A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-κB pathway, Klotho, and miR-499a.

The majority of conventional osteoarthritis (OA) treatments are based on molecular adjustment of certain signaling pathways associated with osteoarthritis (OA) pathogenesis, however there is a significant need to search for more effective and safe treatments. This study centers around formulating Aceclofenac (ACF) with high bioavailability in combination with Citronellol oil and collagen. The optimal concentrations of Citronellol oil/D-Limonene oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were studied for thermophysical stability. Thermodynamically stable formula were analyzed for droplet size, zeta potential, and in-vitro permeation. Then, collagen based nanoemulsion were prepared to capitalize on its efficacy in reducing osteoarthritis side effects and characterized for nano size properties. Formulae F10 and F10C were chosen as optimum nanosize formula. Hense, they were prepared and characterized as nanoemulgel dosage form. The nanoemulgel formulae F10NEG1 and F10CNEG1 showed reasonable viscosity and spreadability, with complete drug release after 4 h. These formulae were chosen for further In vivo anti-OA study. Collagen based ACF/citronellol emugel were able to modulate HMGB-1/RAGE/NF-κB pathway, mitigating the production of inflammatory cytokine TNF-α. They were also able to modulate Klotho and miR-499, reducing serum CTXII and COMP, by reducing the cartilage destruction. Histological investigations validated the efficacy, safety, and superiority of Aceclofenac in combination with Citronellol oil and collagen (F10CNEG1) over solo the treated group (F10NEG1 and blank). Hence, the findings of the current work encourage the use of this promising combined formula in treatment of OA patients.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Delivery of nano-emulgel carrier: optimization, evaluation and in vivo anti-inflammation estimations for osteoarthritis.

Aim: Optimization and evaluation of Aceclofenac nanoemulgel for treatment for rheumatoid arthritis and reduction of GI irritation and enhancement of bioavaibility. Materials & methods: Different batches of emulgel and selected batch was proceeded for characterization like particle size, scanning electron microscopy, drug ingredient, in vitro release, Fourier transform infrared and x-ray diffraction in vitro inflammation and gel evaluation such as (spreadability, swelling index), ex vitro permeation, skin irritation and in vivo anti-inflammatory. Result: Emulgel showed nanometri size sustained release (79.96% in 6 h), compatibility and anti-inflammatory activity compared with pure drug. Concluded that emulgels had better (nearly twice as good) anti-inflammatory action as the commercial product. Conclusion: Compared with the commercial gel, the emulgel's anti-inflammatory effect had a quicker onset and a longer duration of action.

A non-steroidal anti-inflammatory drug (NSAID) aceclofenac is used as the treatment for rheumatoid arthritis. It is generally taken orally. However, there are a few issues with it being taken this way. The main ones are: some of the drug reacts too early in the body, meaning only a small amount of it reaches the parts of the body where it is needed; it can irritate the digestive system; and it does not dissolve very well in water, which also makes it harder to reach the parts of the body where it is needed. The authors of this study created a new type of gel for people to rub into their skin, instead of taking a pill. They hoped that this would allow the drug to be absorbed more directly into the parts of the body where it was needed, without irritating the digestive system. They tested the gel to see how well it contained and released the drug, how well it absorbed into the skin, and whether it irritated the skin. They found that the gel contained and released the drug more effectively than similar gels which are already available and caused less irritation to the skin.

QbD-assisted optimisation of liposomes in chitosan gel for dermal delivery of aceclofenac as synergistic approach to combat pain and inflammation.

Aceclofenac (ACE) is a drug that was precisely devised to circumvent the shortcomings associated with diclofenac. However, ACE too corresponds to nonsteroidal anti-inflammatory drug (NSAID)-related adverse effects, but with a lower amplitude. The present investigation seeks to develop liposomes loaded with ACE adopting a central composite design (CCD) and formulate a chitosan-based hydrogel for synergistic anti-inflammatory efficacy and improved ACE dermal administration. On the basis of preliminary vesicle size, Poly Dispersity Index (PDI), and drug entrapment, the composition of lipid, cholesterol, and vitamin E TPGS were chosen as independent variables. The formulation composition met the specifications for an optimum liposomal formulation, with total lipid concentration (13.5% w/w), cholesterol concentration (10% w/w), and surfactant concentration (2% w/w). With particle size and PDI of 174.22 ± 5.46 nm and 0.285 ± 0.01 respectively, the optimised formulation achieved an entrapment effectiveness of 92.08 ± 3.56%. Based on the CCD design, the optimised formulation Acec-Lipo opt was chosen and was subsequently transformed to a chitosan-based gel formulation for in vitro drug release, penetration through the skin, in vivo analgesic therapeutic activity, and skin irritation testing. % age oedema inhibition was found to be greatest with the Acec-Lipo opt gel formulation, followed by Acec gel. These results reinforce the notion that the inclusion of chitosan resulted in a synergistic effect despite the same strength of the drug. The findings suggested that Acec-Lipo incorporated in chitosan gel for skin targeting might be an effective formulation for topical ACE administration in clinical subjects.

