SARS-CoV-2 Main protease (Mpro) is a well-known drug target against SARS-CoV-2 infection. Identification of Mpro inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify Mpro inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against Mpro. Among them, 10 drugs were found to be interacting with Mpro, including diltiazem HCl (1), mefenamic acid (2), losartan potassium (3), mexiletine HCl (4), glaucine HBr (5), trimebutine maleate (6), flurbiprofen (7), amantadine HCl (8), dextromethorphan (9), and lobeline HCl (10) in STD-NMR spectroscopy. Their interactions were compared with three standards (Repurposed anti-viral drugs), dexamethasone, chloroquine phosphate, and remdesivir. Thermal stability of Mpro and dissociation constant (Kd) of six interacting drugs were also determined using DSF. RMSD plots in MD simulation studies showed the formation of stable protein-ligand complexes. They were further examined for their antiviral activity by plaque reduction assay against SARS-CoV-2, which showed 55-100 % reduction in viral plaque. This study demonstrates the importance of drug repurposing against emerging and neglected diseases. This study also exhibits successful application of STD-NMR spectroscopy and plaque reduction assay in rapid identification of potential anti-viral agents.

This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The 1H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.

Necrotizing sialometaplasia is a rare, reactive, self-limiting disorder affecting a minor salivary gland that clinically mimics malignancy. Chronic smoking, alcohol use, trauma to the hard palate caused by local anesthetic injection due to the vasoconstrictive action of adrenaline in local anesthetic, topical application of nonsteroidal anti-inflammatory drugs like flurbiprofen spray used in bronchial asthma, oral intubation procedures for general anesthesia, ill-fitting dentures, bulimia nervosa, and minor salivary gland tumors are some of the contributing factors linked to its development. In this article, we discuss a rare, reactive, self-limiting condition affecting minor salivary gland, necrotizing sialometaplasia that occurred on the right posterolateral hard palate region in a 57-year-old male chronic smoker, diagnosed by oral medicine specialist by clinical findings and radiological evaluation by cone beam computed tomography that healed rapidly in three days by itself without any treatment, that prevented unwanted biopsy or surgery.

Herein, we report the obtaining of new hybrid molecules of amphetamine with different profens (amfens). The obtained amfens are characterized by their melting points, UV, 1H-, 13C-NMR, and HRMS spectra. A complete and detailed mass spectral analysis of the newly obtained derivatives of amphetamine with ibuprofen, flurbiprofen, ketoprofen, naproxen, and carprofen was performed. In vitro inhibition of albumin denaturation of each new compound was assessed, and they showed significant activity. The IC50 values of the obtained amphetamine-profen derivatives ranged from 92.81 to 159.87 µg/mL. This indicates that the new hybrids inherit the anti-inflammatory properties of profens. Using in silico method, the toxicity was also calculated. The obtained results are given in LD50 values. Depending on the route of administration, the amfens are less toxic compared to the standard amphetamine.

A nonsteroidal drug called flurbiprofen (FBN) has analgesic, anti-inflammatory and antipyretic activity. Currently the determination of FBN in cataplasm does not have any pharmacopeial method. However, the drug substance, tablet and ophthalmic solution formulations do have pharmacopeial methods. The development and validation of an accurate, precise and stability-indicating analytical method for the determination of FBN in cataplasm formulations is reported. The gradient method was employed for the quantification of FBN in the presence of internal standards such as biphenyl. A nonpolar separation phase (C18 , 250 × 4.6 mm, 5 μm Inertsil column; GL Sciences) was used. The optimal flow rate, column oven temperature, injection volume and detector wavelengths were 1.0 ml/min, 40°C, 20 μl and 245 nm, respectively. Mobile phase A was a mixture of water and glacial acetic acid (30:1 v/v) pH adjusted to 2.20 with glacial acetic acid or 1 m NaOH; mobile phase B was methanol (100%). The gradient elution program was [time (min)/% B]: 5/60, 20/70, 25/70, 30/60 and 40/60. The obtained RSDs for the precision and intermediate precision were 0.7 and 0.5%. The percentage recovery ranged from 99.2 to 100.4%. The linear regression coefficient >0.9996 indicates that all peak responses were linear with the concentration. The sample and standard solutions were stable for up to 24 h on the benchtop and in the refrigerator. The critical peaks were well separated from the generated peaks owing to forced degradation, including diluent and placebo peaks. The method validation data and quality by design-based robustness study results indicate that the developed method is robust and fit for routine use in the quality control laboratory. The proposed method is specific, accurate and precise, and the quality by design utilized the first method for the determination of FBN in cataplasm formulations. Transdermal patches and gels have low extraction capacity and this method is applicable for quantification.

