Ketoprofen Research Articles

Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting

This work developed high drug-load pellets for colon targeting in minimal steps by coupling hot-melt extrusion (HME) with a die-surface cutting pelletizer, offering a potential continuous pellet manufacturing process. Ketoprofen (KTP) was selected as a model drug for this study due to its thermal stability and severe upper gastrointestinal side effects. Low and high methoxyl grade pectins were the enzyme-triggered release matrix, and hydroxypropyl methylcellulose (HME 4 M/HME 100LV) was used as a premature release-retarding agent. The powder X-ray diffraction technique and the differential scanning calorimetry results revealed that KTP exists in the solid-solution state within the polymeric matrix after the HME step. The scanning electron micrographs of the fabricated pellets showed a smooth surface without any cracks. The lead formulation showed the lowest premature drug release (∼13%) with an extended KTP release profile over a 24 h period in the presence and absence of the release-triggering enzyme. The lead formulation was stable for 3 months at accelerated stability conditions (40 °C/75 ± 5% RH) concerning drug content, in vitro release, and thermal characteristics. In summary, coupling HME and pelletization processes could be a promising technology for developing colon-targeted drug delivery systems.

HPLC Method Validation for the Estimation of Lignocaine HCl, Ketoprofen and Hydrocortisone: Greenness Analysis Using AGREE Score.

In the current study, the reversed-phased high-pressure liquid chromatography (RP-HPLC) method was proposed for the estimation of lignocaine hydrochloride (LIG), hydrocortisone (HYD) and Ketoprofen (KET) according to International Conference for Harmonization (ICH) Q2 R1 guidelines, in a gel formulation. The chromatographic evaluation was executed using Shimadzu RP-HPLC, equipped with a C8 column and detected using UV at 254 nm wavelength, using acetonitrile and buffer (50:50) as a mobile phase and diluent, at flow rate 1 mL/min and n injection volume of 20 μL. The retention time for LIG, HYD, and KET were 1.54, 2.57, and 5.78 min, correspondingly. The resultant values of analytical recovery demonstrate accuracy and precision of the method and was found specific in identification of the drugs from dosage form and marketed products. The limit of detection (LOD) for LIG, HYD, and KET were calculated to be 0.563, 0.611, and 0.669 ppm, while the limit of quantification (LOQ) was estimated almost at 1.690, 1.833, and 0.223 ppm, respectively. The AGREE software was utilized to evaluate the greenness score of the proposed method, and it was found greener in score (0.76). This study concluded that the proposed method was simple, accurate, precise, robust, economical, reproducible, and suitable for the estimation of drugs in transdermal gels.

Constructed wetlands for the treatment of household organic micropollutants with contrasting degradation behaviour: Partially-saturated systems as a performance all-rounder

The degradability of specific organic micropollutants in constructed wetlands (CWs) may differ depending on the prevalence of oxic or anoxic conditions. These conditions are governed, among other factors, by the water saturation level in the system. This study investigated the removal of three environmentally-relevant organic micropollutants: bisphenol-group plasticizer bisphenol S (BPS), household-use insecticide fipronil (FPN) and non-steroidal anti-inflammatory drug ketoprofen (KTP) in the model CWs set up in an outdoor column system. BPS and KTP, in contrast to FPN, exhibit higher biodegradability potential under oxic conditions. The experimental CWs were operated under various saturation conditions: unsaturated, partially saturated and saturated, and mimicked the conditions occurring in unsaturated, partially-saturated intermittent vertical-flow CWs and in horizontal-flow CWs, respectively. The CWs were fed with synthetic household wastewater with the concentration of the micropollutants at the level of 30–45 μg/L. BPS and KTP exhibited contrasting behaviour against FPN in the CWs in the present experiment. Namely, BPS and KTP were almost completely removed in the unsaturated CWs without a considerable effect of plants, but their removal in saturated CWs was only moderate (approx. 50%). The plants had only a pronounced effect on the removal of BPS in saturated systems, in which they enhanced the removal by 46%. The removal of FPN (approx. 90%) was the highest in the saturated and partially-saturated CWs, with moderate removal (66.7%) in unsaturated systems. Noteworthy, partially-saturated CWs provided high or very high removal of all three studied substances despite their contrasting degradability under saturated and unsaturated conditions. Namely, their removal efficiencies in planted CWs were 95.9%, 94.5% and 81.6%, for BPS, KTP and FPN, respectively. The removal of the micropollutants in partially-saturated CWs was comparable or only slightly lower than in the best treatment option making it the performance all-rounder for the compounds with contrasting biodegradability properties.

