Release Rate Of Diclofenac Sodium Research Articles

Using Carbomer-Based Hydrogels for Control the Release Rate of Diclofenac Sodium: Preparation and In Vitro Evaluation.

The aim of the current research work was to prepare Car934-g-poly(acrylic acid) hydrogels by the free-radical polymerization technique. Various concentrations of carbopol, acrylic acid and ethylene glycol dimethacrylate were employed for the fabrication of Car934-g-poly(acrylic acid) hydrogels. Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC), Scanning electron microscope (SEM) and Powder X-ray diffractometry (PXRD) studies were performed to know the structural arrangement, thermal stability, physical appearance and amorphous network of developed hydrogels. FTIR analysis revealed that carbopol reacted with acrylic acid during the process of polymerization and confirmed the grafting of acrylic acid over the backbone of carbopol. TGA and DSC studies showed that developed hydrogels were thermally stable. Surface morphology was analyzed by SEM, which confirmed a porous network of hydrogels. PXRD analysis indicated that crystallinity of the drug was reduced by the amorphous network of hydrogels. Furthermore, swelling studies for all developed hydrogels were performed at both media, i.e., pH 1.2 and 7.4, and higher swelling was exhibited at pH 7.4. Sol–gel analysis was performed to evaluate the soluble unreacted part of the fabricated hydrogels. Similarly, an in-vitro study was conducted for all hydrogel formulations at both acidic (pH 1.2) and basic (pH 7.4) mediums, and a greater drug release was observed at pH 7.4. Different kinetics such as zero-order, first-order, the Higuchi model and the Korsmeyer–Peppas model were applied to know the mechanism of release order of drugs from the hydrogels.

Evaluation of a microemulsion-based gel formulation for topical drug delivery of diclofenac sodium

The aim of the current research was to investigate the release of diclofenac sodium, a poorly water-soluble drug from different formulations in vitro. A microemulsion (ME) was prepared using caprylocaproyl polyoxyl-8 glycerides, diethylene glycol monoethyl ether, and propylene glycol monolaurate. For enhancing the viscosity, carbopol was used to form an ME-based gel. The prepared formulations were characterized for physical appearance, droplet size, zeta potential, refractive index, percentage transmittance, heating–cooling cycles, phase separation, pH, conductivity, viscosity, drug content, staining solubility test, transmission electron microscopy and in vitro drug release using Franz diffusion cells. The mean droplets size for ME and ME-based gel-systems were 114.4 ± 0.472, and 178 ± 2.46 nm respectively, whereas the zeta potential values were −33.3 ± 0.64 mV for the former and −33.0 ± 0.40 mV for the latter. No significant variations in the pH nor physical appearance alterations were observed while stability tests were performed. Further, TEM images for drug-loaded ME and the gel exhibited nano-droplets that were spherical in shape. The release rate of diclofenac sodium formulated as ME or as ME gel had the highest release values (76.67 ± 8.63%) and (69.28 ± 7.14%) after 6 h respectively. This was statistically significant (p < 0.0001) compared to the control and different marketed formulations or compounded preparations. The ME-based gel had a higher viscosity suitable for topical administration without dripping. The in vitro result suggested that ME systems are powerful topical vehicles for enhanced penetration of diclofenac sodium.

Formulation and evaluation of tamarind seed polysaccharide matrix tablet

Objective: The objective of using natural polymer was to modify the release rate of Diclofenac sodium from matrix tablet. The matrix forming agent like Tamarind seed Polysaccharide show sustained release property in tablet which is obtained naturally from fruit of Tamarindus indica L. belonging to Family Leguminosae. Methods: The sustained release matrix tablet of Diclofenac sodium were prepared by wet granulation technique using varying concentration of hydrophilic polymer i.e. TSP. Results: OF1 and OF2 both are optimized batch. The in vitro dissolution study was carried out for optimized as well as marketed formulation (Voveran- SR). Both the optimized batchesat 10 h were found to be 90.27% and 90.18%, respectively. Conclusions: Tamarind seed polysaccharide can be employed in dosage form to sustain the drug release. Tablet formulated with various concentrations of Tamarind seed polysaccharide (TSP) gives release up to 10 h and more. OF1 and OF2 both formulations give comparable release with marketed formulation. From the present work it can be conclude that, the objectives which were set at the beginning of the study got fulfilled.

Development of an osmotic pump system for controlled delivery of diclofenac sodium

Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol–gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca 2+, reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8 h more compared with the pristine SA hydrogel beads.

