Piroxicam Solution Research Articles

Evaluation of process influencing factors, degradation products, toxicity evolution and matrix-related effects during electro-Fenton removal of piroxicam from waters

The degradation kinetics, the operational influencing factors, the determination of short-chain organic by-products, the mineralization degree, the evolution of residual toxicity, as well as the treatment of complex matrices were systematically investigated on removal of piroxicam by Electro-Fenton process (EF), due to its persistence and low removal in water matrices. The second order reaction rate constant between piroxicam and hydroxyl radical (•OH) was determined as (2.19 ± 0.01) × 109 M−1 s−1. It was found that the process was able to almost completely mineralize 0.08 mM piroxicam solution (92% TOC removal) at 6 h treatment. Based on identification of short-chain carboxylic acids, released inorganic ions and the removal of total organic carbon, a schematic proposal of piroxicam degradation by EF treatment was done. The evolution of the acute toxicity of treated piroxicam solution was monitored by Microtox method, showing a significant toxicity reduction at 180 min treatment. Remarkably, piroxicam in simulated urine and hospital wastewater was completely degraded after 120 min of EF treatment. Therefore, the results indicate that the tested EF process constitutes an efficient option for the elimination of piroxicam in aqueous media.

Permeability of Piroxicam with Sodium Lauryl Sulfate as Surfactant

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) which have characteristic insoluble in water and poorly fluidity. The profile absorption from piroxicam was depend on its dissolution rate in the gastrointestinal tract (GI). To improve the solubility in the water, it can used Sodium Lauryl Sulfate (SLS) as a surfactant which have mechanism by forming a micelle. The aim of this study was to measure the influence gradiet concentration of SLS with Piroxicam absorption that can observe by inverted intestinal sac method. The concentration of piroxicam solution that added by SLS are 1, 2, and 3% respectively. The preparation method using Crane and Wilson tube containing mucosal fluid. After preparation, it was taken at 37°C in waterbath and added with serosal solution to intestinal sac by turned upside down and tied to a cannula. The sample was placed in the tube containing mucosal fluid and constantly flowing by oxygen gas. To measure the absorsion of piroxicam that used serosal solution which every 15 minutes was taken on tube. After this, it was diluted using Ba(OH)2 and ZnSO4 then continuous with separating process. The absorbant of supernatant was measured using Spectrophotometer UV-Vis. Data analyse was calculated by one-way ANOVA. According to Pm, the values 0.25x10-3 cm/minute (0% SLS), 0.39x10-3 cm/minute (1% SLS), 1.45x10-3 cm/minute (2% SLS) and 1.26x10-3 cm/minute (3% SLS) respectively. In conclusion, 2 % SLS significantly give the highest absorption of piroxicam by altering the membrane permeability.

UV-vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup.

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays.

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7–34 μm and was controlled by the PRX concentration in the feed solution (15–25 g L–1), antisolvent/solvent volume ratio (5–30), and type of antisolvent (Milli-Q water or 0.1–0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L–1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.

The Influence of Polyvinyl Pyrrolidone (PVP) on Piroxicam Absorption with Everted Intestinal SAC Method

Oral drug absorption was highly influenced by dissolution rate, especially for poorly and insoluble drugs. Piroxicam is a nonsteroidal anti-inflammatory drug that is practically insoluble in water. The oral absorption rate of piroxicam is dependent on its dissolution rate in the GI tract. Polyvinyl Pyrrolidone (PVP) as surfactant can increase drug solubility by means of a micelle forming mechanism. The aim of the study was to know the influence of addition and variation of Polyvinyl Pyrrolidone (PVP) on Piroxicam absorption with everted intestinal sac method. The concentration of piroxicam solution was prepared by PVP in 1.0, 2.0 and 3.0 % respectively. Crane and Wilson tube containing 75 ml of the mucosal fluid was taken at 37 0 C in waterbath. Than, serosal solution of 1.5 ml was added to intestinal sac by turned upside down and tied to a cannula, then put into the tube containing the mucosal fluid and constantly flowing oxygen gas. Serosal solution of 1 ml were taken every 15 minutes and then diluted with 2 ml of Ba (OH) 2 and 2 ml of ZnSO4 then centrifuge until 25 minute. The absorbant of supernatant was measured by UV spectrophotometer and data analyse was calculated by one-way ANAVA. PVP at 1%,2% and 3% increased piroxicam absorption from the phosphate buffer pH 7.5 compared with negative control. According to P app , the values were 2.52 ± 0.43 cm/minute (negative control), 3.41 ± 2.17 cm/minute (1% PVP), 2.75 ± 1.14 cm/minute (2% PVP) and 4.77 ± 4.93 cm/minute (3% PVP) respectively. In conclusion. Lower doses of the surfactant (1%, 2%, and 3% PVP) significantly increased absorption of the drug by altering the membrane permeability. Keywords: Piroxicam, absorption, in vitro, PVP

