Release Profiles Of Diclofenac Sodium Research Articles

DIFUCOSIN: DIclofenac sodium salt loaded FUCOidan-SericIN nanoparticles for the management of chronic inflammatory diseases

The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1β with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.

Development of Modified-Release Diclofenac Sodium Capsules Using Blends of Pectin-Clay Multiparticulate Hybrid Systems as Release Retardants

A combination of inorganic and organic hybrid systems is of high research interest as they provide novel hybrid systems for the improvement of existing properties, overcoming limitations of the parent materials, and for the optimization of their controlled release potential. This study sorted to develop and pharmaceutically assess the release profile of diclofenac sodium using cocoa pod husk (CPH) blended with different proportions of either talc or bentonite as multiparticulate composite release modifiers. Preformulation investigations of the multiparticulate hybrid systems included pH, swelling index, moisture content, elemental contents, and flow properties. The FTIR was also used to investigate the compatibilities between pectin and bentonite (PB), pectin and talc (PT), and diclofenac and pectin-talc (DPT), as well as diclofenac and pectin-bentonite (DPB). The diclofenac content, uniformity of the weight of capsules, in vitro drug release, and the kinetics and mechanism of release of diclofenac from the hybrid systems were also investigated using mathematical models. The pectin yield was 23.3%, with the water-holding capacities of pectin-talc (PT) and pectin-bentonite (PB) hybrid systems being 6.4% and 5.0%, respectively. The swelling indices of PT and PB were 110.0 and 130.0 in 0.1 M HCL at pH 1.2 and 130.0 and 149.0 in phosphate buffer at pH 6.8, respectively. This system was also found to exhibit excellent flow properties, and there were no diclofenac-excipient interactions. All formulated batches passed the pharmacopoeial and nonpharmacopoeial tests. They also demonstrated controlled release properties via different release kinetics and mechanisms. This study shows that the pectin-talc and pectin-bentonite multiparticulate composites could be used as release modifiers in pharmaceutical preparations.

Ispitivanje bioekvivalencije Diklofenaka - efekti Eudragita, pripreme tableta i karakteristika formulacija na profile oslobađanja i mjere bioraspoloživosti

Objective. The study was aimed to evaluate the effects of changing excipients, including type of Eudragit polymer, on release and absorption profiles in vitro and in vivo, of tablets containing the antiinflammatory drug, diclofenac sodium. Methods. Formulation 1 consisted of diclofenac sodium tablets containing Eudragit L30, and Formulation 2 consisted of diclofenac sodium tablets containing Eudragit L100, and both formulations contained different excipients. Tablets were assessed, in vitro, for weight, hardness, diameter, thickness, mass uniformity, disintegration and dissolution profiles and drug content. Tablets were also assessed in vivo by gavage in healthy rabbits and assessing diclofenac sodium plasma concentrations and pharmacokinetic parameters. Results. Results showed that in vitro analyses demonstrated non-equivalence while in vivo analyses demonstrated equivalence. This suggests that although different types of Eudragit and excipients modulated the in vitro dissolution and release profiles of diclofenac sodium, in vivo absorption in rabbits remained similar representing bioequivalence. Conclusion. It is needed to conduct evaluations of bioequivalence of diclofenac sodium oral preparations at both in vitro and in vivo conditions.

Nanocarriers as Promising Novel Systems for Controlled Delivery of Diclofenac Sodium

The formulation and evaluation of diclofenac sodium from liposomes, niosomes and nanoemulsion are analyzed. The release profiles of diclofenac sodium were almost similar in all the formulations. It is found that 85% of diclofenac sodium diffused out from the colloidal systems within 8hrs and practically all the drug was released within 12hrs. In addition to this controlled release, the similarity of the release profiles obtained for liposomes, niosomes and nanoemulsion signifies that the internal structure has little role in the release process. The drug released fast and completely from the carriers upon high dilution, but it is slowed down a little when they are not diluted. The maximium amount of diclofenac sodium was released from nano emulsion as well as liposomes after 12 hrs at 1 in 200 dilution where as in niosomes, it was found at 1 in 100 dilution. But surprisingly, the release was decreased upon further dilution. The higher the surfactant content, the higher the globule size of the nanoemulsion. The mean size of the systems was decreased upon increasing dilution. Among all the systems, the mean size of niosomes was decreased upon increasing the dilution up to 1:200. It was finally depicted that the dilution effect on the zeta potential of the systems shifted from negative to positive by adding polysorbate 80. The zeta potential of all the systems was significantly good indicating stable systems.

The effect of different grades polymer blends on release profiles of diclofenac sodium from hydrophilic matrices

Formulation of Diclofenac Sodium tablets using Tapioca starch powder- A promising binderYamini.K, Chalapathi. V, N. Lakshmi Narasimha Reddy, K.V. Lokesh, S. Praveen Kumar Reddy, Gopal.V.