Optimized L-SNEDDS and spray-dried S-SNEDDS using a linked QbD-DM3 rational design for model compound ketoprofen

A QbD-DM3 strategy was used to design ketoprofen (KTF) optimized liquid (L-SNEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS). Principal component analysis was used to identify the optimized L-SNEDDS containing Capmul® MCM NF, 10 % w/w; Kolliphor® ELP, 60 % w/w; and propylene glycol, 30 % w/w. The S-SNEDDS was manufactured by spray-drying a feed dispersion prepared by dissolving the optimized KTF-loaded L-SNEDDS in an ethanol-Aerosil® 200 dispersion. A Box Behnken design was employed to evaluate the effect of drug concentration (DC), Aerosil® 200 concentration (AC) and feed rate (FR) on maximizing percent yield (PY) and loading efficiency (LE). The optimal levels of DC, AC, and FR were 19.9 % w/w, 30.0 % w/w, and 15.0 %, respectively. The optimized S-SNEDDS was amorphous, and its dissolution showed a 2.37-fold increase in drug release compared to KTF in 0.1 HCl. An optimized independent spray-dried S-SNEDDS verification batch showed that the predicted and observed PY and LE were 70.49 % and 92.49 %, and 70.02 % and 91.27 %, respectively. The optimized L-SNEDDS and S-SNEDDS also met their quality target product profile criteria for globule size <100 nm, polydispersity index < 0.400, emulsification time < 30 s, and KTF L-SNEDDS solubility 100-fold greater than its water solubility.

Y-Site Compatibility Studies of Ketoprofen with Parenteral Nutrition Admixtures for Central and Peripheral Administration.

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.

Low-cost agricultural wastes (orange peels) for the synthesis and characterization of activated carbon biosorbents in the removal of pharmaceuticals in multi-component mixtures from aqueous matrices

In recent years, bio-based carbons derived from environmentally friendly biomass materials have received considerable attention because of their abundance, easy processability, tunable surface properties and relatively low cost. Herein, a simple, less hazardous and low-cost method for the synthesis of ultrahigh surface area activated carbon material was proposed using orange peels as a carbon source. Within this context, three different biosorbents were synthesized: activated carbon samples derived from orange peels after activation with (i) phosphoric acid by pyrolysis at 450 °C (ORPs-H3PO4(450)) and (ii) at 650 °C (ORPs-H3PO4(650)), as well as (iii) after activation with potassium hydroxide at 450 °C (ORPs-KOH(450)). Characterisation and morphology of all materials has been conducted using various characterization techniques as FTIR, BET and SEM. The adsorption capacity was evaluated in a multi-component fashion for a mixture of five NSAIDs, namely diclofenac (DCF), ibuprofen (IBF), ketoprofen (KPF), salicylic acid (SAL) and paracetamol (PAR). The evaluation of the adsorption was achieved by investigating several variables like the effect of the solution’s pH, of contact time (kinetic modelling) and of the initial pharmaceuticals’ concentration. Acidic pH (pH = 2) appeared to be the optimal pH value while the pseudo-second order kinetic model and the Langmuir model demonstrate better fitting to the adsorption kinetics and isotherms respectively. Increase of temperature from 25 to 35 °C appears to have a positive effect on the adsorption capacity and the negative values of ΔG0 indicated that all target pharmaceuticals were adsorbed spontaneously to the synthesized biosorbents. Aqueous eluents with different pH values were used to accomplish desorption while pH = 6 appears to the optimum pH value for the desorption of the target pollutants.