Sugar coated ceramic nanocarriers for the oral delivery of hydrophobic drugs: formulation, optimization and evaluation

In order to enhance the delivery of poorly-soluble drugs, we have explored aquasomes (three-layered, ceramic core based, oligosaccharide coated nanoparticles) as potential carriers for the delivery of model hydrophobic drug piroxicam (log P = 3.1). Ceramic nanoparticles were prepared using two techniques; namely, co-precipitation by refluxing and co-precipitation by sonication. Core preparation was finally done using sonication approach; based on the higher % yield (42.4 ± 0.4%) and shorter duration (1 day) compared to the reflux method (27.4 ± 2.05%, 6 days). Lactose loading onto ceramic core was achieved using adsorption. Colorimetric analysis of lactose coating was done using Anthrone method. Optimization of process variables namely, incubation time and core to coat ratio (for sugar loading) was carried out. Optimum time of incubation was 3 h and the core to coat ratio was 4:1. The drug loading was achieved by incubating the sugar loaded cores in different concentrations of piroxicam solution and it was found that 1.5% w/v piroxicam was optimal. Structural characterization using Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed the presence of sugar coating onto the core. Morphological evaluation using transmission electron microscopy (TEM) revealed spherical nanoparticles (size 56.56 ± 5.93 nm for lactose coated core and 184.75 ± 13.78 nm for piroxicam loaded aquasomes) confirming the nanometric dimensions.

Rheological characterization and in vivo evaluation of thermosensitive poloxamer-based hydrogel for intramuscular injection of piroxicam

To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel. However, sodium chloride did the opposite. The thermosensitive injectable gel composed of 2.5% piroxicam, 15% P 407, 17% P 188, 0.01% sodium hydroxide and 1.6% sodium chloride was instantly applied to practical industrial product, since it was easy to administer intramuscularly and gelled quickly in the body. The drug was dissolved out of the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. Sodium chloride barely affected the dissolution mechanism or dissolution rate of the drug from the injectable gels. Furthermore, it maintained the plasma concentrations of drug for 4 days and gave a 150-fold higher AUC compared to piroxicam solution. Thus, it would be practically useful for delivering piroxicam in a pattern that allows sustained release for a long time, leading to better bioavailability.

Chemiluminescence method for the determination of piroxicam by the enhancement of the tris‐(4,7‐diphenyl‐1,10‐phenanthrolinedisulphonic acid) ruthenium(II) (RuBPS)–cerium(IV) system and its application

A simple, rapid chemiluminescence (CL) method was described for the determination of piroxicam, a commonly used analgesic agent drug. A strong CL signal was detected when cerium(IV) sulphate was injected into tris-(4,7-diphenyl-1,10-phenanthrolinedisulphonic acid) ruthenium(II) (RuBPS)-piroxicam solution. The CL signal was proportional to the concentration of piroxicam in the range 2.8 x 10(-8)-1.2 x 10(-5) mol/L. The detection limit was 2 x 10(-8) mol/L and the relative standard deviation (RSD) was 3.7% (c = 7.0 x 10(-7) mol/L piroxicam; n = 11). The proposed method was applied to the determination of piroxicam in pharmaceutical preparations in capsules, spiked serum and urine samples with satisfactory results.