A novel series of twenty two flurbiprofen amides (1-22) were designed and synthesized in good to excellent yields by reacting flurbiprofen acid with various aromatic/aliphatic primary amines in the presence of 1,1‑carbonyldiimidazole (CDI) in basic medium using acetonitrile as solvent. Structures of the synthesized derivatives were elucidated with the help of HR-ESI-MS, 1H-, and 13C NMR spectroscopy and finally screened them for their in-vivo anti-inflammatory potential using carrageenan induced mice paw oedema assay. Among the series, four compounds (8, 14, 15, and 20) displayed excellent activity ranging from 59.0 to 77.7 % decrease, while eight compounds (1, 3, 7, 10, 12, 13, 17, and 18) exhibited good activity in the decrease range of 37.0-50.0 %. Additionally, four compounds (2, 6, 16, and 22) attributed less activity, while the remaining six compounds (4, 5, 9, 11, 19, and 21) were found to be inactive. Furthermore, the In-silico studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of prostaglandin endoperoxide-synthase II enzyme.

Oral jelly is a semisolid preparation that could resolve problem associated with dosage form's swallowing, especially in pediatric and elderly ones. This work aimed to prepare oral flurbiprofen (FBP) jelly to improve patient compliance. Heating and congealing method was used to prepare FBP jelly using three different polymers (pectin, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose). The effect of different concentrations of pectin and sucrose on jelly properties was studied. The results revealed that both pectin and sodium carboxymethyl cellulose polymers gave acceptable jelly appearance and consistency. It was also observed that the increase of pectin or sucrose concentration had a significant impact on jelly viscosity. All pectin jellies except formula containing 5.5% pectin and 50% weight by volume (w/v) sucrose exhibited more than 50% and 85% of FBP releasing within 15 and 30 min, respectively. The formula (FP2) consisting of 4.5% pectin and 40% w/v sucrose was selected as optimum formula which had a high percent dissolution efficiency (78.95%) and better consistency during handling. This work succeeded in the preparation of new FBP oral jelly, which can be considered a promising dosage form for enhancement of patient compliance and drug solubility.

Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB1 and CB2 appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (7-11) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50-80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by N-methylation of the amide group. The compounds presented good physicochemical properties in addition to stability to chemical (pH 2 and 7.4) and enzymatic (plasma esterases) hydrolysis and showed medium to high gastrointestinal and BBB permeabilities in the PAMPA assay. When subjected to functional testing on CB1- or CB2-transfected cells, compounds demonstrated an inverse agonist profile on CB2 receptors and the further characterization of compound LASSBio-2265 (11) revealed moderate binding affinity to CB2 receptor (Ki = 16 µM) with an EC50 = 0.36 µM (Emax = 63%). LASSBio-2265 (11) (at 1, 3, and 10 mg/kg p.o.) was investigated in the formalin test in mice and a remarkable analgesic activity in the late inflammatory phase was observed, suggesting it could be promising for the treatment of pain syndromes associated with chronic inflammatory diseases.

Eye drops represent 90% of all currently used ophthalmic treatments. Only 0.02% of therapeutic molecules contained in eye drops reach the eye anterior chamber despite their high concentration. The tear film efficiently protects the cornea, reducing access to the target. Thereby, the increase in the drug bioavailability and efficiency must come from the mucoadhesion optimization of the drug delivery system. The gold nanoparticles, used as a drug delivery system in this study, already showcased ultrastable and mucoadhesive properties. The goal was to study the gold nanoparticles' ability to release two specific ophthalmic drugs, flurbiprofen and ketorolac. The parameters of interest were those involving the loading conditions, the gold nanoparticles properties, and the release experimental conditions. The drug release was measured using an in vitro model based on dialysis bags coupled with UV-visible spectroscopy. Gold nanoparticles showed an ability to release different molecules, whether hydrophobic or hydrophilic, in passive or active drug release environments. Based on these preliminary results, gold nanoparticles could represent a promising drug delivery system for ketorolac and flurbiprofen when topically applied through eye drops.