Computer-aided analysis for identification of novel analogues of ketoprofen based on molecular docking, ADMET, drug-likeness and DFT studies for the treatment of inflammation

Computer-based drug design is increasingly used in strategies for discovering new molecules for therapeutic purposes. The targeted drug is ketoprofen (KTP), which belongs to the family of non-steroidal anti-inflammatory drugs, which are widely used for the treatment of pain, fever, inflammation and certain types of cancers. In an attempt to rationalize the search for 72 new potential anti-inflammatory compounds on the COX-2 enzyme, we carried out an in silico protocol that successfully combines molecular docking towards COX-2 receptor (5F1A), ADMET pharmacokinetic parameters, drug-likeness rules and molecular electrostatic potential (MEP). It was found that six of the compounds analyzed satisfy with the associated values to physico-chemical properties as key evaluation parameters for the drug-likeness and demonstrate a hydrophobic character which makes their solubility in aqueous media difficult and easy in lipids. All the compounds presented good ADMET profile and they showed an interaction with the amino acids responsible for anti-inflammatory activity of the COX-2 isoenzyme. The calculation of the MEP of the six analogues reveals new preferential sites involving the formation of new bonds. Consequently, this result allowed us to understand the origin of the potential increase in the anti-inflammatory activity of the candidates. Finally, it was obtained that six compounds have a binding mode, binding energy, and stability in the active site of COX-2 like the reference drug ketoprofen, suggesting that these compounds could become a powerful candidate in the inhibition of the COX-2 enzyme. Communicated by Ramaswamy H. Sarma

Adsorption of paracetamol and ketoprofenon activated charcoal prepared from the residue of the fruit of Butiacapitate: Experiments and theoretical interpretations

This paper describes the removal process via adsorption of paracetamol (PRC) and ketoprofen (KTP) on activated charcoal prepared from the residue of the fruit of Butiacapitate. Some adsorbent characterizations are carried out for a plausible analysis of the adsorption results and for the description of adsorption mechanism. Modelling investigations show that the double layer derived from statistical physiscs can be adopted to interpret the adsorption data. Interestingly, the adsorption mechanism can be elucidated via the model parameters determined at different temperatures. The performance of the adsorbent in terms of maximum adsorption capacity increased from 101.16 to 134.52 mg/g for KTP molecules and decreased from 98.19 to 73 mg/g for PRC molecules, by increasing the temperature, which are in line with the experimental values retrieved. These tendencies of adsorption capacities may be related to the behavior of the number of PRC and KTP pharmaceuticals captured per functional group of the adsorbent. Overall, the modeling results show also that the values of adsorption energies associated to the two layers of KTP and PRC molecules on the adsorbent surface are lower than 40 kJ/mol, implying that only physical type interactions occur in the removal process of these pharmaceutical molecules.

Efficient Multi‐walled Carbon Nanotubes/Iron Oxide Nanocomposite for the Removal of the Drug Ketoprofen for Wastewater Treatment Applications

AbstractCurrent environmental restrictions, such as the zero liquid discharge policy, require developing new methods to completely remove micropollutants from wastewater. Non‐steroidal anti‐inflammatory drugs (NSAID) are major component of such pollutants. The adsorptive removal of ketoprofen (KP), a widely prescribed NSAID, was studied using a newly synthesized magnetic adsorbent. The maximum adsorption capacity was determined to be 39.2 mg/g with almost 98 % removal for 50 mg/L KP at neutral pH. The adsorption of KP was found to be pH dependent and more efficient in acidic media. The isothermal behavior of the adsorbent followed a sigmoidal behavior and was best fitted to the corresponding‐states equation (CSE). The adsorption was found to follow second‐order kinetics with a half‐life of 4.4 min. The adsorption was also found to be exothermic and therefore it is favorable at low temperatures. The study also showed that the adsorbent can be regenerated for several adsorption‐desorption cycles. The adsorption mechanism was also explored by state‐of‐the‐art periodic quantum theoretical calculations.

A Comprehensive Review for Removal of Non-Steroidal Anti-Inflammatory Drugs Attained from Wastewater Observations Using Carbon-Based Anodic Oxidation Process.