Water dynamics on the structural properties of some NSAID's with leucine in the picosecond region using time domain spectroscopy.

Concentration-dependent dielectric response for non-steroidal anti-inflammatory drugs (NSAIDs): Aceclofenac (ACF) and Diclofenac (DCF) in the aqueous leucine solution have been reported at different concentrations and temperatures (298.15 K to 283.15 K). The time domain reflectometry technique in the frequency region of 1 GHz to 30 GHz was used for the present study. Complex permittivity (ε*), static dielectric constant (ε), dielectric relaxation time (τ), dipole moment (µ) and Kirkwood correlation factor (g) have been calculated and discussed in terms of the molecular interaction of water and the used drugs. To give more insights into the structural dynamics of drug-induced amino acids, the study includes molar enthalpy of activation (ΔH), entropy of activation (ΔS), and free energy of activation (ΔF). The overall study concludes that the drug (DCF) having a potent inhibitor of cyclooxygenase found a higher static dielectric constant (ε0) than that of the drug (ACF) having more carbon (C), hydrogen (H), and oxygen (O) in the chain, which is more efficient in controlling pain.Communicated by Ramaswamy H. Sarma.

Eutectic phase transition during tablet manufacture: effect of melting point of eutectic forming drug.

The aim was to investigate eutectic transition during tableting and storage. Mixtures of lidocaine and series of NSAIDs with increasing melting point were used as model systems to guide formulators to scaleup eutectic forming materials gaining enhanced dissolution while avoiding deleterious physical changes. Physical mixtures of NSAIDs with lidocaine were prepared at eutectic forming ratio. These were directly compressed, dry co-ground before compression, or compressed after wet granulation. Dissolution of tablets was compared to corresponding dry co-ground mixture. Thermograms of direct compressed tablet were compared to co-ground mixture and pure compound. Stability of direct compressed tablets was assessed. Tableting initiated eutexia which enhanced dissolution of NSAIDs. Eutexia was associated with tablet softening in case of low melting point ketoprofen and aceclofenac. Wet granulation hastened eutexia developing unacceptable tablet in case ketoprofen and aceclofenac. Tablets prepared by direct compression of physical mixtures underwent gradual eutectic transition upon storage with the magnitude of eutectic transition reducing with increased melting point of NSAIDs. Ketoprofen was physically unstable but aceclofenac degraded chemically as well. Tenoxicam and meloxicam tablets were physically and chemically stable. Direct compression after physical mixing is the best tableting technique, but low melting point drugs should consider different strategy before compression.

Development and In vitro Evaluation of Aceclofenac Buccal Film.

AIM: This study aimed to formulate and characterize aceclofenac buccal film formulations made of different polymers and evaluate the effects of polymer type on buccal film properties. MATERIALS AND METHODS: Five polymer types, namely hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (SCMC), polyvinyl alcohol (PVA), Eudragit S100, and Eudragit SR100, were used to prepare aceclofenac buccal film formulation either separately or combined by solvent-casting method. These formulations were evaluated in terms of physical appearance, folding test, film weight and thickness, drug content, percentage of elongation, moisture uptake, water vapor permeability, and in vitro drug release. RESULTS: The addition of Eudragit polymer in most of the produced buccal films was unacceptable with low folding endurance. However, the dissolution profile of buccal films made from PVA and Eudragit SR100 provided a controlled drug release profile. CONCLUSION: Buccal films can be formulated using different polymers either individually or in combination to obtain the drug release profile required to achieve a desired treatment goal. Furthermore, the property of the buccal films depends on the type and concentration of the polymer used.

Aceclofenac/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line.

Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.

Optimization and Production of Aceclofenac-Loaded Microfiber Solid Dispersion by Centrifugal Spinning.

