Release Of Diclofenac Sodium Research Articles

Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems

Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked – (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA.

Preparation of Liquisolid Compacts of Diclofenac Sodium and Evaluation of their Release Enahancing and Retarding Properties

Numerous methods have been applied to improve drug release of pharmaceuticals, among which the liquisolid technology is a recent and most promising approach. With this technique liquid formulations such as solutions or suspensions of poorly soluble drugs in a non-volatile liquid vehicle are converted into acceptably flowing and compressible powders of desirable release profile. In this study, several liquisolid tablets of diclofenac sodium (DS) containing various concentrations of the liquid medication (52, 60 and 70% w/w) were prepared. The ratio of carrier to coating powder material was varied to be 10, 20, and 30. Propylene glycol (PG), polyethylene glycol 400 (PEG 400) and polysorbate 80 were used as non-volatile solvents. The prepared liquisolid compacts were then evaluated for their drug release profiles. The liquisolid compacts demonstrated considerably higher dissolution rates than marketed tablets. It was also shown that the fraction of molecularly dispersed drug in the liquid medication of the liquisolid compacts was directly proportional to the dissolution rate. Liquisolid compacts prepared to sustain the release of DS showed comparable release profile with the marketed preparation. It was revealed that polysorbate 80 and Eudragit® RL have important role in sustaining the release of the drug from liquisolid matrices. This study showed that liquisolid technology is a flexible approach to enhance or retard the release of DS from compressed formulations.Keywords: Diclofenac Sodium, Liquisolid Compact, Drug Release, Dissolution Rate, Sustained Release

Preparation and Evaluation of Diclofenac Sodium Tablet Coated with Polyelectrolyte Multilayer Film Using Hypromellose Acetate Succinate and Polymethacrylates for pH-Dependent, Modified Release Drug Delivery.

Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract.

An electro-conductive fluid as a responsive implant for the controlled stimuli-release of diclofenac sodium

The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro-liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug-free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N ± 0.33 N/mm2; resilience = 10.91 ± 0.11%), thermal properties (Tg ≈ 70 °C; Tc ≈ 200 °C) and homogeneous morphology. “ON–OFF” pursatile gradual drug release (37–94% from t30 min−t180 min) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant.

Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery

Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94–60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

Surface modified natural zeolite as a carrier for sustained diclofenac release: A preliminary feasibility study

In view of zeolite potentiality as a carrier for sustained drug release, a clinoptilolite-rich rock from California (CLI_CA) was superficially modified with cetylpyridinium chloride and loaded with diclofenac sodium (DS). The obtained surface modified natural zeolites (SMNZ) were characterized by confocal scanning laser microscopy (CLSM), powder X-ray diffraction (XRPD) and laser light scattering (LS). Their flowability properties, drug adsorption and in vitro release kinetics in simulated intestinal fluid (SIF) were also investigated.CLI_CA is a Na- and K-rich clinoptilolite with a cationic exchange ability that fits well with its zeolite content (clinoptilolite=80wt%); the external cationic exchange capacity is independent of the cationic surfactant used. LS and CLSM analyses have shown a wide distribution of volume diameters of SMNZ particles that, along with their irregular shape, make them cohesive with scarce flow properties. CLSM observation has revealed the localization of different molecules in/on SMNZ by virtue of their chemical nature. In particular, cationic and polar probes prevalently localize in SMNZ bulk, whereas anionic probes preferentially arrange themselves on SMNZ surface and the loading of a nonpolar molecule in/on SMNZ is discouraged. The adsorption rate of DS onto SMNZ was shown by different kinetic models highlighting the fact that DS adsorption is a pseudo-second order reaction and that the diffusion through the boundary layer is the rate-controlling step of the process. DS release in an ionic medium, such as SIF, can be sustained for about 5h through a mechanism prevalently governed by anionic exchange with a rapid final phase.

Comparative Study of Polycomplexes Based on Carbopol® and Oppositely Charged Polyelectrolytes as a New Oral Drug Delivery System

We report here a comparative study of the release of model drug diclofenac sodium from samples of interpolyelectrolyte complexes (IPEC) in in vitro conditions on a rotating basket apparatus and in vivo in experiments in rabbits. The study IPEC were prepared using different grades of Carbopol® polymer (C71g, C2020) and Noveon® AA-1 and oppositely charged polyelectrolytes – Eudragit® EPO or the natural polysaccharide low-viscosity chitosan. These studies demonstrated the potential for IPEC samples based on Carbopol® as a new modified-release drug delivery system. At the same time, assessment of bioadhesive properties provided evidence of the potential for using IPEC based on C2020/EPO as a mucoadhesive carrier.