Non-steroidal anti-inflammatory drugs (NSAIDs) (concentration <µg/L) are globally acknowledged as hazardous emerging pollutants that pass via various routes in the environment and ultimately enter aquatic food chains. In this context, the article reviews the occurrence, transport, fate, and electrochemical removal of some selected NSAIDs (diclofenac (DIC), ketoprofen (KTP), ibuprofen (IBU), and naproxen (NPX)) using carbon-based anodes in the aquatic environment. However, no specific protocol has been developed to date, and various approaches have been adopted for the sampling and elimination processes of NSAIDs from wastewater samples. The mean concentration of selected NSAIDs from different countries varies considerably, ranging between 3992–27,061 µg/L (influent wastewater) and 1208–7943 µg/L (effluent wastewater). An assessment of NSAIDs removal efficiency across different treatment stages in various wastewater treatment plants (WWTPs) has been performed. Overall, NSAIDs removal efficiency in wastewater treatment plants has been reported to be around 4–89%, 8–100%, 16–100%, and 17–98% for DIC, KTP, NPX, and IBU, respectively. A microbiological reactor (MBR) has been proclaimed to be the most reliable treatment technique for NSAIDs removal (complete removal). Chlorination (81–95%) followed by conventional mechanical biological treatment (CMBT) (94–98%) treatment has been demonstrated to be the most efficient in removing NSAIDs. Further, the present review explains that the electrochemical oxidation process is an alternative process for the treatment of NSAIDs using a carbon-based anode. Different carbon-based carbon anodes have been searched for electrochemical removal of selected NSAIDs. However, boron-doped diamond and graphite have presented reliable applications for the complete removal of NSAIDs from wastewater samples or their aqueous solution.

A magnetically separable α-NiMoO4/ZnFe2O4/coffee biochar heterojunction photocatalyst for efficient ketoprofen degradation

In this study, a novel heterostructure i.e., ZnFe2O4 nanosphere-decorated α-NiMoO4 nanorods on coffee biochar (BC), was fabricated via a hydrothermal method. The magnetically separable α-NiMoO4/ZnFe2O4/BC composite demonstrated 98.65 % degradation of ketoprofen (KP) in 180 min under visible light irradiation. Analysis of cyclic tests, total organic carbon, and fluorescence excitation-emission matrices revealed the excellent stability and mineralization abilities of photocatalysts, respectively. The effects of influencing factors (pH, anions, and different concentrations of KP/photocatalysts) on degradation of KP by the photocatalysts were suggested as promising prospects in water/wastewater treatment. BC acts as a conductor and an electron mediator in heterostructure. The enhanced photocatalytic performance of the heterostructure was ascribed to increased visible light absorption and efficient photoinduced charge carrier separation. Furthermore, photoluminescence spectral and electrochemical investigations indicated the efficient separation of photoinduced charge carriers. Electron spin resonance spectroscopy and scavenger experiments demonstrated that •OH played a major role in KP degradation. According to the liquid chromatography-tandem mass spectroscopy analysis, KP was degraded via three degradation pathways by 24 degraded intermediates. This study provides a new perspective on fabrication of efficient heterojunction photocatalysts exhibiting good recovery and insight on mechanisms and pathways underlying KP degradation.

Computer-aided design-based green fabrication of magnetic molecularly imprinted nanoparticles for specific extraction of non-steroidal anti-inflammatory drugs

Novel magnetic molecularly imprinted nanoparticles (MMINs) were greenly synthesized by one-pot method with ketoprofen (KP) as template molecule and used as the adsorbent of magnetic solid-phase extraction (MSPE) for selective extraction of non-steroidal anti-inflammatory drugs (NSAIDs). By means of calculation simulation technology, N-vinyl pyrrolidone (NVP) and allylglycine (AG) were rapidly screened as suitable dual functional monomers. After that, self-assembly solution of KP-NVP/AG, magnetic source (Fe3+/Fe2+) and N,N-dimethylformamide were mixed in one pot, and then simple hydrothermal technology was utilized to quickly prepare MMINs with a total reaction period of 3.5 h. A series of characterized techniques were adopted to study the structure, morphology and magnetic property of prepared MMINs. Results indicated that the adsorption behavior of MMINs towards KP was well fit for Freundlich adsorption model and pseudo-second-order kinetics. Under the optimal conditions, the obtained MMINs exhibited satisfactory specific recognition capability. The imprinting factor and extraction capacity towards KP were as high as 6.73 and 15.6 mg/g, respectively. Combining with HPLC, accurate and reliable approach for the measurement of trace NSAIDs in environmental waters and human urine samples was developed. The established approach exhibited low limits of detection (0.0024–0.0029 and 0.0026–0.0045 μg/L for water and urine samples, respectively), good fortified recoveries (77.8–119 % for water samples and 78.3–120 % for urine samples) and satisfactory precision (RSDs ≤ 9.7 %).