Aceclofenac-loaded polyvinylpyrrolidone fiber-based amorphous solid dispersion was produced successfully by centrifugal spinning. The solution concentration and rotational speed were optimized to produce the fiber-based drug carrier system, with a determined production rate of 12.7 g/h dry solid fibers. The obtained fibers were bead-free and smooth-surfaced with an average diameter of 7.5 ± 2.5 µm. Gas chromatographic determinations revealed that ethanol, as a residual solvent, was well below the regulatory limit of 0.5%. Differential scanning calorimetric investigation and infrared spectroscopic measurements were used to track the physicochemical changes that intervene during fiber formation in the solid state. The results revealed that the rapid evaporation of the solvent was accompanied by a probable crystalline to amorphous transition of the active substance during centrifugal spinning. In vitro dissolution studies revealed an instantaneous disintegration of the fibrous structure and a rapid release of the active substance, with the microfibrous webs greatly outperforming the crystalline active substance, especially in the early time-points. This implies that centrifugal spinning offers a viable scale-up production process to prepare drug-loaded fiber-based solid dispersions.

Acriflavine: an efficient green fluorescent probe for sensitive analysis of aceclofenac in pharmaceutical formulations.

Acriflavine is a multipurpose drug that shows antibacterial, antiviral, antimalarial, and antifungal activities. The remarkable native fluorescence of acriflavine is exploited in analytical chemistry field as an efficient probe for analysis of pharmaceutical and biological compounds. The fluorescent probe action of acriflavine is based on the remarkable fluorescence turning-off via formation of ion-pair complexes with acidic drugs at a specific pH. Herein, the acidic drug aceclofenac is analysed for the first time using acriflavine as a fluorescent probe. Aceclofenac can form an ion-pair complex with acriflavine at pH 8.5, and hence it partially turns off the fluorescence intensity of acriflavine over a concentration range of 1-20 µg/mL. The fluorescence quenching was monitored at 502 nm following an excitation at 265 or 451 nm. The reaction stoichiometry between acriflavine and aceclofenac was found to be 1:1 using limiting logarithmic method. The type of quenching was confirmed to be static using Stern-Volmer plot. The method showed low values of quantitation limit (0.89 µg/mL) and detection limit (0.29 µg/mL). Moreover, the method was linear (r = 0.9999), accurate, precise (RSD < 1.7%), robust, and specific. The proposed method was successfully employed to analyse aceclofenac in its dosage forms with high %recovery (98-101%). Additionally, GAPI and AGREE approaches were used to guarantee the suggested techniques' greenness, and the findings showed an excellent level of greenness.

The long-lasting effects of aceclofenac, a COX-2 inhibitor, in a Poly I:C-Induced maternal immune activation model of schizophrenia in rats.

It is well established that rats exposed to inflammation during pregnancy or the perinatal period have an increased chance of developing schizophrenia-like symptoms and behaviors, and people with schizophrenia also have raised levels of inflammatory markers. Therefore, there is evidence supporting the idea that anti-inflammatory drugs may have therapeutic benefits. Aceclofenac is a nonsteroidal anti-inflammatory drug that has anti-inflammatory properties and is used clinically to treat inflammatory and painful processes such as osteoarthritis and rheumatoid arthritis, making it a potential candidate for preventive or adjunctive therapy in schizophrenia. This study therefore examined the effect of aceclofenac in a maternal immune activation model of schizophrenia, in which polyinosinic-polycytidylic acid (Poly I:C) (8 mg/kg, i.p.) was administered to pregnant rat dams. Young female rat pups received daily aceclofenac (5, 10, and 20 mg/kg, i.p., n = 10) between postnatal day 56 and 76. The effects of aceclofenac were compared with assessment of behavioral tests and ELISA results. During the postnatal days (PNDs) 73-76, behavioral tests were conducted in rats, and on PND 76, ELISA tests were performed to examine the changes in Tumor necrosis factor alpha (TNF-α), Interleukin-1ß (IL-1ß), Brain-derived neurotrophic factor (BDNF), and nestin levels. Aceclofenac treatment reversed deficits in prepulse inhibition, novel object recognition, social interaction, and locomotor activity tests. In addition, aceclofenac administration decreased TNF-α and IL-1ß expression in the prefrontal cortex and hippocampus. In contrast, BDNF and nestin levels did not change significantly during treatment with aceclofenac. Taken together, these results suggest that aceclofenac may be an alternative therapeutic adjunctive strategy to improve the clinical expression of schizophrenia in the further studies.

Aceclofenac and methotrexate combination therapy could influence Th1/Th17 axis to modulate rheumatoid-arthritis-induced inflammation.