Development and Evaluation of Enteric Coated Tablet Containing Diclofenac Sodium

The influence of various polymers on the release rate of Diclofenac Sodium from enteric coated tablets was investigated in an attempt to formulate a delayed release solid dosage forms. Prepared the conventional diclofenac sodium tablets by wet granulation method (non-aqueous) using granulating fluid (isopropyl alcohol). Developed the aqueous coating formula using shacryl and non-aqueous coating formula using HPMCP and optimized the best aqueous coating formula. Coating was performed in a mini coating pan at 107 rpm using low-pressure air atomized liquid spray techniques. Comparative dissolution, disintegration and antiulcer studies were performed on the best products and marketed products. The Comparative antiulcer studies were performed on wister albino rats using conventional, dummy and enteric-coated tablets.

Investigation of the Effect of Different Flow-Through Cell Designs on the Release of Diclofenac Sodium SR Tablets

This study was proposed to evaluate the effect of different cell designs and hydrodynamic conditions of the flow-through cell (FTC), USP dissolution Apparatus 4, on the release rate of a sustained-release product. Sustained-release (SR) diclofenac sodium (DS), 100 mg/tablet, was selected for this study. Different cell sizes and types, the flow rate of dissolution medium, and the tablet position within the FTC were considered. Results revealed that some of these variables affect the release rate of DS. It was obvious that the turbulent flow of the dissolution medium resulted in a higher DS release rate compared with the laminar flow. In addition, the results show that the drug release rate decreased when the tablet was buried in the glass beads compared with the unburied tablet. On the other hand, variables such as cell size (12-mm and 22.6-mm diameter), flow rates (8 and 16 mL/min), and presence of a tablet holder had a negligible role in drug release rate.

Comparison of different water/oil microemulsions containing diclofenac sodium: Preparation, characterization, release rate, and skin irritation studies

The aim of the present study was to make a comparison of the in vitro release rate of diclofenac sodium (DS) from microemulsion (M) vehicles containing soybean oil, nonionic surfactants (Brij 58 and Span 80), and different alcohols (ethanol [E], isopropyl alcohol [I], and propanol [P]) as cosurfactant. The optimum surfactant:cosurfactant (S:CoS) weight ratios and microemulsion areas were detected by the aid of phase diagrams. Three microemulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity. According to the release rate of DS, M prepared with P showed the significantly highest flux value (0.059 +/- 0.018 mg/cm(2)/h) among all formulations (P < .05). The conductivity results showed that DS-loaded microemulsions have higher conductivity values (18.8-20.2 microsiemens/cm) than unloaded formulations (16.9-17.9 microsiemens/cm), and loading DS into the formulation had no negative effect on system stability. Moreover, viscosity measurements were examined as a function of shear rate, and Newtonian fluid characterization was observed for each microemulsion system. All formulations had appropriate observed pH values varying from 6.70 to 6.85 for topical application. A skin irritation study was performed with microemulsions on human volunteers, and no visible reaction was observed with any of the formulations. In conclusion, M prepared with P may be a more appropriate formulation than the other 2 formulations studied as drug carrier for topical application.

Xanthan–alginate composite gel beads: Molecular interaction and in vitro characterization

Xanthan gum (XG), a trisaccharide branched polymer, was applied to reinforce calcium alginate beads in this study. Composite beads consisting of XG and sodium alginate (SA) were prepared using ionotropic gelation method. Diclofenac calcium-alginate (DCA) beads incorporated with different amounts of XG were produced as well. Molecular interaction between SA and XG in the composite beads and the XG–DCA beads was investigated using FTIR spectroscopy. Physical properties of the XG–DCA beads such as entrapment efficiency of diclofenac sodium (DS), thermal property, water uptake, swelling and DS release in various media were examined. XG could form intermolecular hydrogen bonding with SA in the composite beads with or without DS. Differential scanning calorimetric study indicated that XG did not affect thermal property of the DCA beads. The DS entrapment efficiency of the DCA beads increased with increasing amount of XG added. The XG–DCA beads showed higher water uptake and swelling in pH 6.8 phosphate buffer and distilled water than the DCA beads. A longer lag time and a higher DS release rate of the XG–DCA beads in pH 6.8 phosphate buffer were found. In contrast, the 0.3%XG–DCA beads could retard the drug release in distilled water because interaction between XG and SA gave higher tortuosity of the bead matrix. However, higher content of XG in the DCA beads increased the release rate of DS. This can be attributed to erosion of small aggregates of XG on the surface of the DCA beads. This finding suggested that XG could modulate physicochemical properties and drug release of the DCA beads, which based on the existence of molecular interaction between XG and SA.

