter.
Nanomedicines for Ocular NSAIDs: State-of-the-Art Update of the Safety on Drug Delivery
Lajos P. Balogh in Nano-Enabled Medical Applications, 2020
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
Danilo D. Lasic in 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.
Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery
Published in Expert Opinion on Drug Delivery, 2018
Viral Patel, Om Prakash Sharma, Tejal Mehta
The bottom-up approach is a classical precipitation method which incorporates the basic principle of precipitation. The drug is dissolved in a solvent which is added to a nonsolvent, resulting in precipitation of the drug [128]. The critical requirements in this technology are size of crystals and the crystallinity of particles developed. It becomes necessary to control the crystalline nature of growing particles because amorphous nanocrystals have higher solubility in comparison to their crystalline counterpart. Uncontrolled crystal growth will result in Ostwald ripening. The variants of bottom-up technologies are sonocrystallization, high gravity-controlled precipitation, liquid jet precipitation, multiinlet vortex mixing, rapid expansion of supercritical solution (RESS), supercritical antisolvent, and evaporative precipitation into aqueous solution [126,129,130].
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.
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