The effect of piroxicam on the formation of postoperative, intraabdominal adhesion in rats

Background/Aims:Peritoneal adhesions are fibrous bands of tissues formed between organs that are normally separated and/or between organs and the internal body wall after peritoneal injury. Antiinflammatory agents were used to reduce the initial inflammatory response to tissue injury and, hence, the subsequent formation of adhesion. The aim of this study was to investigate the effect of intraperitoneal instillation of piroxicam on intraperitoneal adhesions.Methods:Eighty Wistar rats were subjected to standardized lesion by using the scraping model and were randomly divided into four groups. Group I (control) received no treatment; groups II, III, and IV received 10-12.5 mL of 0.05, 0.1, and 0.2 mg/mL piroxicam solution, respectively, after surgery. On the 14th postoperative day, the adhesion intensity score, inflammatory cell reaction, and the number of adhesion bands were determined.Results:There were no rats with grade 0 adhesions in the control group. There were 10 rats (50%) with grade 2 and eight rats (40%) with grade 3 adhesions. The adhesion intensity (P < 0.0001) and the number of adhesion bands (P < 0.001) were significantly lower in groups III and IV. No significant difference was observed in the adhesion intensity or the number of adhesion bands between groups I and II.Conclusions:Intraperitoneal instillation of piroxicam solution might be useful for preventing peritoneal adhesions.

The influence of tween 80 and polyethylen glycol 400 on piroxicam absorption from rat intestinal lumen in situ

Oral drug absorption administered is highly influenced by dissolution rate, especially for poorly and insoluble drugs. Tween 80 and polyethylene glycol 400 (PEG 400) as surfactant an increase drug solubility by means of a micelle forming mechanism. The aim of the study wasto know the influence of addition and variation of Tween 80 and PEG 400 on the absorption of piroxicam from rat intestinal lumen in situ. Piroxicam solution in pH 7.5 phosphate buffer was prepared with the same concentration in three kinds based on the addition concentration of Tween 80 and PEG 400, they were 1.0, 1.5 and 2.0 % respectively. The male rats of 130-180 grams body weight fasted were for 24 hours before treatment. The rats were anaesthetized with 5x10-3 mL/g BW 40% urethan subcutaneously. Piroxicam unabsorbed fraction was measured in a spectrophotometer at 353 nm, and then calculate Papp (Appear Permeability). The data obtained were calculated according to Kolmogorov-Smirnov and one-way ANAVA then continued by a t-test (95% confidence level). Tween 80 at 10% and 1.5% increased piroxicam absorption from the phosphate buffer pH 7.5 but decreased with Tween 80 2.0%. According to Papp, thevalues were 0.3929 cm/minute (1.5% Tween 80), 0.3507 cm/minute (1.0% Tween 80) and 0.2593 cm/minute (2.0% Tween 80) respectively. PEG 400 at 2.0 % rised piroxicam absorption from the phosphate buffer pH 7.5 but no with influence PEG 400 1.5 % concentration one way ANAVA. Key words : Tween 80, Polyethylen glycol 400, piroxicam, in situ absorption

Improved solubility and dissolution rate of piroxicam using gelucire 44/14 and labrasol

Piroxicam is a nonsteroidal anti-inflammatory drug that is characterized by low solubility-high permeability. The present study was designed to improve the dissolution rate of piroxicam at the physiological pH's through its increased solubility by preparing semi-solid dispersions of drug using Gelucires and Labrasol. These excipients are essentially characterized by their melting points and HLB (hydrophilic–lipophilic balance) values. The dissolution tests of the preparations were performed in the media with different pH's. Differential scanning calorimetry (DSC), were used to examine the interaction between piroxicam and excipients. Gelucire 44/14 and Labrasol at the concentration of 15% w/v in water provided 20- and 50-fold increase in the solubility of piroxicam, respectively. The semi-solid dispersion containing 1/20 of drug/excipient mixture (20% Gelucire 44/14 and 80% Labrasol in w/w) produced the dissolution not less than 85% of piroxicam within 30 min in each dissolution media (simulated gastric fluid (SGF), pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). DSC analysis of this semi-solid dispersion indicated that there was no chemical reaction between the drug and excipients, and that a solid-state solution of piroxicam with excipient formed.