Electrospun Multifunctional Diclofenac Sodium Releasing Nanoscaffold

Electrospinning is a method utilized to produce nano-scale fibers for tissue engineering applications. A variety of cells are attracted by nano scale surfaces and structures probably due to the similarity of their natural environment scale. In this study, diclofenac sodium (DS) releasing nanofibers were manufactured via electrospinning process. Poly(95 epsilon-capro/5 D,L-lactide) was dissolved into acetic acid to form a 20% w/v solution. 2% w/w of DS was then added into the polymer solution and stirred homogenously. About 1 g of polymer/drug solution was spun onto the collector under electrostatic conditions. The distance between needle tip and sample collector was arranged to 10 cm and applied electric field was 2 kV/cm. Release rate of DS was measured by using UV/VIS spectrophotometer. Resulted highly porous nanofiber scaffold was about 2 mm thick and the diameter of nanofibers was approximately 130 nm. Structure included in also spheres with approximately diameter of 3.30 microm. About 45% of DS was released during the first 24 hours and after that the release decreased to almost zero value. After 35 days release rate increased. This study revealed that manufacturing of highly porous DS releasing nanoscaffold by electrospinning process is feasible. Having fast DS release rate nanofibrous scaffold made of poly(95 epsilon-capro/5 D,L-lactide) can be of benefit for applications where immediate control of tissue reaction is needed.

Modulation of drug release from glyceryl palmitostearate–alginate beads via heat treatment

Diclofenac calcium alginate (DCA) beads containing glyceryl palmitostearate (GPS) were prepared by ionotropic gelation method. The effect of GPS amount and heat treatment on characteristics of the DCA beads was investigated. Incorporation of GPS into the DCA beads increased particle size and entrapment efficiency of diclofenac sodium (DS), but decreased water uptake in distilled water, and DS release rate. The heat treatment caused the DCA beads to be irregular shape particles and to possess higher water uptake. A slower release rate of DS in distilled water was found because of interaction of DS and alginate polymer matrix, and a restriction of water sorption into the inside region of the beads, which caused by the shrinkage of the beads after heating. However, the heat treatment did not affect particle shape and water uptake in distilled water of the 3%GPS–DCA beads. Differential scanning calorimetric study showed that GPS in the DCA beads was resolidified to different polymorph after cooling. Furthermore, the micro-Raman spectra indicated the existence of DS in the GPS matrix particles in the beads due to the partition of DS into the melted GPS during heat treatment. This led to a decrease in release rate of DS in pH 6.8 phosphate buffer and a change in DS release pattern in distilled water. Thus, not only the calcium alginate matrix, but also the resolidified GPS matrix in the alginate beads controlled the DS release from the 3%GPS–DCA beads with heat treatment.

The Influence of Thermal Treatment on the Release Behavior of Diclofenac Sodium from Acrylic Matrices

The objective of this work was to investigate the effect of thermal treating on the release rate of diclofenac sodium from Eudragit RS and Eudragit RL matrices. Eudragit RS and RL are nonswelling polymers that have a low glass transition (Tg) temperature. The matrices were thermally treated at different temperatures (40, 50, 60, and 70°C) for different periods of times (2, 5, and 24 h). The results showed that thermal treating at temperatures less than the Tg of the polymer has no effect on the release of the drug, whereas heat-treating at temperatures higher than the Tg decreases the release rate of diclofenac sodium from matrices. It was shown that the duration of heat treatment was also an important factor in controlling the release rate of diclofenac sodium from Eudragit matrices. The results showed that an increase in the duration of heat treatment from 2 h to 24 h resulted in a reduction in the release rate of the drug. Scanning electron microscopy of the cross section of the tablet before and after heat treating showed that the tablets were deformed and fused into a continuous and homogeneous structure after heat treating. Thermally treated tablets demonstrated fewer surface defects than did nonthermally treated tablets. These structural changes in the tablet compacts resulted in a matrix structure that decreased the release rate of the diclofenac sodium from Eudragit matrices.

