Optimization of a Cefuroxime Axetil-Loaded Liquid Self-Nanoemulsifying Drug Delivery System: Enhanced Solubility, Dissolution and Caco-2 Cell Uptake

Abstract

Cefuroxime axetil (CA) is an oral cephalosporin which hydrolyzes rapidly to the active parent compound cefuroxime. CA is known to have incomplete oral bioavailability (30–50%) due to its poor solubility and enzymatic conversion to cefuroxime in the gut lumen. In order to overcome these drawbacks, a lipid-based self-nanoemulsifying drug delivery system (SNEDDS) has been developed and optimized. The SNEDDS formulations were prepared using the aqueous phase titration method. The greatest self-emulsifying area was found in the 2:1 Smix ratio. As a result, different SNEDDS formulations were carefully selected from this phase diagram based on their smaller droplet size < 100 nm, polydispersity index ≤ 0.5, dispersibility (Grade A), and transmittance (%) > 85%. Thermodynamic stability tests were carried out in order to rule out any metastable/unstable SNEDDS formulations. The droplet size, polydispersity index, zeta potential, and entrapment efficiency (% EE) of optimized CA-loaded SNEDDS (C-3) were 18.50 ± 1.83 nm, 0.064 ± 0.008, −22.12 ± 1.20 mV, and 97.62 ± 1.06%, respectively. In vitro release studies revealed that the SNEDDS formulation had increased CA solubility. CA-SNEDDS-C3 increased CA cellular uptake, possibly due to increased CA solubility and the inhibition of enzymatic conversion to cefuroxime. Finally, in terms of the improvement of oral bioavailability, CA-loaded-SNEDDS could be a viable alternative to commercially available CA formulations.

RP HPLC Enabled Novel Analytical Method for the Development and Quantification of Cefuroxime Axetil in its Bulk Drug and Pharmaceutical Formulations

“…A prepared mixture of HPLC grade methanol and water (50:50% v/v) was utilized as a diluent throughout the investigation. [14,15]…”

Development of Linagliptin Ultra Fine Solid Supersaturated Bio-SNEDDS Using Triangular Mixture Design for Enhancement of Oral Bioavailability: Impact of P-gp Inhibition

“…This phenomenon can be elucidated by means of surface associated drug, small particle size of the nanodroplets formed and high surface area. This initial fast release was followed by slower sustained release pattern, which may be attributed to controlled diffusion of the drug from the nanoparticles [41]. The resulted data of both optimized formulations (F4 and F8) were fitted to different kinetic models such as zero order, first order, Higuchi and Korsermeyer-Peppas models to comprehend the kinetics of release.…”

Effective Treatment of Haemophilus influenzae-Induced Bacterial Conjunctivitis by a Bioadhesive Nanoparticle Reticulate Structure

“…In terms of bacterial conjunctivitis treatment, the current medical consensus includes applying topical antibiotics preparations to accelerate the healing process, preventing human-to-human transmission and reducing reinfection rates. , As a semi-synthetic prodrug, cefuroxime axetil (CA) exerts its antibacterial activity by hydrolyzing into cefuroxime in vivo which has a great antibacterial effect against HIN . It is commonly applied for the treatment of pharyngitis, tympanitis, and acute bacterial maxillary sinusitis to name a few. , However, the biopharmaceutical obstacles of CA including poor solubility, poor permeability onto biofilms, and high frequency of administration limit its use for ocular drug delivery. , …”

“…23,24 However, the biopharmaceutical obstacles of CA including poor solubility, poor permeability onto biofilms, and high frequency of administration limit its use for ocular drug delivery. 25,26 To address above challenges of conventional eye drops, researchers have developed novel ophthalmic drug delivery systems, such as nanosuspensions, 27,28 nanostructured lipid carriers, 29,30 preformed gels, 13,31,32 and so forth. 15 Among these, nanotechnology has an extensive diversity of applications in ophthalmology.…”