In the present study, 28 acyl hydrazones (4-31) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like 1H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC50 = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC50 = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.

The purpose of this study was to investigate the effect of the physicochemical parameters of drugs on their own release behaviors in polyisobutylene pressure sensitive adhesive (PIB PSA), which provided a theoretical guidance for the application of PIB in transdermal drug delivery system (TDDS). Seven drugs with different physicochemical parameters including clonidine (CLO), flurbiprofen (FLU), diclofenac (DIC), ibuprofen (IBU), zolmitriptan (ZOL), lidocaine (LID), tulobuterol (TUL) and the mixed adhesive (7:3, w/w) of Oppanol® B 15 N (M.W. = 108,000 Da) and Oppanol® N 50 (M.W. = 565,000 Da) were selected for in vitro drug release and skin permeation studies. Regression analysis was used to study the relationship between physicochemical parameters and release behaviors. The release behaviors of drugs were a negative correlation with polarizability and dipole moment per molecular volume (μ/V), which represented van der Waals and dipole-dipole interaction, respectively. Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MDSC) and molecular dynamics simulation were used to provide molecular details of the interaction between the drug and PIB. The free volume and molecular mobility of PIB were characterized using mechanical property tests, rheology study, MDSC and molecular dynamics simulation. Based on the above results, drugs with high polarizability and μ/V had stronger van der Waals and dipole-dipole interaction with PIB, reducing the free volume and molecular mobility of PIB, so that the drug struggled to release from PIB. In addition, the diffusion activation energy of the drug was calculated by using the variable temperature release study to characterize the ease of drug release from the kinetic aspect. And the trends of in vitro drug release and skin penetration profiles were basically similar. Thus, it was thought that the physicochemical parameters of the drug played a vital role in the drug release behavior of PIB PSAs and would affect the skin penetration process, which provided a reference for the design and application of patches based on PIB PSAs in TDDS.

The unprecedented photochemical late-stage defluorinative gem-difluoroallylation of aryl sulfonium salts, which are formed site-selectively by direct C(sp2)─H functionalization, is herein disclosed. This method is distinguished by its mild reaction conditions, wide scope, and excellent site-selectivity. As showcase examples, a Flurbiprofen and Pyriproxyfen derivatives could be late stage C(sp2)─H gem-difluoroallylated with high yields. Experimental and computational investigations were conducted.

Opioid-free anaesthesia (OFA) may reduce opioid-related side effects such as postoperative nausea and vomiting (PONV) and hyperalgesia. This study aims to investigate the effects of balanced OFA on PONV and pain outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS).

A composite magnetic adsorbent was developed by embedding graphene quantum dots (GQDs), silica-modified magnetite (Fe3O4-SiO2), and mesoporous carbon (MPC) into a molecularly imprinted polymer (GQDs/Fe3O4-SiO2/MPC/MIP). The adsorbent was applied to extract nonsteroidal anti-inflammatory drugs (NSAIDs) in milk. The MIP was formed via a sol-gel copolymerization using flurbiprofen, diflunisal, and mefenamic acid as template molecules, 3-aminopropyltriethoxysilane as a monomer, and tetraethyl orthosilicate as a cross-linker. GQDs and MPC enhanced affinity binding between NSAIDs and the adsorbent through π-π stacking, hydrogen bonding, and hydrophobic interaction. The Fe3O4-SiO2 nanoparticles embedded in the composite adsorbent enabled its rapid isolation from the sample solution. The extracted NSAIDs were quantified by high-performance liquid chromatography and exhibited good linearity from 1.0 to 100.0 μg L-1 for flurbiprofen and 0.5 to 100.0 μg L-1 for diflunisal and mefenamic acid, respectively. The limits of detection ranged from 0.5 to 1.0 μg L-1. Recoveries of NSAIDs from spiked milk samples ranged from 81.4 to 93.7%, with RSDs below 7%. The reproducibility of the fabricated adsorbent was good and in the optimal conditions, the developed adsorbent could be used for up to six extraction-desorption cycles.