Rheumatoid arthritis (RA) is an inflammatory, autoimmune and connective-tissue arthropathy. The methotrexate (MTX) and aceclofenac (ACL) combination drug regimen is known to regulate the immunological pathways. Also, RA-elicited inflammation is decreased by the combination drug treatment. ACL and MTX combination treatment has been shown to regulate the signaling pathway controlled by NF-κB and FOXO1. The present manuscript reviews the importance of the combination drug regimen to treat and/or manage RA. The combination drug regimen could affect the Th1/Th17 axis to switch the balance toward the immunoregulatory (Th1) phenotype for establishing immune homeostasis. In conclusion, we propose the study of the immunological signaling pathways in experimental humanized RA mice.

White analytical chemistry-driven stability-indicating concomitant chromatographic estimation of thiocolchicoside and aceclofenac using response surface analysis and red, green, and blue model.

White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power, and economical efficiency. White analytical chemistry-driven stability indicating chromatographic method has been developed for the concomitant analysis of thiocolchicoside and aceclofenac. The proposed chromatographic method has been developed using a safe and environmental-friendly organic solvents for the concomitant stability study of thiocolchicoside and aceclofenac. The analytical risk assessment was carried out for the identification of high-risk analytical risk factors and analytical method performance attributes. The mixture design was applied for the design of experiments-based response surface modeling of high-risk analytical risk factors and analytical method performance attributes. The degradation products were isolated and characterized using infrared, nuclear magnetic resonance, and mass spectral data. The proposed method was compared for its validation efficiency, greenness power, and cost-efficiency with published chromatographic methods using the red, green, and blue models. The white score of the proposed and reported method was calculated by averaging the red, green, and blue scores of the methods. The proposed method was found to be robust, green, and economical for the concomitant stability study of thiocolchicoside and aceclofenac.

Effect of Andrographis paniculata extract and Andrographolide on the pharmacokinetics of Aceclofenac and Celecoxib in rats.

Background: In India, for the treatment of cold, fever and inflammation, people consume herbal remedies containing Andrographis paniculata Nees (APE) as main ingredient, along with NSAIDs. So the purpose of this study is to investigate the effect of APE and pure andrographolide (AN) on the pharmacokinetic of with aceclofenac (ACF) and celecoxib (CXB) after oral co-administration in wistar rats. After co-administration of APE (equivalent to 20 mg/kg of AN) and AN (20 mg/kg) with ACF (5 mg/kg) and CXB (5 mg/kg) in rats, orally, drug concentrations in plasma were determined using HPLC method. Non-compartment model was used to calculate pharmacokinetic parameters like Cmax, Tmax, t1/2, MRT, Vd, CL, and AUC. Results: Co-administration of ACF and CXB with APE and pure AN altered the systemic exposure level of each compound in vivo. The Cmax, Tmax, MRT of CXB were increased whereas Vd and Cl of CXB were decreased significantly after co-administration of CXB with APE. Whereas co-administration of CXB with AN significantly decreased Vd, CL, and MRT of CXB. The concentration of ACF was increased significantly in co-administered groups with pure AN and APE. The AUC0-∞, AUMC0-∞, MRT, Vd and t1/2 of ACF were also significantly decreased in co-administered groups, hence CL of ACF was increased significantly. Conclusion: This study concludes that APE and pure AN have effect on pharmacokinetic of CXB and ACF in rat. Not only patients but medical practitioners using Andrographis paniculata should have awareness regarding probable herb-drug interactions with ACF and CXB.

Development of a New Voltammetric Method for Aceclofenac Determination on Glassy Carbon Electrode Modified with Hierarchical Nanocomposite.

Aceclofenac (ACL) is an anti-inflammatory drug, which is taken by patients who mainly suffer from rheumatoid conditions. In this work, we propose a new voltammetric method that allows the determination of ACL in pharmaceutics, urine, and plasma. As a working electrode, a glassy carbon electrode (GCE) modified with carbon nanofibers, carbon nanotubes, and NiCo nanoparticles (eCNF/CNT/NiCo-GCE) was used. The mentioned sensors are characterized by good repeatability and sensitivity, and their process of preparation is simple, fast, and cost-effective. Instrumental and method parameters were optimized, and the influence of interferences was investigated. To validate the analytical performance of the method, calibration was conducted. Good linearity was obtained (0.05-1.4 µM, r = 0.998), as well as excellent limit of detection (LOD) and limit of quantification (LOQ) values (0.7 nM and 2.1 nM, respectively). Calculated recoveries that were in the range of 98%-105% indicate that this method is accurate and might be used in routine laboratory practice.