Synthesis, characterization, and in vitro drug release study of 3‐arm poly‐β‐alanine

ABSTRACTSynthesis of three arms star‐shaped poly‐β‐alanine (3‐b‐ala) based on tri(prop‐2‐yn‐1‐yl) benzene‐1,3,5‐tricarboxylate (TBT) and azido terminated poly‐β‐alanine (N3‐P‐ala) was performed using click reaction. TBT was synthesized by nucleophilic substitution reaction between propargyl alcohol and 1,3,5‐benzenetricarbonyltrichloride. For the first time, N3‐P‐ala was synthesized through anionic polymerization of acrylamide using sodium azide as an initiator. TBT was characterized by FT‐IR and 1HNMR. N3‐p‐ala was characterized by FT‐IR, GPC, and 1HNMR and 3‐b‐ala was characterized by FT‐IR, GPC, 1HNMR, TGA, and XRD. The synthesized 3‐b‐ala was used for drug loading and releasing studies. Polymer loaded drug (3‐b‐ala‐D) hybrid was used in in vitro studies of drug (Diclofenac sodium) release in phosphate buffer solution (PBS) at 37 ± 0.5°C and pH 7.4. The drug loading and releasing studies were analyzed by UV‐visible spectrophotometer. 3‐b‐ala‐D was examined by AFM to analyze the surface morphology and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42124.

Сравнительное исследование поликомплексов на основе Carbopol<sup>®</sup> и противоположно заряженных полиэлектролитов как новых систем пероральной доставки

Проведено сравнительное исследование высвобождения модельного лекарственного вещества диклофенака натрия из образцов интерполиэлектролитных комплексов (ИПЭК) в условиях in vitro на приборе «вращающаяся корзинка» и in vivo в экспериментах на кроликах. Исследуемые ИПЭК были получены на основе различных марок полимеров Carbopol® (C71g, C2020) и Noveon® AA-1 и противоположно заряженных полиэлектролитов Eudragit® EPO или природного полисахарида хитозана низковязкого. Проведенные исследования доказывают перспективность образцов ИПЭК на основе Carbopol® как новых систем доставки с модифицированным высвобождением лекарственных веществ. В то же время проведённая оценка биоадгезивных свойств свидетельствует о перспективности использования ИПЭК на основе C2020/EPO в качестве мукоадгезивного носителя.

PH-sensitive starch-g-poly(acrylic acid)/sodium alginate hydrogels for controlled release of diclofenac sodium

The pH-sensitive starch-g-poly(acrylic acid)/sodium alginate (St-g-PAA/SA) hydrogel beads for the controlled release of diclofenac sodium(DS) were prepared simply by crosslinking SA using calcium ions under the existence of the St-g-PAA superabsorbent. The St-g-PAA/SA-DS hydrogel beads were characterized by IR and scanning electron microscopy. The effects of weight ratio of St-g-PAA to SA and pH on the swelling behaviors of the hydrogel beads in pH 7.4 phosphate buffer solution were investigated. In addition, the effects of weight ratio of St-g-PAA to SA and the concentration of SA solution on the entrapment efficiency (EE) for DS and the cumulative release of DS were studied in detail. The St-g-PAA/SA-DS hydrogel beads are pH-sensitive with an interpenetrated polymer network. The introduced St-g-PAA superabsorbent has great influence on the swelling behavior and the cumulative release of DS. The pristine SA-DS hydrogel beads disintegrated in pH 7.4 phosphate buffer solution in 3 h, whereas the disintegration of SA-DS beads was delayed or avoided by introducing a proper amount of the St-g-PAA superabsorbent. Also, the burst release of DS was successfully overcome by the introduced St-g-PAA superabsorbent. A weight ratio of St-g-PAA to SA of 1:9 and an SA concentration of 4 wt % are very helpful for the sustained release of DS.