Swellable Matrices for the Controlled‐Release of Diclofenac Sodium: Formulation and In Vitro Studies

Oral administration has been the most usual and convenient employed route of drug delivery systems. Particularly, oral sustained‐release systems for the delivery of drugs by a process of continuous swelling of the polymeric carrier have been investigated. Thus, the goal of this study was to evaluate the effects of hydroxypropyl methylcellulose (HPMC) and carboxypolymer (Carbopol® 934) on the release behavior of diclofenac sodium (DS) from a swellable matrix tablet system. Nine different DS controlled‐released tablets were compressed by using the wet‐granulation technology. The influence of the polymer content, the polymer ratio, the polymeric swelling behavior, and the pH changes on the release rate of DS was investigated. There was no significant difference in drug release when total polymer concentration was 10%. When the tablets were formulated having 20% or 30% of HPMC/carbomer, it was observed that a more rapid release of DS occurred as the carboxypolymer ratio within the matrices increased. In agreement with previous results, the dissolution studies demonstrated that the combination of these two polymeric matrix formers resulted in near zero‐order release rate of DS. The DS release from all these matrix tablets was pH dependent, being markedly reduced at lower pH, and could be attributed to the poor solubility of DS at this pH value. In HCl 0.1 N solution, HPMC controlled drug release because the carbomer has a low solubility at this pH. As the pH increased, the carbomer became ionized, being able to interact with HPMC to control the drug release.

Drug release behavior of beads and microgranules of chitosan

Beads and microgranules carriers have important potential applications for the administration of therapeutic molecules. A novel approach for the preparation of chitosan beads and microgranules is presented. The present work is an investigation of the in vitro release kinetics of diclofenac sodium (DFS) from chitosan beads and microgranules. The in vitro release profiles of DFS from chitosan beads and microgranules are monitored using Shimadzu 1601 UV–VIS spectrophotometer. Drug release behavior of beads and microgranules has been compared. The release rate of DFS from the beads has been found to be slower in comparison to the microgranules. It may also be noted that the percent and amount of the drug release were much higher in acidic solution than in basic solution, probably due to the swelling properties of the matrix at acidic pH.

DEVELOPMENT AND EVALUATION OF A PROLONGED-RELEASE MATRIX TABLETS OF DICLOFENAC SODIUM RESINATE

The preparation of a potential prolonged-release matrix tablets (IER-tablets) containing diclofenac sodium – anion exchange resin (Dowex I-X8.Cl-) complexes has been performed by direct compression of the drug-resin complex (drug resinate) with various release-regulating excipients (Avicel PH 101, lactose, sodium carboxymethylcellulose, and compritol). All the formulations produced tablets with good mechanical properties. The in-vitro release rate of diclofenac sodium from the drug-resin complex samples with different loaded concentrations and from the prepared IER-tablets (Kh = 0.92-5.52 mg/min-0.5) was determined using a rotating paddle dissolution apparatus. The results obtained showed that drug release from these formulations was slower than from the tabletted diclofenac sodium alone (Kh = 6.55-15.10 mg.min-0.5) or a commercial sustained-release tablet formulation of diclofenac sodium (Kh = 8.23 mg.min-0.5) and that IER-tablets containing sodium carboxymethylcellulose or compritol exhibited the lowest release rates (Kh = 0.92 and 1.27 mg/min-0.5, respectively). The kinetics of the drug release from resinate was evaluated on the basis of the mass low. In most cases, the profiles for both the effect of drug/resin ratio and sodium ion concentration upon drug release from the resonates exhibited two release rate processes: rapid release during the initial period, followed by a decreasing release rate, suggesting a particle diffusion release process. The release rate data of the tablets were investigated by using zero-order and the matrix-diffusion-controlled kinetics. The calculated exponential release exponents (n-values) revealed that release behaviour of all IER-tablets was a Fickian-diffusion kinetics (i.e., The Higuchi-linear square root of time relationship), confirming that a matrix diffusion-controlled mechanism was operative. To evaluate the feasibility of the drug resinate tablet system, the optimum IER-tablet formulations, drug resonates, sustained-release commercial tablet product and plain drug were examined for their ulcerogenic activity in rabbits. The results proved the superiority of the drug resinate and IER-tablets containing Avicel PH 101 over the plain drug, commercial product or IER-tablets containing compritol or sodium carboxymethylcellulose. Overall, this study demonstrated the significance of using ionic complex systems in offering a simple gastro-protected tablets and showed the characteristics of the matrix materials and their influence on the drug activity as well as tablet performance in-vivo.