Exploitation of capsule system for colon targeted drug delivery of biopolymer-based microparticles: in vivo and in vitro applications.

The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 ± 0.21% to 82.83 ± 0.22% for AC.LPO and 52.64 ± 0.11% to 80.36 ± 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher anti-inflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.

Corrigendum: Nanostructured lipid carrier-mediated transdermal delivery of aceclofenac hydrogel present an effective therapeutic approach for inflammatory diseases.

[This corrects the article DOI: 10.3389/fphar.2021.713616.].

Pharmacokinetic Interactions Between Tegoprazan and Naproxen, Aceclofenac, and Celecoxib in Healthy Korean Male Subjects.

PURPOSE: Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression and may be used with NSAIDs to reduce gastrointestinal adverse effects. The aim of this study was to evaluate the pharmacokinetic interaction between tegoprazan and commonly used NSAIDS, namely, naproxen, aceclofenac, and celecoxib. METHODS: An open-label, 3-cohort, randomized, multiple-dose, 3-way crossover study was conducted in healthy male subjects. In cohort 1, tegoprazan (50-mg tablet, once daily) and naproxen (500-mg tablet, twice daily) were administered separately or concurrently for 7 days in each period. In cohort 2, tegoprazan and aceclofenac (100-mg tablet, twice daily) were administered separately or concurrently for 7 days in each period. In cohort 3, tegoprazan and celecoxib (200-mg capsule, twice daily) were administered separately or concurrently for 7 days in each period. Pharmacokinetic blood samples were collected up to 24 hours after the last dose. FINDINGS: Seventeen subjects from cohort 1, sixteen subjects from cohort 2, and thirteen subjects from cohort 3 were included in the pharmacokinetic analysis. In cohort 1, the geometric least squares mean ratios (90% CIs) for AUCτ (AUC profiles over the dosing interval) and Css,max (Cmax at steady state) were 1.01 (0.91-1.12) and 0.99 (0.83-1.17) for tegoprazan, and 1.00 (0.97-1.03) and 1.04 (0.99-1.09) for naproxen, respectively. The values in cohort 2 were 1.03 (0.93-1.13) and 0.94 (0.86-1.04) for tegoprazan, and 1.06 (1.00-1.12) and 1.31 (1.08-1.60) for aceclofenac. The values in cohort 3 were 1.01 (0.86-1.18) and 1.02 (0.87-1.19) for tegoprazan, and 1.08 (0.96-1.22) and 1.18 (0.97-1.43) for celecoxib. IMPLICATIONS: Changes in the maximum aceclofenac or celecoxib concentrations were detected after concurrent administration with tegoprazan, which were considered mainly due to the pharmacodynamic effect of tegoprazan. Because systemic drug exposure (shown as AUCτ) was unchanged after concurrent administration of any 3 NSAIDs with tegoprazan, the increase in aceclofenac or celecoxib Css,max when administered with tegoprazan would not be clinically significant in practice. CLINICALTRIALS: gov Identifier: NCT04639804.

PEGylated aceclofenac solid lipid microparticles homolipid-based solidified reverse micellar solutions for drug delivery.

Aceclofenac is a non-steroidal anti-inflammatory drug with poor aqueous solubility and a short half-life resulting in low bioavailability. Aceclofenac-loaded solid lipid microparticles based solidified reverse micellar solution (SLMs-SRMS) for oral drug delivery was investigated to improve the bioavailability and control drug release. Hot homogenization method was adopted to prepare the SLMs using a homolipid irvingia fat and Phospholipon® 90H with or without propylene glycol 6000 (PEGylation) in different ratios and characterized in vitro. The in vivo anti-inflammatory activity of the drug was determined on mice inflamed with carrageenan as phlogistic agent. Results showed that the morphology and particle sizes of the SLMs were spherical and smooth and ranged between 5.24 ± 0.01-97.44 ± 0.18 µm. EE % ranged between 67 - 81 %. A significant (p < 0.05) viscosity of 490 mPasec-1 was obtained. FTIR spectra indicated compatibility amongst the constituents. DSC showed a broad peak which depicted an imperfect matrix resulting in a deformation of crystal arrangement creating many spaces for drug entrapment. Delayed drug release was observed in almost all the formulations in SIF (pH, 6.8). Anti-inflammatory activity showed a significant inhibitory effect (p < 0.05, up to 90 %). Hence, the aceclofenac-loaded SLMs-SRMS showed desirable characteristics and could be used for controlled delivery of aceclofenac and thus alternative to conventional aceclofenac oral formulation.