Development and optimization of interpenetrating network beads of delonix regia gum and sodium alginate using response surface methodology

The aim of present investigation was to develop and optimize sustained release interpenetrating network (IPN) beads of delonix regia seed polysaccharide (DRG) and sodium alginate using response surface methodology. Diclofenac sodium (DS) was chosen as model drug. A central composite design was used to study and optimize the effect of independent variables (A: sodium alginate:DRG ratio and B: calcium chloride concentration) on drug encapsulation efficiency (DEE, %) and drug release in 8h (R8h, %). Total thirteen batches of DRG-alginate IPN beads were prepared by ionotropic gelation method using calcium chloride as a cross-linking agent. The DEE (%) of the beads was found in the range 32.79-56.54%. Swelling of beads was high in phosphate buffer (pH 6.8) whereas, less in 0.1 N HCl (pH 1.2). The beads exhibited sustained release of DS for 8h (65.6±0.98 - 99.9±1.87%) and followed Higuchi model demonstrating non-fickian diffusion mechanism. The observed responses of the optimized batch were similar to the predicted values determined by Design Expert (V.7.0, Stat-Ease Inc, USA) software. The optimized DRG-alginate IPN beads may show good encapsulation of water soluble drugs followed by their sustained release for 8h which might be advantageous in terms of advanced patient compliance with reduced dosing interval.

Pectin-Chitosan Multilayer Coated Microbeads of Diclofenac Sodium Prepared by Layer-by-Layer Technique

The main objective of this study was to fabricate biopolymer-based microbeads, providing enteric properties and controlled release of diclofenac sodium, using layer-by-layer technique. The calcium pectinate microbeads have been designed and coated with chitosan and pectin multilayers. Drug release was performed in simulate gastric fluid (pH 1.2) for 2 hours, followed by pH 6.8 buffer for 8 hours. The effects of chitosan concentration, number of layer and drying technique on drug release were investigated. The results showed that the calcium pectinate microbeads could be simply prepared by ionotropic gelation and then coated with chitosan and pectin solutions using layer-by-layer procedure. The diameter of the microbeads ranged from 800 to 1000 μm for air-dried samples and from 1 to 2 mm for freeze-dried samples. The freeze-dried microbeads had a rough surface and many pores inside, as observed by SEM. The microbeads coated with 4% chitosan/4% pectin revealed a slower drug release than those coated with 1% chitosan/4% pectin and demonstrated a controlled release pattern. Moreover, different drying techniques and numbers of layer also influenced drug release behavior of the prepared microbeads.

Investigation of localized delivery of diclofenac sodium from poly(D,L-lactic acid-co-glycolic acid)/poly(ethylene glycol) scaffolds using an in vitro osteoblast inflammation model.

Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications.

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.

Implantable micro-chip for controlled delivery of diclofenac sodium

We prepared an implantable micro-chip enabled for controlled delivery of diclofenac sodium (DS). The micro-chip was made of poly(methyl methacrylate), where a pair of micro-channels and micro-wells was embedded to serve as a drug diffusion barrier and a reservoir, respectively. For this purpose, the micro-channel and micro-well were filled with a water-soluble polymer, polyethylene glycol and a fine powder of DS, respectively. To modulate the drug release profile, we varied both the cross-sectional area and length of the micro-channels. Thus, the average rate and onset time of drug release could be varied from 0.32%/day to 3.68%/day and from day 0.5 to day 8, respectively, as the cross-sectional area to length ratio (i.e., A/L) of the micro-channels increased from 0.0026mm to 0.0280mm. To achieve both almost immediate onset and zero-order release of DS, we also prepared a micro-chip embedded with multiple pairs of the micro-wells and the micro-channels of different dimensions. In this work, a single micro-chip equipped with the micro-channels with A/Ls of 0.0280mm, 0.0217mm and 0.0108mm exhibited almost zero-order drug release for 31days (R2>0.996) after the release onset on day 0.5. When the resulting micro-chip was implanted in living rats, the drug concentration in the blood could be maintained at 148ng/ml–225ng/ml for the first 23days while showing good biocompatibility.

Confirmatory evidence other than 1hnmr spectroscopic technique for complex formation of diclofenac sodium with go-ghrita

Present investigation showing confirmatory evidence for complex formation of Diclofenac sodium (Dic) with Go-Ghrita (GG) by various sophisticated techniques like FT-IR, In-vitro release study, DSC, X-ray diffraction and SEM other than 1 NMR (which is reported earlier). Diclofenac sodium binary mixture in (1:0.5), (1:1), (1:2), (1:3) w/w proportions were prepared by adding to molten Go-Ghrita kept over a water bath at 65-70 o C with continuous stirring. Organoleptic and Physico-chemical properties of GG (procured from Magan Sangrahalaya, Wardha) were as per the specifications given in Ayurvedic Pharmacopoeia (AP) and Indian Pharmacopoeia (IP). All proportions were subjected for FT-IR and in-vitro release behaviour (SGF, P H 1.2 for 2 Hrs and SIF, P H 6.8 for 7 Hrs) and on basis of it, optimized (1:1) w/w proportions were further analyzed and characterized for Differential Scanning Calorimetry, X-ray diffraction and Scanning Electron Microscopy. Carbonyl stretching of benzene acetic acid group to slight higher frequency 9.23 % cm -1 (increase) and (–C=O) linked (-OH) band stretching to slight lower frequency 0.57 cm -1 (decrease) shown in FT-IR spectra, supported by in-vitro release of Diclofenac sodium 99.13±0.31% of (1:1) w/w in sustenance form than remaining. Retention of peaks with lesser intensity in binary mixture of drug with GG, revealed crystalline as well as non-crystalline (amorphous) nature in X-RD, Slight lowering of 17.6 0 C Tm and enthalpy change of 8.51 % (loss) in DSC, and entrapment of Diclofenac sodium crystals in Dic-GG binary mixture shown in SEM photographs, reflecting possible evidence for the formation of inclusion type complex between Diclofenac sodium and GG.

