Fabrication and Characterization of Tedizolid Phosphate Nanocrystals for Topical Ocular Application: Improved Solubilization and In Vitro Drug Release

Abstract

Positively charged NCs of TZP (0.1%, w/v) for ocular use were prepared by the antisolvent precipitation method. TZP is a novel 5-Hydroxymethyl-Oxazolidinone class of antibiotic and is effective against many drug-resistant bacterial infections. Even the phosphate salt of this drug is poorly soluble, therefore the NCs were prepared for its better solubility and ocular availability. P188 was found better stabilizer than PVA for TZP-NCs. Characterization of the NCs including the particle-size, PDI, and ZP by Zeta-sizer, while morphology by SEM indicated that the preparation technique was successful to get the optimal sized (151.6 nm) TZP-NCs with good crystalline morphology. Mannitol (1%, w/v) prevented the crystal growth and provided good stabilization to NC1 during freeze-drying. FTIR spectroscopy confirmed the nano-crystallization did not alter the basic molecular structure of TZP. DSC and XRD studies indicated the reduced crystallinity of TZP-NC1, which potentiated its solubility. An increased solubility of TZP-NC1 (25.9 µgmL−1) as compared to pure TZP (18.4 µgmL−1) in STF with SLS. Addition of stearylamine (0.2%, w/v) and BKC (0.01%, w/v) have provided cationic (+29.4 mV) TZP-NCs. Redispersion of freeze-dried NCs in dextrose (5%, w/v) resulted in a clear transparent aqueous suspension of NC1 with osmolarity (298 mOsm·L−1) and viscosity (21.1 cps at 35 °C). Mannitol (cryoprotectant) during freeze-drying could also provide isotonicity to the nano-suspension at redispersion in dextrose solution. In vitro release in STF with SLS has shown relatively higher (78.8%) release of TZP from NC1 as compared to the conventional TZP-AqS (43.4%) at 12 h. TZP-NC1 was physically and chemically stable at three temperatures for 180 days. The above findings suggested that TZP-NC1 would be a promising alternative for ocular delivery of TZP with relatively improved performance.

Novel tetrahydrocurcumin integrated mucoadhesive nanocomposite κ-carrageenan/xanthan gum sponges: a strategy for effective local treatment of oral cancerous and precancerous lesions

“…In Figure 6(c) , the THC release rate from THC-NC-S (S10 and S12) was compared with THC-S (S11 and S13) and free THC-NC, as well. The release profile of THC-NC clearly showed a fast release of 95% within 15 min, which was contributed to the smaller size of NC that provided an overall increased surface area (Kalam et al., 2022 ). While THC-NC-S showed biphasic pattern of drug release with an initial rapid release up to 8 h and followed by a sustained slower phase where 90% of THC was released over 4 days.…”

Perspectives of Positively Charged Nanocrystals of Tedizolid Phosphate as a Topical Ocular Application in Rabbits

“…The characterization parameters included the size, polydispersityindex, zetapotential, structural morphology by scanning electron microscopy, FTIR for any interaction with the excipients, crystallinity by differential scanning calorimetry and X-ray diffraction studies, physicochemical characterization of the NCs for ocular suitability, saturation solubility, in vitro drug release in simulated tear fluid and storage stability at three different temperatures for 6 months. The data regarding these experiments have been published as a separate article in another journal [ 37 ]. For the ease of the reader, here we have included the composition of the formulations as mentioned in Table 1 .…”

“…In the present study, we investigated the in vitro antimicrobial efficacy of TZP-NCs against certain strains, the ocular irritation potential (if any) of NCs, the ocular pharmacokinetics of TDZ in rabbit eyes andthe ex vivo transcorneal permeation (through excised rabbit cornea) of TZP-NCs as compared to the conventional TZP-aqueous suspension (TZP-AqS). The developed TZP-NCs were characterized well andan in vitro release of TZP through the dialysis membrane was performed and reported in the previous part of this article [ 37 ]. The previously reported LC-MS/MS method was successfully utilized for the quantitative determination of TDZ in rabbit aqueous humor samples.…”

Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases

“…They also include improved ocular safety, increased formulation retention in cul-de-sac, and enhanced ocular permeation [ 152 ]. A number of medications used ocularly have been transformed into nanocrystals ( Table 1 ) with enhanced properties, and these include dexamethasone [ 348 ], itraconazole [ 349 ], tedizolid [ 350 ], and brinzolamide [ 227 ]. Moreover, Novartis Pharmaceutical Corporation’s formulation of nepafenac nanocrystals received approval for commercial release (FDA, 2012) under the brand name Ilevro ® .…”