Diclofenac Sodium Solution Research Articles

Effect of oxidated golden shower on the adsorption of diclofenac sodium in wastewater

AbstractThis research aimed to modify activated carbon into oxidated activated carbon because it can effectively remove diclofenac sodium (DCF) and increase the adsorption capability. In this study of the several variations of initial concentration and contact time, those variations affected the optimal result. To determine, the removal efficiency of diclofenac sodium used Golden Shower Activated Carbon based on the contact time variation and the optimum contact time compared to Golden Shower Oxidated Activated Carbon as adsorbent on the batch method and to know the isotherm model and the kinetic model of the adsorbent on the adsorption in diclofenac sodium solution. The pHPZC for GSHAC and GSHOAC were 2.4 and 9.3. The optimum contact time for GSHAC was 225 min with the capacity (qt = 184.71 mg/g). The optimum contact time for GSHOAC was 169 min with the capacity (qt = 188.34 mg/g). The Isotherm model, kinetics model, and the physical characterization of the biosorbent were thoroughly investigated. The isotherm model chosen in the adsorption process for GSHAC and GSHOAC was the Langmuir model (R2 = 0.985 and R2 = 0.973). The pseudo‐second‐order for GSHAC and GSHOAC was confirmed to be a kinetic pseudo‐second‐order model of the adsorption with R2 values of 0.9566 and 0.9986. The model represents that the reaction from the adsorbent to the solution was double the initial concentration. Based on SEM analysis after the adsorption process, it was found that flakes of adsorbent before adsorption had many layers of pores, causing an irregular texture after adsorption showed that GSHAC and GSHOAC were fragmented and had many layers of pores that were closed and tight because it adsorbed DCF.

Efficacy of mixed diclofenac solutions against root canal biofilms.

The objective of this research was to evaluate the efficacy of diclofenac sodium solutions, with or without cetrimide (CTR) added, against polymicrobial root canal biofilms grown in dentin specimens. The study groups were: (1) 5% diclofenac sodium (DCS); (2) 2.5% DCS; (3) 2.5% DCS + 0. 2% CTR; (4) 2.5% DCS + 0.4% CTR and (5) 0.9% saline solution (SS) as the control. After 5 min of solution contact with the biofilms, the antimicrobial activity was evaluated by means of the adenosine triphosphate (ATP) assay as well as confocal laser scanning microscopy (CLSM). Microbial quantification was indicated as the percentage reduction of relative light units (RLUs) for the ATP assay, the Log10 total biovolume and the viability percentage (green cells) for CLSM. Solutions of 2.5% DCS + 0.4% CTR and 5% DCS showed the highest antimicrobial efficacy. Cetrimide increased the antibiofilm activity of diclofenac sodium against endodontic biofilms.

Warm acupuncture stimulation improves cartilage damage and motor function by regulating JAK2/STAT3 signaling pathway in rabbits with knee osteoarthritis

