Drug-drug pharmaceutical multicomponent materials (PMMs) offer a promising strategy to modulate the physicochemical properties of active pharmaceutical ingredients, while enabling synergistic effects and combination therapy. Here, we report the preparation and full characterization of a new family of oxicam-metformin (MTF) salts, involving the nonsteroidal anti-inflammatory drugs piroxicam (PRX), meloxicam (MLX), and tenoxicam (TNX). Structural and computational studies revealed the role of supramolecular synthons in directing the salt formation and highlighted the relationship between molecular packing and physicochemical properties. Stability analyses showed that these materials enhance MTF stability, while particularly protecting PRX from hydration. Importantly, incorporation of MTF increased the aqueous solubility of the oxicams, while salt formation moderated the excessive solubility of free MTF. Significant modifications in fluorescence behavior were also observed, arising from interactions between functional groups involved in the fluorescence procedure within the frameworks. Overall, this study broadens the structural and functional landscape of oxicam-MTF salts and provides a rational framework for designing solid forms with improved stability and solubility.

Background: Osteoarthritis, a degenerative joint disorder, is characterized by synovial inflammation, cartilage degradation, and elevated proinflammatory mediators including interleukin-6 (IL-6) and matrix metalloproteinase-13 (MMP-13). This study evaluates and compares the modulatory effects of intra-articular hyaluronic acid (HA) and piroxicam (PIRO) on IL-6 and MMP-13 levels in a rat model of OA. Methods: OA was surgically induced in 24 Sprague Dawley rats and animals were randomly assigned to three groups (control, HA, and PIRO) with 08 rats in each group. saline water, hyaluronic acid and piroxicam were administered intra-articularly once weekly for four weeks. Synovial lavage samples were collected post-treatment and analyzed for IL-6 and MMP-13 levels. Data was analyzed using SPSS, (p≤0.05) was considered statistically significant. Results: Both HA and PIRO significantly reduced synovial IL-6 (p=0.001) and MMP-13 (p=0.003) and (p<0.00 l) respectively when compared to control group. No significant difference was found between HA and PIRO groups (p>0.05), suggesting comparable anti-inflammatory efficacy. Conclusion: Both hyaluronic acid and piroxicam equally reduce IL-6 and MMP-13 levels in the synovial lavage fluid of a rat model of osteoarthritis.

Piroxicam (PRX), a non-steroidal anti-inflammatory drug (NSAID), is classified as a biopharmaceutical classification system class II (high permeability and low solubility), which limits its bioavailability. Enhancement of the dissolution rate is a key strategy to enhance the absorption. Solid dispersion systems, particularly when combined with amphiphilic multiple co-block polymers, offer a promising approach to address this challenge. This study aimed to investigate the effect of Poloxamer 188 (P188) and the solid dispersion technique on the solubility and dissolution rate of PRX. Polyethylene glycol (PEG) 4000-based solid dispersions containing PRX were prepared using varying concentrations of Poloxamer 188 surfactant through the fusion method. The solid dispersions were evaluated for saturated solubility in water for 24 hours. Selected formulations were further characterized using thermal analysis and vibrational spectroscopy. The optimized solid dispersion formulation was filled into capsules, and a dissolution assay was carried out to compare its performance with that of pure PRX capsules. The optimized formula, comprising 3% P188 and PEG4000, demonstrated a significant enhancement in saturation solubility parameters (p < 0.05), specifically the Cmax/S0 ratio. Additionally, dissolution testing showed a 22.22% increase in the dissolution rate of the PRX solid dispersion capsules compared to pure PRX capsules. In conclusion, P188-based solid dispersion containing PRX enhanced the solubility and dissolution rate, potentially improving therapeutic efficacy.

Enhanced anti-inflammatory efficacy of a new piroxicam analogue through the MEK/ERK/NF-κB pathway in vitro and in vivo.