Cunninghamella elegans is a well-studied fungus that biotransforms a range of xenobiotics owing to impressive cytochrome P450 (CYP) activity. In this paper, we report the biotransformation of 6:2 fluorotelomer alcohol (6:2 FTOH) by the fungus, yielding a range of fluorinated products that were detectable by fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Upon incubation with the pre-grown cultures, the substrate (100 mg/L) was completely consumed within 48 h, which is faster biotransformation than other fungi that have hitherto been studied. The main metabolite formed was the 5:3 fluorotelomer carboxylic acid (5:3 FTCA), which accumulated in the culture supernatant. When the cytochrome P450 inhibitor 1-aminobenzotriazole was included in the culture flasks, there was no biotransformation of 6:2 FTOH, indicating that these enzymes are key to the catalysis. Furthermore, when exogenous 5:3 FTCA was added to the fungus, the standard biotransformation of the drug flurbiprofen was inhibited, strongly suggesting that the main fluorotelomer alcohol biotransformation product inhibits CYP activity and accounts for its accumulation.

In comparison with RuII-arene compounds, the medicinal potential of homologous RuII-tpm compounds [tpm = tris(pyrazolyl)methane] is underexplored. Pyridine, 4-pyridinemethanol and four functionalized pyridines, synthesized from the esterification of 4-pyridinemethanol with bioactive carboxylic acids (i.e., ethacrynic acid, ibuprofen, flurbiprofen and naproxen), react with the precursor [RuCl(κ3-tpm)(PPh3)2]Cl (1) to afford [RuCl(κ3-tpm)(PPh3)(L)]Cl (2-7, L = pyridine ligand), in 78-91% yields. All products were fully characterized by HR-ESI mass spectrometry, IR and multinuclear NMR spectroscopy and the solid-state structures of two of the complexes, i.e. where L = pyridine and 4-pyridinemethanol, were ascertained by single crystal X-ray diffraction. The {Ru-tpm-PPh3} assembly is stable in D2O and in biological medium (DMEM) at 37 °C, with a tendency to slowly dissociate the pyridine ligand. The antiproliferative activity of the complexes was assessed on the cancerous A2780 and A2780cisR cell lines, and the nontumoral HEK 293T cell line; moreover inhibition assays were carried out on the complexes towards COX-2 and GSTP1 enzymes.

Background In this retrospective study, we aimed to investigate the effect of chlorhexidine digluconate-flurbiprofen spray (Klorhex Plus® oral spray) on postoperative sore throat (POST) and hoarseness (POH) in patients undergoing rhinoplasty. Methodology Patients who underwent rhinoplasty alone in our clinic between April 01, 2021, and February 28, 2022, were enrolled in the study. Patients' demographics such as age, gender, height, and smoking status that could affect sore throat, difficult intubation, and operation time were recorded from the patients' files. Patients were grouped as those who received Klorhex Plus oral spray before the surgery (Klorhex P group) and those who did not (control group). POST and POH were recorded from the patients' postoperative surgery files. Postoperative pain evaluation was performed using the Numerical Rating Scale (NRS) at the postoperative first hour (PPL1h), 12th hour (PPL12h), and first day (PPL1d) from the postoperative nursing files. Results A total of 354 patients who underwent rhinoplasty alone were included in this study. No significant difference was found between the groups in terms of the demographic data. Statistically, PPL1h, PPL12h, and PPL1d were significantly lower in the Klorhex P group compared to the control group (for all, p < 0.001). POST and POH were also significantly higher in the control group (both, p < 0.001). Conclusions The results of this study indicate that Klorhex Plus oral spray is an efficient agent for preemptive analgesia before rhinoplasty. It significantly decreases the postoperative pain level, POST, and POH. However, further comprehensive prospective studies are needed to introduce Klorhex Plus oral spray to rhinology practice.