To observe the effect of warm acupuncture on the expression of Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway and inflammatory factors of articular cartilage in rabbits with knee osteoarthritis (KOA), so as to explore its underlying mechanisms in improving KOA. New Zea-land rabbits were randomly divided into blank, model, warm acupuncture and medication groups (12 rabbits in each group). The KOA model was prepared by using the right hind limb tubular plaster extension fixation method. The rabbits in the warm acupuncture group received acupuncture of "Neixiyan"(EX-LE4),"Waixiyan"(ST35),"Heding"(EX-LE2) and "Zusanli"(ST36), followed by attaching an ignited moxa-stick segment to the acupuncture-handle. The treatment was conducted for 15 min, once a week for 4 weeks. The rabbits in the medication group received gavage of diclofenac sodium solution(0.35 mg/kg), once daily for 4 weeks. The dysfunction severity state of the rabbit's knee-joint was evaluated using Lequesne scale (0-3 points), and the histopathological changes of cartilage were observed under microscope after H.E. staining and the state of distribution of chondrocytes in different layers and the extracellular matrix was assessed using Mankin score (0-6 points). The contents of serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) were measured by using ELISA, and the expression levels of p-JAK2/JAK2, p-STAT3/STAT3 and MMP-9 in knee cartilage tissue were detected using Western blot. Compared with the blank group, the Lequesne score, Mankin score, and the contents of serum IL-6, TNF-α and MMP-9, and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, and the expression level of MMP-9 protein in knee cartilage tissue were significantly increased in the model group (P<0.01). In comparison with the model group, the Lequesne score, Mankin score, contents of serum IL-6, TNF-α and MMP-9, and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, and the expression of MMP-9 protein in knee cartilage tissue were notably decreased in both the warm acupuncture and medication groups (P<0.01,P<0.05). The levels of Lequesne score, Mankin score, contents of serum IL-6, TNF-α and MMP-9, and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in knee cartilage tissue were significantly lower in the warm acupuncture group than in the medication group (P<0.01, P<0.05). No significant difference was found between the warm acupuncture and medication groups in the expression of MMP-9 protein (P>0.05). Outcomes of H.E. showed injury of the perichondrium of knee joint, obvious reduction of the cartilage matrix staining, cystic changes, clustered and disordered arrangement and severe pyknosis and necrosis of the surface cells with reduction of number of cells and increase of vacuoles in the model group, which was milder in both warm acupuncture and medication groups. Warm acupuncture can improve motor function and reduce cartilage injury in KOA rabbits, which may be related to its functions in inhibiting the secretion of pro-inflammatory factors and regulating JAK2/STAT3 signaling and downregulating MMP-9 expression in the cartilage tissue.

Diclofenac Ion Hydration: Experimental and Theoretical Search for Anion Pairs.

Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium.

Spatial resolution of drug crystallisation in the skin by X-ray micro-computed tomography

Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 – 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery.

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia.

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.

Diclofenac sodium aqueous systems at low concentrations: Interconnection between physicochemical properties and action on hydrobionts

Diclofenac sodium (DS) is a widely used nonsteroidal anti-inflammatory drug (NSAIDs). NSAIDs are poorly removed during standard wastewater treatment. The consequences of the presence of NSAIDs in rivers and lakes at 10−11–10−8 mol/L are not yet established; therefore, ecotoxicologists have focused their efforts on studying the effect of low-concentration NSAIDs on fish and hydrobionts, and also on predicting the potential risks to humans. Literature provides some information about the bioeffects of some NSAID solutions in low concentrations but there is no physicochemical explanation for these phenomena. Studying the physicochemical patterns of DS solutions in the low range of concentrations and establishing an interconnection between the solutions' physicochemical properties and bioeffects can provide a conceptually new and important source of information regarding the unknown effects of DS. The physicochemical properties and action of DS solutions on Ceriodaphnia affinis cladocerans, Paramecium caudatum infusoria, Chlorella vulgaris unicellular green algae, as well as on the growth of the roots of Triticum vulgare wheat seeds, were studied in the calculated concentration range of 1 × 10−3–1 × 10−18 mol/L. The relationship between these phenomena was established using the certified procedures for monitoring the toxicity of natural water and wastewater. It was shown for the first time that water solutions of DS are dispersed systems in which the dispersed phase undergoes a rearrangement with dilution, accompanied by changes in its size and properties, which affects the nonmonotonic dependences of the system's physicochemical properties and could cause nonmonotonic changes in action on hydrobionts in the low concentration range.

