Flurbiprofen Research Articles

Development of chitosan-graphene oxide blend nanoparticles for controlled flurbiprofen delivery

The use of natural polymeric nanoparticles (Nps) as drug carriers is a highly promising area of research in the field of drug delivery systems because of their high efficiency. In this study, flurbiprofen (FB) loaded chitosan-graphene oxide (CS-GO) blend Nps were synthesized as a controlled delivery system using the emulsion method. The crystalline, molecular, and morphological structures of the prepared CS-GO Nps were characterized using a variety of analytical methods, including Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-Ray diffractometry (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). It was found that the introduction of GO into the CS nanoparticle formulation increased its thermal stability. The range of the average particle size was between 362 ± 5.06 and 718 ± 2.21 nm, with negative zeta potential values between −7.67 ± 4.16 and − 27.93 ± 2.26 mV. The effects of the CS/GO ratio, the FB/polymer ratio, the amount of span 80, and the cross-linker concentration were assessed on FB release profiles. In vitro release studies displayed a two-stage release behaviour with a fast initial release of the FB, followed by sustained and extended release, and the incorporation of GO into the CS Nps made the FB release more sustained and controlled manner. Besides, the cytotoxicity test of the FB-loaded CS-GO Nps was studied through MTT assay, and it was found that they were biocompatible. Based on these findings, it can be inferred that the prepared CS-GO Nps might be a promising candidate drug carrier system for FB.

METHOD DEVELOPMENT AND VALIDATION OF FLURBIPROFEN SODIUM BY USING UPLC

A simple, precise, and accurate ultra-performance liquid chromatography was developed for flurbiprofen sodium on Acquity BEHC18, (50 x 2.1 mm, 1.7 µm) using acetonitrile: water: glacial acetic acid as the mobile phase. The flow rate was 0.2 mL min-1 and effluent was monitored at 254 nm. The retention time for flurbiprofen sodium was found to be 2.3. Developed method was validated for precision, accuracy, linearity range, robustness and ruggedness as per ICH guideline

Preparation and Study on the Single-Crystal Structure of Flurbiprofen–Salicylamide Co-crystal

AbstractCo-crystals can improve the physicochemical properties of pharmaceutical active ingredients, and thus have great potential in improving drug performance. Some studies have obtained the powder spectrum of the co-crystal of flurbiprofen (FBP) and salicylamide (2-OHBZA) but have not obtained a single-crystal structure. In this study, co-crystals of FBP-2-OHBZA with a molar ratio of 1:1 were obtained by slow evaporation using ethyl acetate and tetrahydrofuran for verification. Density functional theory was used to optimize the structure of the hydrogen bond and π−π stacking formed by the co-crystal of FBP and 2-OHBZA. The assay results of the co-crystals of FBP-2-OHBZA are in good agreement with the calculated values reported.

Evaluation of two different orally disintegrating tablet formulations containing flurbiprofen inclusion complex and its solid dispersion

Purpose: To prepare orally dispersible tablet formulations (ODTs) by increasing the solubility of flurbiprofen (FB), which has low water solubility. 
 Methods: The ODTs were prepared using direct compression method the inclusion complexes and solid dispersions with the highest solubility were further evaluated. Flurbiprofen, polyvinylpyrrolidone (PVP) solid dispersions were blended together by solvent evaporation method, while the inclusion complexes were co-formulated with beta cyclodextrin (β-CD) by kneading at three different ratios. The ODTs were characterized by differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR) and for their micromeritic properties. In addition, the solubility properties of the inclusion complexes and solid dispersions in distilled water were compared with the solubility of flurbiprofen. 
 Results: The highest solubility value of PVP-FB solid dispersions was found at 1:6 (0.501 mg/mL) and for FB β-CD inclusion complex at 1:2 (0.701 mg/mL). Angle of repose ranged from 28.09 – 32.15 (o); Carr’s index from 7.59 to 10.01; and Hausner’s ration from 1.05 – 1.15. DSC and spectral studies indicate that FB did not chemically interact with either PVP or β-CD. 
 Conclusion: Orally dispersible tablets containing flurbiprofen β-CD complex exhibit significantly higher bioavailability than the drug alone due to its increased solubility. 

Analgesics can affect the sensitivity of temozolomide to glioma chemotherapy through gap junction.