IntroductionDrug repurposing is gaining consideration in cancer due to the challenges of poor outcomes and resistance associated with the current conventional modalities. Non-steroidal anti-inflammatory drugs (NSAIDs), widely used for treating inflammation, are being explored for their potential efficacy in cancer treatment, including prostate cancer (PCa). This study aims to evaluate the efficacy of Piroxicam (PXM), an NSAID, in enhancing the sensitivity of PCa cells to chemotherapy and hormonal drugs.MethodsComputational analysis was conducted to identify differentially expressed genes between our established murine PCa cell models, PLum-AD (androgen-dependent) and PLum-AI (androgen-independent), to uncover potential therapeutic targets. In two-dimensional (2D) cell culture, cell proliferation, viability, and migration assays were performed on PLum-AD and PLum-AI cells treated with PXM alone or in combination with docetaxel (Doc) or enzalutamide (Enz). Additionally, the impact of these treatments on stem-like progenitor cells was assessed using three-dimensional (3D)-Matrigel™-based sphere-forming and organoid formation assays.ResultsTranscriptomic analysis revealed that inflammatory pathways are enriched during PCa progression, making them viable targets for NSAID-based interventions. Single treatment of PXM demonstrated significant anti-cancer effects on PLum-AD and PLum-AI cells, evidenced by reduced cell proliferation, viability, migration, sphere growth, and organoid growth.DiscussionImportantly, PXM treatment in combination with Doc or Enz resulted in more pronounced antineoplastic effects compared to single-drug exposure. Our work suggests PXM as a potential adjunctive therapy to enhance the efficacy of conventional treatments in PCa patients.

Using a sensitive screen-printed electrode based on printex L6 and polyaniline activated carbon for piroxicam detection.

Điện cực than thuỷ tinh (GC) được biến tính bằng vật liệu composite MnO2/GO và AgNPs/MnO2/GO. Sau quá trình khử điện hóa, vật liệu khử MnO2/ErGO và AgNPs/MnO2/ErGO có diện tích bề mặt hoạt động điện hóa lớn, lần lượt là 0,079 cm2 và 0,087 cm2; điện trở truyền tải điện tích (Rct) là khá nhỏ, lần lượt là 0,188 kW và 0,077 kW. Trong nghiên cứu này, hai chất kháng sinh, gồm chloramphenicol (CAP) và tinidazol (TNZ) hấp phụ lên bề mặt điện cực MnO2/ErGO-GCE và kháng sinh ofloxacine (OFX) hấp phụ lên bề mặt điện cực AgNPs/MnO2/ErGO-GCE. Kết quả cho thấy quá trình hấp phụ xảy ra trong khoảng 3 phút và tuân theo mô hình động học biểu kiến bậc 2 với các giá trị dung lượng hấp phụ bão hòa lần lượt là 1310,16, 1873,41 và 1140,93 mg.g-1. Riêng đối với chất kháng viêm piroxicam (PRX), quá trình khuếch tán bên ngoài lớp dung dịch – điện cực AgNPs/MnO2/ErGO-GCE chiếm ưu thế hơn so với quá trình hấp phụ, trong đó quá trình khuếch tán xảy ra nhanh với thời gian dưới 30 s. Nghiên cứu này đã bổ sung và giải thích cơ chế quá trình khuếch tán – hấp phụ các chất kháng sinh và kháng viêm trên bề mặt điện cực biến tính.

Background: Piroxicam (PRX), a nonsteroidal anti-inflammatory drug, exhibits poor aqueous solubility, limiting its therapeutic efficacy. Enhancing solubility can directly improve bioavailability and therapeutic effectiveness. This study explores the development of a new solid dispersion (SD) system of PRX using polyvinylpyrrolidone (PVP K30) as a carrier by MW-assisted method. Methods: The involvement of microwave (MW) in the solvent evaporation method is a newer concept aimed at enhancing the solubility and in vivo bioavailability of PRX. Various ratios of PRX: PVPK30 (1:5, 1:7, 1:9, and 1:11 w/w) were evaluated using conventional and MW-assisted solvent evaporation methods and conducted in vitro dissolution studies. Results: The optimized MW-assisted formulation (1:7 w/w) exhibited 94.69±0.24% drug release in 15 minutes, showing a 5.37-fold increase compared to pure PRX (17.63%) and surpassing the marketed drug release (90.82±0.39%). Fourier Transform Infrared, Differential Scanning Calorimetry, Thermogravimetric analysis, Scanning Electron Microscopy, and powdered X-ray diffraction authenticated the OF. In vivo studies demonstrated significant enhancements (p<0.0001) compared to control. The anti-inflammatory activity showed increased paw oedema inhibition (44.4±0.4%) compared to control and pure PRX (35.37±0.3%). The analgesic activity of OF demonstrated improved pain response time (10.6±0.8 seconds) compared to control (4.2±0.5 seconds) and pure PRX (8.1±0.7 seconds). Conclusion: The SD developed via the MW-assisted drug formulation technique significantly enhances the solubility, bioavailability, and therapeutic efficacy of PRX, offering a potential strategy to improve clinical outcomes for similar drugs with solubility challenges.