New diclofenac choline hydrate salt: Synthesis, characterization and solubility

A new choline hydrate salt of Diclofenac (DCF) was obtained using crystallization from a solution of DCF sodium and choline chloride in ethanol. The structure of the compound was determined by single-crystal X-ray diffraction. The DCF anions, choline cations and water molecules were arranged as a two-dimensional bridge structure connected through hydrogen bonds. The “choline-skeleton” in the crystal is systematically disordered, showing two propeller-like cage structures. The formation of a new compound was confirmed by the powder X-ray diffraction method. The thermal behavior of the salt was characterized by the DSC, DTA and HSM techniques. The compound solubility was measured by the shake-flask method at a temperature of 25 °C in water and buffer solutions with different pH that simulated physiological media. It has been established that the solubility of the synthesized salt is higher than that of DCF sodium in all the aqueous solutions used.

Facile synthesis of Fe3O4@MOF-100(Fe) magnetic microspheres for the adsorption of diclofenac sodium in aqueous solution.

In this research, the adsorptive removal of diclofenac sodium, one of the representative pharmaceuticals and personal care products, from aqueous solution using Fe3O4@MOF-100(Fe) magnetic microspheres was studied for the first time. The Fe3O4@MOF-100(Fe) microspheres exhibit strong magnetism and stability, which were observed as a core-shell structure. The maximum adsorption capacity of Fe3O4@MOF-100(Fe) for diclofenac sodium can reach 377.36mgL-1, which was higher than most of the adsorbents reported. The adsorption kinetics follows the pseudo-second-order kinetic equation. And the adsorption equilibrium of DCF can be described with Langmuir isotherm. In the cycle experiment, Fe3O4@MOF-100(Fe) material performed high adsorption efficiency for low-concentration diclofenac sodium solution, and the removal rate can still reach 80% after 5cycles of adsorption without desorption. The mechanisms including electrostatic interaction, H-bond interaction, and π-π interaction that coexisted in the adsorption processes would be of benefit to enhance the adsorption capacity. The Fe3O4@MOF-100(Fe) magnetic microspheres offer exciting opportunities for further application.

Qualitative and quantitative analysis of lateral diffusion of drugs in human skin

This study aimed to qualitatively and quantitatively analyze lateral diffusion of drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue dyes in skin was investigated using confocal laser microscopy, calcein imaging, and histology studies. In in vitro permeation studies, two linear microdialysis probes were inserted into the dermis of untreated, poly lacto-glycolic acid microneedle-treated, and ablative laser-treated skin such that one was in the center of the diffusion area and the other was parallel, at 8 mm from the central probe. Skin was mounted on Franz cells, sandwiched between donor containing diclofenac sodium solution and receptor containing phosphate buffered saline, pH 7.4. Qualitative techniques revealed faster lateral diffusion of the dyes in microneedle-treated skin than laser-treated skin. Rate of drug diffusion in the central probe in the microneedle-treated skin (11.8 ± 2.5 μg/h) was significantly higher than untreated and laser-treated skin (p < 0.05). Rate of lateral diffusion in untreated group (0.7 ± 0.1 μg/h) was significantly lower than microneedle and laser-treated skin (p < 0.05). Overall, in vitro microdialysis was demonstrated as a novel and valuable tool that can be employed for quantitative investigation of rate of vertical and lateral diffusion of drugs in intact and microporated skin.

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis

ABSTRACTOsteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Topical delivery of diclofenac into and across equine skin from a novel liquid diclofenac epolamine formulation.

The aim was to investigate diclofenac delivery into and across equine skin invitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass® (1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2mm. Skin samples were divided into two groups [Group 1: 1year old (n=2) and Group 2: 6-8years old (n=3)]. Cumulative permeation of diclofenac in Groups 1 and 2 after 24h using diclofenac sodium solution was 1.91±0.27 and 1.76±0.34μg/cm2 , respectively. The values for Surpass® and DIC-EP were 3.2±0.8/3.3±0.7μg/cm2 and 230±59/89.2±32.5μg/cm2 , respectively. Thus, diclofenac permeation from DIC-EP was significantly greater and appeared to show an age-dependent effect. Mathematical modelling showed that the DIC-EP formulation significantly increased diclofenac partitioning into the skin and a linear correlation was observed between steady-state flux and the partition parameter. Greater skin deposition of diclofenac was also observed with DIC-EP. These preliminary results suggest that the DIC-EP formulation may be effective in treating inflammatory conditions in horses.