PREPARATION AND EVALUATION OF PIROXICAM - PLURONIC SOLID DISPERSIONS

With an objective of enhancing the dissolution rate of piroxicam (PXM), solid dispersions(SDs) of piroxicam were prepared using different grades of pluronic F-68 (Pl. F-68), pluronicF-98 (Pl. F-98), and pluronic F-127 (Pl. F-127) adopting the solvent evaporation technique.The solid dispersions were prepared at different (drug: polymer) ratio (1:1, 1:3 and 1:5).Piroxicam- pluronic solid dispersions were investigated by inferared spectroscopy (IR), x-raydiffraction (XRD) and differential scanning calorimetry (DSC). The IR spectra prevailed nochemical interaction between the drug and copolymer. The powder x-ray diffraction (XRD)patterns and differential scanning calorimetry (DSC) thermograms demonstrated thatpiroxicam was existed in a solid solution state in the SD. Phase diagram for solid dispersion ofpiroxicam in pluronic F-98 indicated that the solid solution of piroxicam was obtained at aconcentration of PXM less than 35% in the SD. The stability study was carried out for the soliddispersion prepared at 1:1 (piroxicam/ Pl. F-98) at 40 ° for 40 weeks prevailed that; the drug isstable during the storage period in the dispersion. The solubility study of piroxicam was carriedout at different concentrations of pluronics, also the dissolution rate of the drug was improvedeither by physical mixture or the solid dispersions.

Piroxicam-Induced Regression of Intestinal Adenomatous Polyps in APC Δ474 Mice

Mutation of adenomatous polyposis coli (APC) gene results in incidence or development of polyps and colorectal cancer. It has been reported that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cell growth, cause cell cycle arrest, and induce apoptosis. The aims of this study are to investigate chemopreventive effects of piroxicam and elucidate its mechanism. All APC j 474 mice have intestinal polyps. Thirty-five APC j 474 mice were divided into three groups: 0.005% solution of piroxicam in tap water was given for P group ( n = 15) and 0.001% solution for P' group ( n = 5), and water without piroxicam for C group ( n = 15) from 4 weeks of age to 12 weeks, respectively. All mice were sacrificed at the 12th week after birth. Hematoxylin-eosin staining for number and size of polyps, immunohistochemical staining for cyclooxygenase (COX)-1 and -2, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), TUNEL method, and Western blot analysis of COX-2 and VEGF were performed. Polyps were divided into two types of large polyps of S 300 w m in diameter and small polyps of <300 w m. The number of large polyps in P group decreased significantly compared with C group ( p < .0001), but without significant difference in small polyps. There were no significant differences in PCNA index in both of large and small polyps among the three groups. Apoptotic index of polyps in P group increased more than those in C group ( p < .05). There was immunohistochemically no significant difference in COX-1 positivity of normal intestinal epithelia and adenomas among three groups. Both numbers of VEGF-positive cells and COX-2 positive cells in the stroma of the small intestine were significantly downregulated in P group ( p < .05). COX-2 expression was inhibited in dose-dependent manner without significant difference. There were no significant differences in VEGF expression between P' and C groups. In conclusion, piroxicam suppressed the development of large polyps in APC j 474 mice by inducing apoptosis and inhibiting VEGF expression in interstitial cells of polyps.

Enhancement of Dissolution and Bioavailability of Piroxicam in Solid Dispersion Systems

Solid dispersion systems of water-insoluble piroxicam in polyethylene glycol (PEG) 4000 and in urea were prepared by fusion and solvent methods and were characterized in this study. The in vitro dissolution studies showed that the dispersion systems containing piroxicam and PEG4000 or urea gave faster dissolution than the corresponding simple mixtures. The differential scanning calorimetry (DSC) study indicated that the piroxicam-PEG system prepared by the fusion method is a solid dispersion, while the piroxicam-urea system prepared by the solvent method is likely to be a solid solution of piroxicam in urea. The storage testings showed that all dispersions were stable, except that uptake of water during storage may occur in the PEG system. A single-dose study with rabbits showed that the dispersion systems provided statistically significant to a higher extent and rate of bioavailability than the corresponding physical mixture (p < 0.05).

The effects of intraperitoneal piroxicam and low molecular weight heparin in prevention of adhesion reformation in rat uterine horn.