Inorganically modified diatomite as a potential prolonged-release drug carrier

Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM–EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice.High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer–Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process.

Superhydrophobic Gated Polyorganosilanes/Halloysite Nanocontainers for Sustained Drug Release

Inspired by the water repellency of the lotus leaf, superhydrophobic gated nanocontainers are fabricated by using halloysite nanotubes (HNTs) as the nanocontainers and polyorganosilanes (POS) as the molecular gates for sustained release of diclofenac sodium (DS). The nanocontainers are prepared by loading DS into the lumen of HNTs, and then modified by co‐condensation of hexadecyltriethoxylsilane and tetraethoxysilane. The nanocontainers are characterized with transmission electron microscopy, energy dispersive X‐ray analysis and FTIR, etc. The wetting behaviors of the nanocontainers and release behaviors of DS are also studied. DS molecules are loaded in the lumen of HNTs and POS is covalently bonded on the surface of HNTs‐DS. Wettability of the nanocontainers is controllable simply by the POS content. The nanocontainers show excellent superhydrophobicity with a water contact angle of 156.9° and a water shedding angle of 3°. The release of DS molecules is controlled by a new way, the air cushion between the superhydrophobic nanocontainers and the phosphate buffer solution (PBS). The DS molecules could only release from the limited place where the nanocontainers contact with PBS when the PBS is in the Cassie‐Baxter state on the surface of the nanocontainers.

Diclofenac Sodium Adsorption onto Montmorillonite: Adsorption Equilibrium Studies and Drug Release Kinetics

The aim of the present work was to investigate the role of montmorillonite clay as an oral drug delivery carrier for in vitro controlled release of anti-inflammatory drug diclofenac sodium (DS). For this purpose, the adsorption behaviour of DS onto the clay was studied as a function of pH of the aqueous drug solution, contact time, initial drug concentration and clay dosage. The clay-drug composites synthesized were subsequently characterized by X-ray diffraction studies, Fourier transform-infrared studies, differential scanning calorimetric analysis, thermogravimetric analysis, zeta-potential measurement, scanning electron microscopic and high-resolution transmission electron microscopic techniques. A drug loading of 497 mg/g was obtained in case of intercalated clay-drug composite. The in vitro drug release studies of the synthesized clay-drug composites in simulated gastric fluid (pH 1.2) showed no release, whereas a prolonged drug release profile was obtained for the intercalated clay-drug composite i...

Application of Artificial Neural Networks in Prediction of Diclofenac Sodium Release From Drug-Modified Zeolites Physical Mixtures and Antiedematous Activity Assessment

In this study, utilization of artificial neural network (ANN) models [static-multilayer perceptron (MLP) and generalized regression neural networks and dynamic-gamma one-layer network and recurrent one-layer network] for prediction of diclofenac sodium (DS) release from drug-cationic surfactant-modified zeolites physical mixtures comprising different surfactant/drug molar ratio (0.2-2.5) was performed. The inputs for ANNs trainings were surfactant/drug molar ratios, that is, drug loadings in the drug-modified zeolite mixtures, whereas the outputs were percents of drug release in predetermined time points during drug release test (8 h). The obtained results revealed that MLP showed the highest correlation between experimental and predicted drug release. The safety of both natural and cationic surfactant-modified zeolite as a potential excipient was confirmed in an acute toxicity testing during 72 h. DS (1.5, 5, 10, mg/kg, p.o.) as well as DS-modified zeolites mixtures produced a significant dose-dependent reduction of the rat paw edema induced by proinflammatory agent carrageenan. DS antiedematous effect was intensified and prolonged significantly by modified zeolite. These results could suggest the potential improvement in the treatment of inflammation by DS-modified zeolite mixtures.