Silk fibroin membranes for controlled release of drugs: incorporation method, chemical and morphological characteristics

Event Abstract Back to Event Silk fibroin membranes for controlled release of drugs: incorporation method, chemical and morphological characteristics Bruno Tomoda1, Marisa Beppu1, Mariana Agostini De Moraes1, 2 and Giovana M. Genevro1 1 University of Campinas, School of Chemical Engineering, Brazil 2 Federal University of São Paulo, Department of Exact and Earth Science, Brazil Introduction: Silk fibroin (SF) is a natural polymer present in the cocoons of silkworms, which has been studied in the biomaterials area[1],[2]. SF membranes have good water vapor and oxygen permeability, blood compatibility and improve collagen formation and fibroblast proliferation[3], which makes them a promising material for application as wound dressings. The aim of this work is to study the incorporation of a model drug in dense membranes of silk fibroin and evaluate the drug release kinetics, aiming application as high performance wound dressing. Materials and Methods: Silk fibroin solution was prepared from cocoons of Bombyx mori silkworm (provided by Bratac, Bastos/ SP/Brazil) according to previously published procedure[4],[5]. SF membranes were prepared by casting SF aqueous solution. Diclofenac sodium (DS), an anti-inflammatory and analgesic drug used worldwide, was chosen as drug model. Two different methods for DS solution (10 mg/mL) incorporation were studied: 1) Incorporation of DS solution directly in SF solution, prior to membrane preparation; 2) Incorporation of DS on SF membrane by adsorption. The membranes were characterized by FTIR and SEM-EDS. Drug release was performed in phosphate buffer saline (PBS) and in water. Samples were collected at fixed time intervals and analyzed by UV/vis spectroscopy, at 276 nm. Results and Discussion: FTIR results (Figure 1), show that pure SF membranes undergo conformation transition from random coil/α-helix to stable β-sheets when ethanol post-treatment is performed[5]. Interestingly, when DS solution is incorporated in SF solution, prior to membrane preparation, the same conformational transition is observed. For the incorporation method by adsorption, ethanol post-treatment of SF membranes was necessary, to avoid membrane degradation prior to the DS incorporation. Thus, ethanol post-treatment is a step of production that can be eliminated when DS solution incorporation method is performed. SEM micrographs (Figure 2) revealed that SF membranes prepared by DS incorporation in SF solution present globular structures of regular size and shape and uniformly distributed within the membranes. The process of globule formation was spontaneous and allowed the encapsulation of DS inside the globules, as confirmed by EDS mapping. On the contrary, when the adsorption method was performed, DS was found just on the surface of the membrane. Drug release results (Figure 3) demonstrate that DS has a faster initial release in water than in PBS. Moreover, DS was completely released in water, whereas in PBS just 70% of DS was released. This difference is related to DS solubility, which is higher in water than in PBS. The release equilibrium was reached after 100 minutes for both media. Conclusion: The method of DS solution incorporation directly in SF solution, prior to membrane preparation, was the most promising one. By this method SF underwent conformation transition to a more stable form, avoiding additional post-treatments. Furthermore, SF self-assembled into globular structures containing the DS encapsulated, which is usually desired for controlled release applications. SF membranes showed a fast initial release and equilibrium was reached after approximately 100 minutes of release. These results revealed an excellent drug incorporation method and confirm the potential application of SF membranes in wound dressings; however, further studies should be carried out in order to obtain a slow release kinetics. CNPq; FAPESP