Risk assessment for uptake and accumulation of pharmaceuticals by baby leaf lettuce irrigated with reclaimed water under commercial agricultural activities

The use of reclaimed water to irrigate agricultural crops has increased in recent years as a consequence of water shortage constituting a potential risk for human health. The main objective of this study was to evaluate the impact on the soil-plant system and determining the accumulation of carbamazepine (CBZ), diclofenac (DCF), ketoprofen (KTP) and naproxen (NPX) in the edible part of lettuce under commonly used agricultural practices in commercial production. For this purpose, red oak baby lettuce (Lactuca sativa L.) was irrigated with reclaimed water fortified with different concentrations of pharmaceuticals. The study was carried out in two different scenarios: soil and tray. The tray experiments were conducted with substrate and took place at three different seasons of the year. Lettuce tissue sampled from these experiments were analysed 3 times during the lettuce growing cycle (first, second and third harvest). The practices of first harvest regrowth were also evaluated. For all experiments, CBZ showed the highest accumulation in lettuce leaves of the pharmaceuticals tested, showing a correlation between irrigation exposure time and pharmaceutical uptake. Unexpectedly, DCF was the compound with the highest uptake levels after regrowth practices. Results suggested that pharmaceuticals uptake could be directly associated with the irrigation method and possible accumulation in soil and substrates, while concentration of pharmaceuticals in substrates were 10 times higher. Based on the concentration values detected in lettuce leaves, the risk assessment suggests that no compounds imply any risk to human health, except CBZ for those on vegetarian diets in the tray scenario. Although commercial agricultural practices are usually not considered with regards to risk reduction, in this experiment we demonstrated that climatic conditions are a key factor in pharmaceuticals uptake and different agricultural practices (soil cropping and drip irrigation) can limit the presence of pharmaceutical compounds in crops.

The Potential of Constructed Wetland Systems and Photodegradation Processes for the Removal of Emerging Contaminants—A Review

The presence of emerging organic contaminants (EOCs) in the environment is increasing and requires the development of technologies for their effective removal. Therefore, a literature review on the behavior of EOCs during municipal wastewater treatment, both in major treatment systems and particularly in constructed wetlands (CWs), was carried out. The study also reviewed the behavior of EOCs in anaerobic digesters (ADs) and advanced oxidation processes, particularly in TiO2-based photocatalysis, which are being proposed as promising pre- and post-treatments for combination with CW. The following ten compounds were screened: acetaminophen (ACE), ofloxacin (OFL), caffeine (CAF), carbamazepine (CBZ), ketoprofen (KET), ibuprofen (IBU), diclofenac (DCL), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). The degradation pathways of the selected EOCs are largely influenced by their physicochemical and biochemical properties. Sorption and biodegradation are the main elimination mechanisms found in AD and CW treatment systems, where the combination of anaerobic and aerobic environments improves the elimination efficiency of EOCs. However, various contaminants appear recalcitrant. In this sense, in combination with CWs, TiO2-based photocatalysis emerges as a promising post-treatment for advanced EOC removal from wastewater.

Rapid determination of NSAIDs by capillary and microchip electrophoresis with capacitively coupled contactless conductivity detection in wastewater.

A simple, rapid method using CE and microchip electrophoresis with C4 D has been developed for the separation of four nonsteroidal anti-inflammatory drugs (NSAIDs) in the environmental sample. The investigated compounds were ibuprofen (IB), ketoprofen (KET), acetylsalicylic acid (ASA), and diclofenac sodium (DIC). In the present study, we applied for the first time microchip electrophoresis with C4 D detection to the separation and detection of ASA, IB, DIC, and KET in the wastewater matrix. Under optimum conditions, the four NSAIDs compounds could be well separated in less than 1min in a BGE composed of 20mM His/15mM Tris, pH 8.6, 2mM hydroxypropyl-beta-cyclodextrin, and 10% methanol (v/v) at a separation voltage of 1000-1200V. The proposed method showed excellent repeatability, good sensitivity (LODs ranging between 0.156 and 0.6mg/L), low cost, high sample throughputs,portable instrumentation for mobile deployment, and extremely lower reagent and sample consumption. The developed method was applied to the analysis of pharmaceuticals in wastewater samples with satisfactory recoveries ranging from 62.5% to 118%.