Preparation and evaluation of bioactive and compatible starch based superabsorbent for oral drug delivery systems

Novel types of highly swelling hydrogels (superabsorbent) were prepared by grafting crosslinked poly acrylic acid-co-2-hydroxyethylmetacrylate (PAA-co-HEMA) chains onto starch through a free radical polymerization method. The effect of grafting variables (i.e., concentration of methylenebisacrylamide (MBA), acrylic acid/2-hydroxy methymetacrylate (AA/HEMA) weight ratio, ammonium persulfate (APS), starch, neutralization percent, were systematically optimized to achieve a hydrogel with a maximum swelling capacity. The superabsorbent (SAP) formation was confirmed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The controlled-release behavior of diclofenac sodium (DS) from SAP was investigated and showed that the release profiles of DS from superabsorbent polymer were slow (less than 6 %) in simulated gastric fluid (SGF, pH1.6) over 3h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH7.4) within 8h after changing media. Overall, the results demonstrated that biodegradable superabsorbent could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates for an orally administrated drug delivery system.

The effect of hydrophilic and hydrophobic polymers on release profiles of diclofenac sodium from matrix tablets

Objective: The current study aimed to develop a matrix type sustained release Diclofenac tablet, using hydrophilic hydroxypropyl methylcellulose (HPMC) and hydrophobic polymer cetyl alcohol (CA). Materials and Methods: Two different polymers, that is, Methocel K15MCR ® and CA were used in various proportions as release controlling factor. Matrix tablets were prepared by wet granulation technique. The physicochemical properties of the granules and tablets were evaluated. In vitro dissolution studies of prepared matrix tablet and patent product Voltaren SR ® tablet (VSR) were performed at pH 7.4 phosphate buffer at 100 rpm, and at 37 ± 0.5°C, and subjected to in vitro bioequivalence study in terms of similarity and difference factors. Stability studies were conducted for 6 months using optimized formulation for extended period of time, both at room temperature and accelerated conditions. The dissolution data were fit to Zero‑order, First‑order, Higuchi, and Korsmeyer‑Peppas’ equations. Results: The formulated tablets showed acceptable weight variation, hardness, drug content uniformity with sustained release matrix characteristics. Hydrophilic Methocel K15 MCR ® matrices‑based tablets showed zero‑order and hydrophobic CA matrices‑based tablets followed first‑order kinetics except for formulation six (F6 showed zero‑order profile). It was found that formulations containing CA showed better dissolution properties with respect to formulations containing Methocel K15 MCR ® in terms of similarity and difference factor. Furthermore, the formulations F4, F5, and F6 exhibited similar drug release profile as compared with VSR tablet, which indicated that these formulations could be bioequivalent with VSR tablet in vitro. Tablets were stable both at room temperature and as well as at accelerated conditions. Conclusion: The present study demonstrated that Diclofenac could be successfully prepared using an appropriate amount of Methocel K15 MCR ® and CA in the form of matrix tablets with similar dissolution profile of patent product Voltaren SR ® . The type of polymers used was found to induce a profound effect on release rate and mechanism.

Electrospun poly(L-lactide) membranes containing a single drug or multiple drug system for antimicrobial wound dressings

Micro- and nanofibrous electrospun poly(L-lactide) (PLA) and PLA/poly(ethylene glycol) (PEG) membranes containing diclofenac sodium (DS), lidocaine hydrochloride (LHC), benzalkonium chloride (BC), or combinations thereof (DS/LHC and DS/LHC/BC) have been developed. The addition of low molecular weight organic salts to the spinning PLA and PLA/PEG solutions results in increased conductivity and contributes to the preparation of membranes composed of fibers that are well-aligned with the collector rotation direction. The water contact angle values of the PLA and PLA/PEG membranes are characteristic of hydrophobic surfaces. The incorporation of LHC in the fibers does not lead to membrane hydrophilization. In contrast to LHC, other drugs or combinations thereof have led to the preparation of hydrophilic fibrous materials. The hydrophilization is due to the presence of DS or BC fragments or functional groups on the fibrous membrane surfaces as verified by X-ray photoelectron spectroscopy (XPS). As evidenced by the differential scanning calorimetric study and X-ray diffraction analysis data, the drugs incorporated in the fibers are in the amorphous state. The release profiles of DS, LHC, and BC from the PLA/drug and PLA/PEG/drug fibrous membranes depend on the drug nature and, in the case of BC, on the composition of the polymer scaffold as well. The release of DS and LHC from the PLA/DS/LHC and PLA/PEG/DS/LHC membranes is slower compared to that of the single drug-loaded membranes. This phenomenon has been attributed to an ionic interaction between the two drugs. Microbiological studies have demonstrated that the PLA/DS, PLA/BC, PLA/DS/LHC, and PLA/DS/LHC/BC membranes exhibit antibacterial activity against Staphylococcus aureus. Open image in new window

Biopharmaceutical assessment of a polycomplex matrix system based on carbomer 940 and Eudragit® EPO for colon-specific drug delivery

The biopharmaceutical properties of a new drug carrier based on an interpolyelectrolyte complex (IPEC) between Carbomer 940 and Eudragit® EPO have been studied in the form of a polycomplex matrix system (PMS) intended to be a potential carrier for peroral drug delivery systems. The release profiles of diclofenac sodium from the proposed PMS and Voltaren® retard in model gastroitestial tract medium belong to the intestine-soluble and sustained-release types, respectively. Evaluation of the pharmacokinetic parameters of the PMS revealed a close in vitro/in vivo correlation. The proposed PMS, in contrast to the parent drug, provides targeted drug delivery to the colon region and is comparable with Voltaren® retard with respect to the bioavailability and the main pharmacokinetic parameters.