This study investigated the effect of frequently used analgesics in cancer pain management (flurbiprofen (FLU), tramadol (TRA), and morphine (MOR)) and a novel α2-adrenergic agonist (dexmedetomidine, DEX) on temozolomide (TMZ) sensitivity in glioma cells. Cell counting kit-8 and colony-formation assays were performed to analyze the viability of U87 and SHG-44 cell lines. A high and low cell density of colony method, pharmacological methods, and connexin43 mimetic peptide GAP27 were used to manipulate the function of gap junctions; "Parachute" dye coupling and western blot were employed to determine junctional channel transfer ability and connexin expression. The results showed that DEX (in the concentration range of 0.1 to 5.0ng/ml) and TRA (in the concentration range of 1.0 to 10.0µg/ml) reduced the TMZ cytotoxicity in a concentration-dependent manner but was only observed with high cell density (having formed gap junction). The cell viability percentage was 71.3 to 86.8% when DEX was applied at 5.0ng/ml, while tramadol showed 69.6 to 83.7% viability at 5.0μg/ml in U87 cells. Similarly, 5.0ng/ml of DEX resulted in 62.6 to 80.5%, and 5.0μg/ml TRA showed 63.5 to 77.3% viability in SHG-44 cells. Further investigating the impact of analgesics on gap junctions, only DEX and TRA were found to decrease channel dye transfer through connexin phosphorylation and ERK pathway, while no such effect was observed for FLU and MOR. Analgesics that can affect junctional communication may compromise the effectiveness of TMZ when used simultaneously.

Comprehensive characterisation of the flurbiprofen/β-cyclodextrin inclusion complex using X-ray techniques and NMR spectroscopy

A new pharmaceutical form of a nonsteroidal anti-inflammatory drug complex composed of racemic flurbiprofen (FP) with a macrocyclic compound, forming a guest-host complex, was investigated. As with the other propionic acid compound, ketoprofen, three methods (co-precipitation, evaporation and heating-under-reflux) were used to prepare the β-cyclodextrin (β-CD) complex with FP. 1HNMR and X-ray powder diffraction (XRPD) in solution and solid state, respectively, were used to monitor the guest-host interactions. Only the heating-under-reflux method turned out to be suitable for host-guest complex formation. For the prospective method, a complex was prepared in the form of a crystalline powder, which was used as a starting material for the preparation of monocrystals suitable for X-ray crystallographic studies. The selected crystal was used to collect the diffraction data, which enabled the crystal and the molecular structure of the complex to be solved. This work is a connecting element in understanding the complete view of the interaction of FP with β-CD, mainly due to the results obtained with the X-ray single-crystal diffraction technique.

Nanoscaled MnSnO2@CsPbBr3 quantum dots heterostructure photocatalyst as efficient organic pollutants degradation by peroxymonosulfate; DFT calculation

In this work, we developed a promising photocatalyst in CsPbBr3 quantum dots (QDs) because of their exceptional optoelectronic characteristics. However, QDs applications in the field of photocatalysis were mainly hampered by their poor stability and insufficient charge transfer efficiency. Herein, a novel and efficient MnSnO2@CsPbBr3 (MSO@QDs) nanocomposite was first time effectively designed and synthesized by a wet impregnation method for peroxymonosulfate (PMS) activation under the light. The newly generated interface phase of QDs between MnSnO2 (MSO) showed great potential to improve light absorption, leading to effective separation and transfer of photoelectron-hole pairs. This novel nanocomposite MSO@QDs showed great Flurbiprofen (FL) removal efficiency under the PMS/Light system. It should be noted that this nanocomposite removed 85.74% of FL in just 70 min, which was almost 1.11 and 2.51 times greater than using pure QDs and pure MSO, respectively. Based on thorough measurements of structural analysis, Brunauer-Emmett-Teller (BET), UV-vis spectra, electrochemical impedance spectroscopy (EIS), transient photocurrent response, and a potential mechanism for organic pollutants degradation over MSO@QDs nanocomposite was envisioned. The principal reactive species of photoinduced holes (h+), i.e. O2˙−, SO4˙−, ˙OH, and non-radical (1O2) were characterized via scavengers’ technique and electron paramagnetic resonance (EPR) measurements. The highest photocatalytic performance for the removal of MO, MB, and IBU was demonstrated by MSO@QDs nanocomposite/PMS, revealing their excellent ability to remove organic pollutants through photo-oxidation. Furthermore, the developed nanocomposite exhibited good stability in an aqueous medium. According to computational investigation using the density functional theory (DFT) method, the site's higher Fukui index f0 value corresponds to a greater propensity to be attacked by reactive species. This work offers a fresh perspective on developing further high-efficiency, low-cost photocatalysts for wastewater treatment.

Catalytic oxidation activation of peroxymonosulfate over Fe-Co bimetallic oxides for flurbiprofen degradation.