Effect of coating of aluminum carboxymethylcellulose beads on the release and bioavailability of diclofenac sodium

The production of spheres loaded with diclofenac sodium by the cross linking technique was achieved. The hydrophilic polymer sodium carboxymethylcellulose (Na-CMC) which gels in the presence of a cross linking agent, aluminum chloride (AlCl3), was used as a matrix forming agent for the bead production. To obtain a regular and uniform rate of drug release, the produced beads were coated with sodium alginate to increase the pathway of the diffused medium. Two processing variables were studied, the flocculating agent concentration (20, 40 and 60% w/v) and different coating times (15, 30 and 60 min). The results show that the higher concentrations of aluminum chloride (40 and 60% w/v) produced more uniform and rounded beads than that prepared using 20% w/v salt. The particle size of the core beads decreased insignificantly (P > 0.05) as the flocculating agent concentration increased. The coating time did not affect the particle size of the coated beads within the same concentration of aluminum chloride. The dissolution studies showed that the release rate of diclofenac sodium from the core beads increased with the increase of AlCl3 concentration and that the rate of drug release was markedly reduced after the coating of the core beads with Na-alginate. The results also show a linear relationship for drug release over a 4–5 h period from the core beads where it showed a longer straight line relationship (7 h) for the coated beads. The coating of the Al-CMC beads, prepared using 60% w/v AlCl3 · 6H2O, with 2% w/v aqueous solution of Na-alginate resulted in a significant (P < 0.05) sustaining action of the Al-CMC beads as indicated by the shift in Tmax from 1.7 ± 0.84 to 3 ± 0.71 h and the prolongation of the MRT from 7.86 ± 0.54 to 10.82 ± 1.33 h. The Cmax increased significantly from 5.43 ± 2.91 to 11.66 ± 6.18 μg/ml while the AUC0 → 24 increased insignificantly (P > 0.05) from 39.82 ± 26.61 to 57.92 ± 25.58 μg · h/ml resulting in a relative bioavailability of 145.45% relative to Al-CMC beads.

Studies on Controlled-Release Formulations of Diclofenac Sodium

The effects of various polymers on the release of diclofenac sodium from their matrices have been evaluated. In vitro release profiles of diclofenac sodium from ethylcellulose and hydroxypropylmethylcellulose (HPMC) K4M matrices showed that decreasing the concentration of ethylcellulose and increasing the concentration of HPMC K4M resulted in an increase in the release rate of diclofenac sodium. An increase in the amount of lactose in matrix resulted in an increase in the release rate of diclofenac sodium. It is suggested that the use of ethylcellulose or Precirol containing relatively large percentage concentrations of lactose in matrices will not provide zero-order release of diclofenac sodium from matrices. The best-fit release kinetics with the highest correlation coefficients was achieved with the Higuchi's plot followed by the zero-order. A straight line relationship was established bemeen the T50% and the ratio of HPMC K4M to diclofenac sodium.

Preparation and Characterization of Polyvinyl Acetate (Kollidon® SR) Microspheres Containing Diclofenac Sodium I: Effect of Stirring Rate and Total Solid Content

Microspheres were prepared by W/O emulsification solvent evaporation technique where Diclofenac Sodium (DS) and Kollidon® SR (KSR) were used as model drug and polymer respectively. Light liquid paraffin (LLP) was used as oil phase and 1% (w/w of the continuum) of span 60 was used for emulsification. Microspheres were prepared using different stirring rate (1500, 2000, 2500, 3000 rpm) and different total solid content of the system (0.08%, 0.16%, 0.24% w/w of the continuum). Microsphere morphology was examined with the help of Scanning Electron Microscope (SEM) and particle size distribution was analyzed by Mastersizer 2000. Larger microspheres were obtained with decreasing stirring rate. Increase in solid content of the system also increased microsphere size. Drug loading was also found to be affected due to these preparative variables. In vitro dissolution study was performed in a USP XXX paddle apparatus (type 2). Dissolution media was buffer of pH 7.2, paddle speed was 50 rpm and dissolution temperature was maintained at 37 ± 0.5°C. Release of DS from KSR microspheres was found to follow higuchi mechanism. DS release was increased with increased stirring rate. But increased solid content of the system resulted in reduced release of DS. Normalized release rate of DS was also found to be affected by these preparative variables. Release rates were found increased with increased stirring rate whereas rates were found decreased with increased solid content of the system. Key words: Kollidon® SR; Diclofenac Sodium; Microsphere; Solvent evaporation technique. 10.3329/dujps.v8i2.6024 Dhaka Univ. J. Pharm. Sci. 8(2): 111-116, 2009 (December)