Cationic guar gum polyelectrolyte complex micro particles

Aim: The aim of this study was to organize polyelectrolyte complex microparticles (PECMP) of cationic guar gum and xanthan gum. Materials and Methods: The complex formed was loaded with diclofenac sodium (DS) as a model drug. The prepared microparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning colorimetry (DSC), scanning electron microscopy (SEM), and evaluated for in vivo in vitro properties. Result: DSC and FT-IR studies were done to measure the formation of PEC and confirmed the absence of chemical interactions between drug and polymers. By SEM, the surface morphology was studied. Particle size ranged between 294 and 300 μm. The percentage of encapsulation efficiency of the microparticles was found to be 96.47%. In vitro release studies indicated that the drug release extended beyond 12 h. Kinetic analysis of dissolution data indicated that the drug release was by super case II mechanisms. Compared with DS solution, microparticles show low and prolonged drug release when subjected to in vivo pharmacokinetic evaluation in rabbits. Based on in vitro and in vivo studies, it was concluded that these micro particles provided oral controlled release of DS. Conclusion: The research findings obtained from the studies were found to be satisfactory. Hence, PECMP can be effectively used for preparation of sustained-release formulation. Key words: Cationic guar gum, micro particles, polyelectrolyte complex, xanthan gum.

Comparative removal of commercial diclofenac sodium by electro-oxidation on platinum anode and combined electro-oxidation and electrocoagulation on stainless steel anode

Aqueous solution of diclofenac sodium (DCFNa) from commercial analgesic pill was electro-oxidized on platinum and stainless steel (SS) anodes. On platinum anode, 66% degradation of the parent drug was achieved at pH 4.5 with a corresponding COD reduction of 49% for a specific charge of 4200 Coulombs/L. Degradation and COD reduction were less at higher pHs of 8.5 and 10.9. A number of intermediates were detected with some of them persisting at the end of the treatment. On SS anode, 84% drug removal and 80% COD decline were achieved for a specific charge of 4200 Coulombs/L at pH 10.9, owing to combined electro-oxidation and electrocoagulation. Contrary to platinum anode, here the drug removal and COD reduction were lesser at lower pHs of 8.5 and 4.5. Electrocoagulation was found to proceed with the organics directly forming complex with iron in the matrix of the SS anode with the iron oxidizing to Fe(III) at pH 10.9 and Fe(II) at pHs 8.5 and 4.5. Intermediates detected in residual liquid were much less in number and abundance.

Rapid spectrophotometric determination, characterization and anti-inflammatory efficacy evaluation of nanoencapsulated diclofenac sodium

This study was aimed to develop a simple and reproducible spectrophotometric method for the characterization of diclofenac sodium (DS) and to evaluate the efficacy of orally administered liposome encapsulated as well as free form DS in animal model. A simple, rapid and economical spectrophotometric analytical procedure with estimation in UV-visible region was performed on DS using dimethyl sulfoxide as solvent. Parameters such as time, temperature and types of solvent were studied for 20 μg/mL DS solution at 295 nm. All parameters and results of analysis were statistically validated. Liposome-encapsulated and free form DS samples were subjected to characterization study that includes entrapment efficacy determination and particle size analysis. Drug samples were further tested for their in vivo anti-inflammatory efficacy using histamine-induced paw edema test. Under optimized parameters, the Beer’s law is obeyed in range of 0.625-40 μg/mL at λmax 295 nm. A linear working range of 5-35 μg/mL with regression coefficient of 0.9978 was obtained by using seven triplicate analyses of drug samples at seven different concentrations. The limit of detection and limit of quantitation was 1.19 and 3.62 μg/mL, respectively. Result of characterization study showed that the optimum formulation, which has high entrapment efficacy of 87 %, homogenous in size (polydispersity index 0.27), stable and reproducible, were obtained by using the Pro-Lipo Duo with 10 h hydration time and 16 mg/g DS. The liposome encapsulated DS resulted in significant (P

Coaxial Electrospinning with Mixed Solvents: From Flat to Round Eudragit L100 Nanofibers for Better Colon‐Targeted Sustained Drug Release Profiles

A modified coaxial electrospinning process was developed for creating drug‐loaded composite nanofibers. Using a mixed solvent of ethanol and N,N‐dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS) and Eudragit L100 (EL100) could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one‐fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one‐fluid electrospinning, the DS‐loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon‐targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.