In this research, FeCo2O4 nanomaterial was successfully synthesized by a typical sol-gel method and conducted as an effective agent for peroxymonosulfate (PMS) activation to eliminate antibiotics flurbiprofen (FLU), a strong nonsteroidal drug. FeCo2O4 nanomaterial was characterized by XRD, TEM, SEM, and XPS. Various characterization results proved that FeCo2O4 held stable spinel structure. The interfering factors including initial pH, PMS concentration, catalyst dosage, inorganic anions, and humic acid on FLU removal were also discussed. The conclusion was that the removal efficiency of FLU reached 98.2% within 120min after adding FeCo2O4 (0.4gL-1) and PMS (3mM). The optimal pH for FLU degradation was the initial pH of 6.5; too acidic or alkaline was not conductive to the degradation. The existence of HA and Cl- restrained the degradation of FLU, and HCO3- promoted the removal, while the influence of NO3- and SO42- could not be considered. The radical scavenging experiment confirmed that •OH, O2•-, and SO4•- participated in FLU removal and SO4•- functioned a leading role. FeCo2O4 showed high efficiency for PMS activation in pH range of 3.0 to 10.0. After the fourth cycle operation, the FLU removal rate exceeded 76.9%, and the Co leaching rate was low during the catalytic reaction. This study shows that FeCo2O4 nanomaterial is an efficient and environment-friendly catalyst, which can be applied for PMS activation to remove organic pollutants in water.

Comparison of in vivo pharmacokinetic behaviors of R- and S-flurbiprofen after intravenous injection of flurbiprofen axetil.

Flurbiprofen axetil (FA) is a prodrug of flurbiprofen (FP), and it is hydrolyzed to the active FP by carboxylesterase in plasma after intravenous injection. The pharmacological action of FP is closely related to its chirality, and S-FP shows better analgesic effects than R-FP. Therefore, it is of great significance to compare the in vivo pharmacokinetic behaviors of R-FP and S-FP. In this study, we designed a sensitive high performance liquid chromatography-tandem mass spectrometry method and used CHIRALPAK-IG3 column for chiral separation to quantify the concentrations of R-FP and S-FP in rat plasma. The results show that this method can accurately and effectively analyze the contents of R-FP and S-FP in plasma. In addition, the systemic exposure was approximately 3.09-folds for the S-FP compared with the R-FP following intravenous administration of the FA to rats at a single dose of 4.5mg/kg. More importantly, the clearance rate of S-FP is significantly smaller than that of R-FP. Therefore, the development of S-FA injectable emulsion for clinical treatment of postoperative pain is very necessary.

Masking the Taste of Fixed-Dose Combination Drugs: Particular NSAIDs Can Efficiently Mask the Bitterness of Famotidine.

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.

QbD-based stability-indicating liquid chromatography (RP-HPLC) method for the determination of flurbiprofen in cataplasm.

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 1m 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.

Physicochemical Properties and Transdermal Absorption of a Flurbiprofen and Lidocaine Complex in the Non-Crystalline Form

Amorphous drug formulations exploiting drug-drug interactions have been extensively studied. This study aims to develop a transdermal system containing an amorphous complex of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen (FLU) and lidocaine (LDC) for alleviating chronic pain. The high-viscosity complex between FLU and LDC (Complex) was obtained by heating in ethanol. For the complex, attenuated total reflection-Fourier transform infrared spectroscopy showed a shift in the carboxy-group-derived peak of FLU, and differential scanning calorimetry indicated the endothermic peaks associated with the melting of FLU and LDC disappeared. 13C dipolar decoupling and 15N cross-polarization magic-angle spinning nuclear magnetic resonance measurement suggested the interaction between the carboxyl group of FLU and the secondary amine of LDC. The interaction between the aromatic rings of FLU and LDC contributed to the molecular complex formation. The solubility of FLU from the complex was about 100 times greater than FLU alone. The skin permeation flux of FLU from the complex through the hairless mouse skin was 3.8 times higher than FLU alone in hypromellose gel. Thus, adding LDC to the formulation can be an effective method for enhancing the skin permeation of NSAIDs, which can prove useful for treating chronic pain and inflammatory diseases.

Topological effects in ultrafast photoinduced processes between flurbiprofen and tryptophan in linked dyads and within human serum albumin.