Unusual Correlation between the Apparent Amorphous Solubility of a Drug and Solubilizer Concentration Revealed by NMR Analysis.

Herein, we investigated the effect of the solubilizers, cetyltrimethylammonium bromide (CTAB) and amino methacrylate copolymer (Eudragit E PO, EUD-E), on the apparent amorphous solubility of ketoprofen (KTP) and free KTP concentrations in an aqueous phase when a KTP-rich phase was generated by liquid-liquid phase separation. Quantitative analysis by solution nuclear magnetic resonance (NMR) revealed that the apparent amorphous solubility of KTP increased with increasing EUD-E concentrations by the solubilization of KTP into the EUD-E micelles; this was reminiscent of the improvement in the apparent crystalline solubility of KTP observed when EUD-E was added. In contrast, the apparent amorphous solubility of KTP decreased with increasing CTAB concentrations, although the solubilizing ability of CTAB was stronger than that of EUD-E when the KTP-rich phase was absent. NMR analysis revealed that CTAB was distributed into the KTP-rich phase to a relatively large extent. This resulted in a significant reduction of the chemical potential of KTP in the KTP-rich phase in the CTAB solution. Thus, the maximum free KTP concentration in the aqueous phase was reduced more significantly in the CTAB solution than in the EUD-E solution. Moreover, the solubilization effect of KTP by the CTAB micelles in the aqueous phase was drastically diminished due to the distribution of CTAB into the KTP-rich phase. As a result, the apparent amorphous solubility of KTP reached a minimum at a CTAB concentration of 200 μg/mL. A further increase in the CTAB concentration resulted in an improvement in the apparent amorphous solubility of KTP due to the solubilization effect of CTAB remaining in the aqueous phase. The present study highlights the impact of solubilizer selection on the apparent amorphous solubility and attainable supersaturation of the drug, which should be considered during the development of supersaturating formulations to obtain preferable oral absorption.

Removal of nonsteroidal anti-inflammatory drugs and analgesics from wastewater by adsorption on cross-linked β-cyclodextrin

We present a method using the material in the form of cross-linked β-cyclodextrin (CD) showing high efficiency in the simultaneous removal of hazardous pollutants from sewage, such as diclofenac (DIC), ibuprofen (IBU), ketoprofen (KETO), naproxen (NAPR), salicylic acid (SALI) and tramadol (TRAM). The material is stable and particularly easy to regenerate. The sorbent probably remembers the shape of the contaminants, which increases its sorption capacity after the second use. The kinetics of the KETO adsorption process from one-, two- and three-component solutions are well described by the pseudo-second-order model. The maximum polymer capacity was 162.60 mg g−1. The interactions of KETO with CD were investigated, indicating that the main sorption mechanism is based on supramolecular interaction and uptake by a polymer network. The material is not sensitive to low pH and high salinity, so it can be used for the treatment of DIC, IBU, and KETO post-production wastewaters.

Enhancement of the Transdermal Delivery of Nonsteroidal Anti-inflammatory Drugs Using Liposomes Containing Cationic Surfactants

New hybrid liposomes based on cationic amphiphiles with different structures of the head group (cetyltrimethylammonium bromide (CTAB), 3-hexadecyl-1-hydroxyethylimidazolium bromide (IA-16(OH)), 1-(butylcarbamoyl)oxyethyl-3-hexadecylimidazolium bromide (IAC 16(Bu)), and hexadecylmethylpyrrolidinium bromide (PR-16)) were developed for transdermal administration of nonsteroidal anti-inflammatory drugs. The different surfactant/lipid compositions were studied to obtain stable liposomes with high functionality. The hydrodynamic diameter of cationic liposomes was ∼110 nm. An admixture of cationic surfactants and PC liposomes improves the physicochemical properties of vesicles and transdermal diffusion rate and prolongs the release of drugs. Liposomal diclofenac sodium (DS) and ketoprofen (KP) were tested (using Franz cells) for transdermal penetration. Drug diffusion monitoring for 48 h demonstrated that the maximum DS and KP penetration through the synthetic membranes (Strat-M) is characterized by values of 255 ± 2 and 186 ± 3 μg/cm2, respectively. The influence of the surfactant head group on the properties (stability, release profile, permeability) of cationic liposomes was shown for the first time. While the drug specificity is evident for the rate of release, the permeability increases as follows: conventional liposomes < CTAB/PC < PR-16/PC < IAC-16(Bu)/PC < IA-16(OH)/PC for both medicines. The rat paw edema model was used to assess the anti-inflammatory effect of the IA-16(OH)/PC leader formulation in vivo. It was found that liposomal DS and KP are effective for relieving rat paw edema. It should be noted that DS-loaded hybrid liposomes demonstrated the highest therapeutic efficacy compared to conventional vesicles.