Purpose: Intravenous patient-controlled analgesia (IV-PCA) has been widely used; however, regimen criteria have not yet been established. In China, the most often used opioid is sufentanil, for which repeated doses are a concern, and empirical flurbiprofen axetil (FBP) as an adjuvant. We hypothesized that hydromorphone would be a better choice and also evaluated the effectiveness of FBP as an adjuvant. Methods: This historical cohort study was conducted in two tertiary hospitals in China and included 12,674 patients using hydromorphone or sufentanil for IV-PCA between April 1, 2017, and January 30, 2021. The primary outcome was analgesic insufficiency at static (AIS). The secondary outcomes included analgesic insufficiency with movement (AIM) and common opioid-related adverse effects such as postoperative nausea and vomiting (PONV) and dizziness. Results: Sufentanil, but not the sufentanil-FBP combination, was associated with higher risks of AIS and AIM compared to those for hydromorphone (OR 1.64 [1.23, 2.19], p < 0.001 and OR 1.42 [1.16, 1.73], p < 0.001). Hydromorphone combined with FBP also decreased the risk of both AIS and AIM compared to those for pure hydromorphone (OR 0.74 [0.61, 0.90], p = 0.003 and OR 0.80 [0.71, 0.91], p < 0.001). However, the risk of PONV was higher in patients aged ≤35 years using FBP (hydromorphone-FBP vs. hydromorphone and sufentanil-FBP vs. hydromorphone, OR 1.69 [1.22, 2.33], p = 0.001 and 1.79 [1.12, 2.86], p = 0.015). Conclusion: Hydromorphone was superior to sufentanil for IV-PCA in postoperative analgesia. Adding FBP may improve the analgesic effects of both hydromorphone and sufentanil but was associated with an increased risk of PONV in patients <35 years of age.

Ionic liquids (ILs) have been proven to be an efficient technology for enhancing drug skin permeability. However, the question of whether the two components of ILs are released synchronously in transdermal preparations has remained unclear. Thus, this study aimed to investigate the release characteristics of two components of ILs and their underlying molecular mechanism. The ILs containing flurbiprofen (FLU) and lidocaine (LID) were synthesized and characterized. The four typical acrylates pressure sensitive adhesives (PSAs) with different functional groups were synthesized and characterized. The effects of PSAs on the release characteristics of two components of ILs were investigated by drug release tests and verified by skin permeation experiments. The action mechanisms were revealed by FTIR, Raman, dielectric spectrum, and molecular docking. The results showed that the average release amount of FLU (0.29 μmol/cm2) and LID (0.11 μmol/cm2) of ILs in the four PSAs was significantly different (p < 0.05), which illustrated that the two components did not release synchronously. The PSA-none and PSA-OH with low permittivity (7.37, 9.82) interacted with drugs mainly by dipole-dipole interactions and hydrogen bonds. The PSA-COOH and PSA-CONH2 with high permittivity (11.19, 15.32) interacted with drugs mainly by ionic bonds and ionic hydrogen bonds. Thus, this study provides scientific guidance for the application of ILs in transdermal preparations.

We report the use of a hyphenated HPLC-DAD(diode array detector)-HRMS/SPE NMR system for the separation and isolation of a complex mixture of esters, containing substances with very similar LC retention times. The literature known mono- and diesters of the drug Flurbiprofen and polyethylene glycol, which form a large number of substances with varying chain lengths, were chosen for this study. We demonstrate the use of this hyphenated system to quickly and effectively isolate sixteen of these highly similar individual esters in an automated fashion, demonstrating its applicability in standard pharmaceutical analysis and quality control of drugs. Both, synthetic solutions of these esters and extracts from Flurbiprofen lozenges were used for this purpose. By the sole use of this system, the individual compounds were isolated and UV, HRMS and 1D and 2D NMR data could be collected, enabling the identification and differentiation of the individual esters.

In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid-coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200-400 kDa and the concentration of HA solution was 1.25 mg·mL -1, the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of - 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (Cmax) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (Cmax) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system.