The interaction dynamics between flurbiprofen (FBP) and tryptophan (Trp) has been studied in covalently linked dyads and within human serum albumin (HSA) by means of fluorescence and ultrafast transient absorption spectroscopy. The dyads have proven to be excellent models to investigate photoinduced processes such as energy and/or electron transfer that may occur in proteins and other biological media. Since the relative spatial arrangement of the interacting units may affect the yield and kinetics of the photoinduced processes, two spacers consisting of amino and carboxylic groups separated by a cyclic or a long linear hydrocarbon chain (1 and 2, respectively) have been used to link the (S)- or (R)-FBP with the (S)-Trp moieties. The main feature observed in the dyads was a strong intramolecular quenching of the fluorescence, which was more important for the (S,S)- than for the (R,S)- diastereomer in dyads 1, whereas the reverse was true for dyads 2. This was consistent with the results obtained by simple molecular modelling (PM3). The observed stereodifferentiation in (S,S)-1 and (R,S)-1 arises from the deactivation of 1Trp*, while in (S,S)-2 and (R,S)-2 it is associated with 1FBP*. The mechanistic nature of 1FBP* quenching is ascribed to energy transfer, while for 1Trp* it is attributed to electron transfer and/or exciplex formation. These results are consistent with those obtained by ultrafast transient absorption spectroscopy, where 1FBP* was detected as a band with a maximum at ca. 425 nm and a shoulder at ∼375 nm, whereas Trp did not give rise to any noticeable transient. Interestingly, similar photoprocesses were observed in the dyads and in the supramolecular FBP@HSA complexes. Overall, these results may aid to gain a deeper understanding of the photoinduced processes occurring in protein-bound drugs, which may shed light on the mechanistic pathways involved in photobiological damage.

Impact of multiple H/D replacements on the physicochemical properties of flurbiprofen.

Although deuterium incorporation into pharmaceutical drugs is an attractive way to expand drug modalities, their physicochemical properties have not been sufficiently examined. This study focuses on examining the changes in physicochemical properties between flurbiprofen (FP) and flurbiprofen-d8 (FP-d8), which was successfully prepared by direct and multiple H/D exchange reactions at the eight aromatic C-H bonds of FP. Although the effect of deuterium incorporation was not observed between the crystal structures of FP and FP-d8, the melting point and heat of fusion of FP-d8 were lower than those of FP. Additionally, the solubility of FP-d8 increased by 2-fold compared to that of FP. Calculation of the interaction energy between FP/FP-d8 and water molecules using the multi-component density functional theory method resulted in increased solubility of FP-d8. These novel and valuable findings regarding the changes in physicochemical properties triggered by deuterium incorporation can contribute to the further development of deuterated drugs.

Cyclodextrin-based nanogel of flurbiprofen for dermal application: In vitro studies and in vivo skin irritation evaluation

The aim of this study was to develop and characterize flurbiprofen (FB)-loaded cyclodextrin (CD) based nanogel formulations for dermal application. Nanogels were produced via emulsification solvent evaporation and then incorporated into a hydroxypropyl methyl cellulose (HPMC) gel. The visual examination, pH, viscosity, dynamic rheological measurements and drug content analysis of nanogels were assessed. In vitro and ex vivo permeation, stability, and skin irritation were performed. pH of the FB-loaded nanogel and the nanogels in HPMC were 10.6 ± 0.1 and 7.5 ± 0.1 (neutral) respectively. The highest and lowest viscosities were observed in FB-loaded nanogels and in FB-free nanogels in HPMC, respectively. The tangent δ and storage modulus values of FB-loaded nanogel in HPMC were higher than those of FB-loaded nanogel. FB from nanogels in HPMC was 100% by 48 h. The final nanogel formulation was physically and chemically stable over 12 months. Skin irritation test showed no skin irritation or cellular infiltration on the histological level. In vitro and ex vivo permeation showed that the nanogels could be effective and stable formulations, especially in the dermal application of a hydrophobic molecule.

Mechanistic insights of different release behaviors dominated by drug physicochemical properties in polyisobutylene pressure sensitive adhesive

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.

Construction and Evaluation of Hyaluronic Acid-Coated Flurbiprofen-Layered Double Hydroxide Ocular Drug Delivery System.

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 cornealresidencetime 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 24h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8nm, the potential was 42.2 ± 1.2mV, 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 200-400kDa and the concentration of HA solution was 1.25mg·mL -1, the final particle size of HA-FB-LDH was 185.8 ± 3.3nm, and potential of - 31.4 ± 0.7mV. 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 12h 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.

Mechanistic Study of Release Characteristics of Two Active Ingredients in Transdermal Patch Containing Lidocaine-Flurbiprofen Ionic Liquid.

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.

NMR Investigation of the Interaction of Three Non-Steroidal Anti-Inflammatory Drugs with Human Serum Albumin.

The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to-protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction.

Preparation and evaluation of oral soft chewable jelly containing flurbiprofen.

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.