Solid phase-fabrication of magnetically separable Fe3O4@graphene nanoplatelets nanocomposite for efficient removal of NSAIDs from wastewater. Perception of adsorption kinetics, thermodynamics, and extra-thermodynamics

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most detected pharmaceuticals in wastewater and likely pass to drinking water. Magnetic nanocomposite has been greenly fabricated for removal of different NSAIDs; ibuprofen (IP), ketoprofen (KP), naproxen (NX), and diclofenac sodium salt (DF); from wastewater. Solid-phase fabrication of the magnetically separable nanocomposite has been optimized using iron oxide (Fe3O4) and graphene nanoplatelets (GNP) precursors. The characterization showed the homogenous distribution of the magnetite over the GNP with a high specific surface area. Different parameters having a potential influence on the removal of the NSAIDs from wastewater by the Fe3O4@GNP nanocomposite were studied and optimized for efficient performance that achieves adsorption capacities of 8.76, 10.6, 14.3, and 7.63 mg/g for KP, NX, DF, and IP, respectively (296 K). The adsorption of the four NSAIDs by the Fe3O4@GNP nanocomposite followed pseudo-second-order kinetics, and it is mainly controlled by the intraparticle diffusion process. The thermodynamic and extra-thermodynamic studies demonstrated that the adsorption is endothermic and is affected by enthalpy-entropy compensation. The molecular interactions of the four drugs with the nanocomposite have been explored. Successful application of the nanocomposite for fast and efficient removal of the NSAIDs from wastewater has been accomplished with an average removal of 71.0%.

Adsorption of nonsteroidal anti-inflammatory drugs onto composite beads of a 1D flexible framework MIL-53(Al): Adsorption mechanisms and fixed-bed study

The adsorption mechanisms of three nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen (IBP), ketoprofen (KET), and naproxen (NPX), applied onto a pristine 1D flexible framework MIL-53(Al) were compared with those adsorbed on MIL-53(Al)/alginate (AM) and polyvinylidene fluoride/MIL-53(Al) (PM) composite beads through investigation of single-solute batch and fixed-bed systems. The 1D flexible framework of pristine MIL-53(Al) exhibited outstanding adsorption capacities for the three NSAIDs (IBP > NPX > KET) in comparison to powdered activated carbon via an increase in pore diffusion through the 1D framework supported by the breathing effect phenomena. The MIL-53(Al)/alginate at 3:25 w/w (AM25) exhibited better adsorption capacities for the three NSAIDs than the composite beads with higher MIL-53(Al) ratios (3:50 and 3:75 w/w). However, the adsorption of the three NSAIDs on AM25 was 2.2–5.5-times lower than that of the pristine MIL-53(Al). The dominant interactions of IBP between MIL-53(Al) were hydrogen bonding between the Al–OH(OH2) node of MIL-53(Al), the carboxylic groups of IBP, and the carboxylic group of terephthalic acid of MIL-53(Al). AM25 exhibited high selectivity for IBP against the background matrix of wastewater obtained from a hospital, and it could be applied at a low concentration range (μg/L). An increase in the empty bed contact time (38.7 min to 96.9 min) of fixed-bed systems for the adsorption of IBP on AM25 could improve the usage rate and fractional bed utilization; moreover, the breakthrough removal percentage was increased up to 98.1%. The multi-layer log-Thomas model can be fitted well for all breakthrough curves.