A precise, simple, economical and accurate UV spectroscopy-assisted method has been developed to estimate piroxicam (PRXM) in pure API and tablet dosage form. The absorbance maxima of PRXM were found at 357nm λmax using water (H2O) and methanol (MeOH) in a ratio of 40:60 V/V as a solvent. For concentrations between 2 μg mL-1 - 12 μg mL-1, the procedure adheres to Beer's law with an R2 value of 0.9992, the linearity was found in the calibration curve between absorbance and concentration in accordance with the line equation y=0.0508x+0.0085. The LOD and LOQ were found to be 0.90 µg mL-1 and 2.74 µg mL-1, respectively. The proposed method was effectively used to calculate PRXM in bulk drug and pharmaceutical formulations without common excipient influence and the % RSD was found 0.79, with an average % recovery of 99.57 %. The developed method was validated in accordance with ICH Q2 (R1) guidelines.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and associated oxidative and glycative stress, contributing to disease progression and complications. Non-steroidal anti-inflammatory drugs (NSAIDs) such as piroxicam (PIR) and naproxen (NAP) have shown potential repurposable antidiabetic effects, partly through inhibition of dipeptidyl peptidase-4 (DPP-4), an enzyme regulating glucose metabolism. This study evaluated PIR and NAP (10 μM) in a glucolipotoxic (GLT) cellular model of insulin resistance. C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. GLT conditions elevated intracellular reactive oxygen species (ROS) by 73.5% ± 9.4% (p < 0.05). Both NAP and PIR significantly reduced ROS levels by 87.0% ± 14.6% and 74.1% ± 9.9%, respectively (p < 0.05). PIR (10 μM) was prioritized for further assessment for effects on glucose uptake in the same model where it enhanced glucose uptake by 191.7% ± 98.6% (p < 0.05). Subsequently, PIR’s biochemical activities (40 ppm) were evaluated in cell-free assays. PIR significantly inhibited AGE formation in the BSA-methylglyoxal model, reducing fluorescence by 245.4% ± 36.3% at day 7 and 145.2% ± 29.2% at day 14 (p < 0.001). It showed a protective trend against amyloid fibril formation, decreasing Congo red absorbance by 55.0% ± 3.8%, although this effect was not statistically significant (p < 0.005). Pancreatic lipase inhibition was limited (~12%, p < 0.05), indicating a lack of anti-obesity potential at tested concentrations. While PIR shows promising antioxidative and antiglycation effects, further studies are needed to fully elucidate its clinical relevance in T2DM management.

Development of ZnO-Pd/Bi2O3 nanocomposite modified carbon paste electrode as a sensor for the simultaneous determination of piroxicam and naproxen

Solar light driven degradation of piroxicam and paracetamol by heterogeneous photocatalytic fenton system: Process optimization, mechanistic studies and toxicity assessment

Cucurbit[7]uril-based host–guest complexes for improving bioavailability and reducing side effects of piroxicam

Objectives In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach, i.e., hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected. Method Solid dispersions of PRX were formulated using two hydrotropes, viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 32factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated. Key findings SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1–F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX. Conclusion An evident tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.

A simple, rapid, sensitive, and cost-effective green solvent-assisted reverse-phase high-performance liquid chromatographic technique, coupled with a photodiode array detector, was developed and validated for the estimation of piroxicam (PRXM). The chromatographic separation was achieved by using a C-18 (250 × 4.6) mm, 5-μm stationary phase and a mobile phase consisting of methanol and 0.1% ortho-phosphoric acid in water in a ratio of (80:20) v/v at a flow rate of 1ml/min. The detection was carried out at a wavelength of 254nm with a constant injection volume of 10μL throughout the analysis. The calibration curve was observed to be linear over the optimum concentration range of 50-300μgmL-1, with an R2 value of 0.9995. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. Various parameters like selectivity/specificity, accuracy/recovery, linearity, precision, detection limit, quantitation limit, robustness and stability of analyte in solution were performed for the method validation. The PRXM was evaluated under stressed conditions, including acidic, basic, oxidative, thermal and photolytic, as per ICH Q1 (R2) guidelines. Significant degradation was observed in acidic and basic degradation conditions. Conversely, the drug substance showed stability when exposed to oxidative, photolytic and thermal degradation conditions.

Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system.

A chemometric method, partial least squares regression (PLS) was applied for the simultaneous determination of piroxicam (PIR), naproxen (NAP), diclofenac sodium (DIC), and mefenamic acid (MEF) in synthetic mixtures and commercial formulations. The proposed method is based on the use of spectrophotometric data coupled with PLS multivariate calibration. The Spectra of drugs were recorded at concentrations in the linear range of 1.0 - 10 μg mL-1 for NAP and from 1.0 - 20 μg mL-1 for PIR, DIC, and MEF. 34 sets of mixtures were used for calibration and 10 sets of mixtures were used for validation in the wavelength range of 200 to 400 nm with the wavelength interval λ = 1 nm in methanol. This method has been used successfully to quantify drugs in pharmaceutical formulations with no interference from excipients. The proposed method is simple, quick, and can be used as an alternative analysis tool in drug and formulation quality control as well as process control.

Objective Inflammation is a natural response of the organism, involving events responsible for releasing chemical mediators and requiring treatments of symptoms such as pain, redness, heat, swelling, and loss of tissue function. Piroxicam (PRX) is a non-steroidal anti-inflammatory drug with the effect of nonselective COX inhibitor activity; however, it shows poor bioavailability caused by the poor and slow water solubility. In this study, we developed PRX nanosuspensions with 200–500 nm in diameter to increase the bioavailability of PRX by improving its solubility. Methods PRX nanosuspensions were fabricated by High pressure homogenization method with PVA, SDS and Tween 80. The nanosuspensions were characterized by XRD, FTIR, DSC, and in vitro release. In vivo pharmacokinetic properties and anti-inflammatory effects were also investigated in rabbits. Results PRX nanosuspensions significantly increased the solubility (14.89 ± 0.03 mg/L for pure PRX and 16.75 ± 0.05 mg/L for PRX nanosuspensions) and dissolution rate as compared to the pure PRX (p < 0.05). Orally administered PRX nanosuspension (AUC 0-t is 49.26 ± 4.29 μg/mL × h) significantly improved the bioavailability of PRX (AUC 0-t is 28.40 ± 12.11 μg/mL × h). The anti-inflammatory effect of PRX nanosuspension was also investigated in rabbits and it was observed that PRX nanosuspension treatment significantly improved the inhibition of COX-2 and NFκB expression as compared to the PRX treatment (p < 0.05). Conclusions The results in this study indicate that PRX nanosuspension is a promising nanomedicine for enhancing the anti-inflammatory activity of PRX and has a high potential for the treatment of inflammation.

Abstract This paper focuses on the development of hollow starch nanoparticles (HSNPs) as promising carriers for poorly soluble drugs. A new and efficient method is presented, based on an in situ gas‐foaming/salt‐leaching process within individual starch nanoparticles prepared by a solvent displacement technique. Characterization using dynamic light scattering, transmission electron microscopy, and nitrogen adsorption/desorption analysis confirmed the successful preparation of HSNPs. Solid dispersion systems with piroxicam (PRX) as a model drug were formulated to evaluate HSNPs’ potential as poorly water‐soluble drug carriers. Solid‐state properties, dissolution behavior and stability of PRX‐HSNPs solid dispersions were investigated. In vitro dissolution studies revealed that using hydrophilic HSNPs as carriers significantly improved the release of PRX. Solid‐state characterization showed that the main reason for the improved dissolution was the adsorption of PRX on the outer and inner surfaces of the HSNPs in an amorphous state. Stability studies demonstrated that the amorphous nature of loaded PRX remained unaffected even after 12 weeks of storage at 75 % relative humidity. Accordingly, the proposed HSNPs offer a promising alternative for the delivery of poorly water‐soluble drugs. In addition, the synthesis strategy demonstrated for HSNPs is easy, efficient and could be extended to the preparation of other hollow polymeric nanoparticles.

Rapid and sensitive determination of Piroxicam by N-doped carbon dots prepared by plant soot