A Long-Term, Open-Label Study to Confirm the Safety of Topical Diclofenac Solution Containing Dimethyl Sulfoxide in the Treatment of the Osteoarthritic Knee

To assess the long-term safety of a topical solution of diclofenac sodium in a vehicle containing dimethyl sulfoxide (TDiclo), subjects with radiologically confirmed, symptomatic osteoarthritis of the knee(s) applied the clinical dose of TDiclo (40 drops, four times daily) to each painful knee for up to 52 weeks. Safety assessment included adverse events, skin irritation scores of the treated knee(s), ocular examinations, and routine laboratory tests. There were 793 subjects (mean age, 62.5 years) who applied TDiclo to one or both (72%) knees for an average of 204 days, including 463 subjects for 6 months and 144 for 1 year. The most frequent adverse events were at the application site with no increase in incidence with prolonged exposure: dry skin (25.3%), contact dermatitis without vesicles (13.0%) or with vesicles (9.5%). Skin irritation score was 0 (normal) in 61.0% of subjects, 0.5 (dryness or flaking) in 23.9%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Subject dropouts included 114 (14.4%) with an application site skin adverse event. Individual subject laboratory test shift to abnormal occurred for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few shifts (less than 0.3% per variable) were clinically significant. No increased risk of cardiovascular or cataract events was noted. This long-term study of TDiclo revealed a safety profile comparable to that shown in multiple, shorter, well-controlled, double-blind trials with the predominant adverse effect noted being an application site reaction.

Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation

Xanthan gum (XG), a trisaccharide branched polymer and poly vinyl alcohol (PVA), was used to develop pH-sensitive interpenetrating network (IPN) microspheres by emulsion cross-linking method in the presence of glutaraldehyde as a cross-linker to deliver model anti-inflammatory drug, diclofenac sodium (DS) to the intestine. Various formulations were prepared by changing the ratio of XG:PVA, extent of cross-linking in order to optimize the formulation variables on drug encapsulation efficiency, and release rate. Formation of interpenetrating network and the chemical stability of DS after penetration of microspheres was confirmed by Fourier Transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were done on the drug loaded microspheres which confirmed molecular dispersion of DS in the IPN. Microspheres formed were spherical with smooth surfaces, as evidenced by scanning electron microscopy (SEM), and mean particle size, as measured by laser light scattering technique ranged between 310.25–477.10 µm. Drug encapsulation of up to 82.94% was achieved as measured by UV method. Both equilibrium and dynamic swelling studies and in vitro release studies were performed in pH 1.2 and 6.8. Release data indicated a Fickian trend of drug release which depends on the extent of cross-linking and the ratio of XG:PVA present in the microsphere. When subjected to in vivo pharmacokinetic evaluation in rabbits, microparticles show slow and prolonged drug release when compared with DS solution. Based on the results of in vitro and in vivo studies it was concluded that these IPN microspheres provided oral controlled release of water-soluble DS.

Calorimetric studies of diclofenac sodium in aqueous solution of cyclodextrin and water-ethanol mixtures

The technique of solution calorimetry has been employed to study the interaction between diclofenac sodium and beta-cyclodextrin by determining the enthalpies of solution of the drug in water and in aqueous beta-cyclodextrin solution. Thermodynamic parameters characterizing the binding process such as enthalpy deltaH0, equilibrium constant K, free energy deltaG0 and entropy deltaS0 have been calculated to be 12.00 kJ mol(-1), 1670 dm3 mol(-1), -19.03kJ mol(-1) and 22.98 J K(-1) mol(-1), respectively. Enthalpies of solution of diclofenac sodium have also been determined in water-ethanol mixtures.