Our objective was to determine the effectiveness of intraperitoneal single dose piroxicam and low molecular weight heparin (LMWH) on prevention of adhesion reformation in the rat uterine horn. This study was carried out in the Surgical Research Laboratory, at Erciyes University. A standard lesion was created by unipolar electrocautery in 72 uterine horns of 36 female Wistar-Albino rats. After 2 weeks, adhesion formation scores were determined and adhesiolysis was performed in the second-look laparotomy. Animals were then randomly assigned into three groups. Each group contained 12 animals: group 1 was the control group where no adjuvant was given; in group 2, 1 ml 50 U Axa IC/ml solution LMWH was applied to the horns postoperatively, and in group 3, 1 ml 2 mg/ml piroxicam solution was applied to the horns after adhesiolysis. Two weeks later the rats were killed and adhesion reformation was evaluated. The number of horns with adhesion formation and the cumulative scores were not significantly different among the three groups in the second-look laparotomies, but after third-look laparotomies, the number of horns with adhesion reformation, after calculating the extent, severity and total scores of adhesion reformation, was found to be significantly less in LMWH and piroxicam groups than in the control group. Also, the effectiveness of piroxicam was significantly greater in all scores of adhesion reformation than LMWH was. In conclusion, both LMWH and piroxicam doses reduce adhesion reformation in the rat uterine horn, but the effectiveness of piroxicam is significantly greater than that of LMWH.

Evaluation of a positively charged submicron emulsion of piroxicam on the rabbit corneum healing process following alkali burn

The effect of piroxicam in three different formulations was tested on rabbits for 28 days in an alkali burn model. The ulceration healing process was determined by evaluating the severity of the burn (scored from 0 to 5), and the re-epithelization healing process was measured by the area of the defects. The results indicated that the piroxicam positively charged submicron emulsion was the most effective formulation in lowering the ulcerative cornea score while the piroxicam positively charged emulsion and the blank emulsion were more effective in promoting the re-epithelization healing process. The piroxicam solution elicited the slowest healing re-epithelization rate after 28 days and was unable to complete the entire healing process. The new positively charged submicron emulsion formulation of piroxicam had a pronounced effect on both the ulceration rate and epithelial defects in the management of corneal alkali-burning.

Characterization of solid dispersions of piroxicam/polyethylene glycol 4000

Piroxicam is a nonsteroid anti-inflammatory that is poorly soluble in water. The present study describes the formulation of solid dispersions of the drug designed to increase solubility. X-ray diffraction, infrared spectroscopy and DSC were used to examine the physico-chemical characteristics of solid dispersions of piroxicam and polyethylene glycol 4000 (PEG 4000) prepared by the melting-solvent method, using percentage proportional compositions ranging from 10:90 to 80:20. The results showed that there was no chemical interaction between the drug and the polymer, and that a solid solution of piroxicam : PEG 4000 formed at concentrations of the drug below 30%. In addition, dispersions of small crystals of piroxicam were noted in the soluble carrier, however, a eutectic mixture of the drug : polymer binary system tested was not obtained.

Sensitivity to thimerosal and photosensitivity to piroxicam

17 patients allergic to thimerosal, with no previous history of photosensitivity or piroxicam ingestion, 2 patients with piroxicam-induced photosensitivity, and 10 controls were patch or photopatch tested, with 1 or more of the following: thimerosal, thiosalicylic acid, irradiated and non-irradiated solutions of piroxicam alone, L-cysteine alone and piroxicam plus L-cysteine, and piroxicam in petrolatum., The results of the tests supported the hypothesis that there are cross-reactions between thiosalicylic acid and prioxicam, a photosensitizer. The mechanism of the cross-reactions may involve photoproducts of piroxicam and L-cysteine, as patients allergic to thiosalicylic acid, who have positive photopatch tests to piroxicam, also had positive patch tests to the irradiated solution of piroxicam plus L-cysteine.

A case of piroxicam-induced photosensitive dermatitis

We report a case of piroxicam-induced photosensitive dermatitis in a 54-year-old female. She had taken oral piroxicam and was exposed to the sunlight on her way home for a few minutes. Several hours after the sun-exposure she developed well-defined, confluent, erythematous plaques and numerous vesicobullae with pruritus and prickling sensation on the sun-exposed areas. A phototest was done on her first visit. The minimal erythemogenic dose(2J/) of ultraviolet(UV) A was markedly decreased whereas that of UVB was within a normal limit. Visible light irradiation for 30 minutes did not cause skin lesions. Six months after the initial skin lesions, a photopatch test with 1% and 10% piroxicam solution followed by UVA(10J/) irradiation showed positive responses on both concentrations.