Pharmaceutical Microencapsulation Technology for Development of Controlled Release Drug Delivery systems

This article demonstrated development of controlled release system of an NSAID drug, Diclofenac sodium employing different ratios of Ethyl cellulose. Diclofenac sodium and ethyl cellulose in different proportions were processed by microencapsulation based on phase separation technique to formulate microcapsules. The prepared microcapsules were then compressed into tablets to obtain controlled release oral formulations. In-vitro evaluation was performed by dissolution test of each preparation was conducted in 900 ml of phosphate buffer solution of pH 7.2 maintained at 37 ± 0.5 °C and stirred at 50 rpm. At pre- determined time intervals (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 hrs). The drug concentration in the collected samples was determined by UV spectrophotometer at 276 nm. The physical characteristics of diclofenac sodium microcapsules were according to accepted range. These were off-white, free flowing and spherical in shape. The release profile of diclofenac sodium from microcapsules was found to be directly proportional to the proportion of ethylcellulose and coat thickness. The in-vitro release pattern showed that with ratio of 1:1 and 1:2 (drug: polymer), the percentage release of drug at first hour was 16.91 and 11.52 %, respectively as compared to 1:3 which is only 6.87 % with in this time. The release mechanism followed higuchi model for its release pattern. Tablet Formulation (F2) of present study was found comparable in release profile the marketed brand Phlogin-SR, microcapsules showed an extended release beyond 24 h. Further, a good correlation was found between drug release and proportion of ethylcellulose in the microcapsules. Microencapsulation based on coacervation found as good technique to control release of diclofenac sodium for making the controlled release formulations. Keywords—Diclofenac sodium, Microencapsulation technology, Ethylcellulose, In-Vitro Release Profile

Alginate‐based biodegradable superabsorbents as candidates for diclofenac sodium delivery systems

AbstractNovel types of highly swelling hydrogels were prepared by grafting crosslinked polyacrylamide‐co‐poly‐2‐acrylamido‐2‐methylpropane sulfonic acid (PAAm‐co‐PAMPS) chains onto sodium alginate (Na‐Alg) through a free radical polymerization method. The superabsorbent formation was confirmed by Fourier transform infrared spectroscopic (FTIR). The controlled release behavior of diclofenac sodium (DS) from superabsorbent polymer was factinvestigated, and shown that the release profiles of DS from superabsorbent polymer were slow in simulated gastric fluid (SGF, pH 1.2) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 7.4) within 21 h after changing media. Overall the results demonstrated that biodegradable superabsorbent could successfully deliver a drug to the intestine without losing the drug in the stomach, and could be potential candidates as an orally administrated drug delivery system. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Probiotic-assisted colon-specific delivery of diclofenac sodium from guar gum matrix tablets: In vitro evaluation

Purpose: The aim of present work was to investigate the in vitro release profile of diclofenac sodium from matrix tablets,which were prepared using guar gum with and without probiotics. Methods: Six matrix tablets formulations (F1-F6) of diclofenac sodium containing varying proportions of guar gum, 10-60% of tablet weight were prepared by wet granulation method and evaluated in vitro for their release profile. Four matrix tablets formulations (F7-F10) of diclofenac with guar gum (40%) were prepared incorporating varying concentration of commercial spores of lactobacillus and bifidobacterium species that are commonly found in colon microflora. Results: The tablets having same concentration of guar gum without probiotics (F4) showed a 54.47% cumulative release of diclofenac after 24 hr while that in presence of probiotics (F9) was 73.01%. These drug release studies were conducted without rat caecal content. In another set of experiments, the drug release studies were carried out in presence of rat caecal content. In such experiments, more than 95% drug was released from F4 and F9 formulations after 24 hr. Conclusion:The results showed that commercial probiotics are capable in digesting guar gum. These probiotics may be used to assist in colon delivery of drugs from formulations prepared with guar gum.

Application of Design of Experiments and Multilayer Perceptrons Neural Network in the Optimization of Diclofenac Sodium Extended Release Tablets with Carbopol 71G

The purpose of the study was to screen the effects of formulation factors on the in vitro release profile of diclofenac sodium from matrix tablets using design of experiment (DOE). Formulations of diclofenac sodium tablets, with Carbopol 71G as matrix substance, were optimized by artificial neural network. According to Central Composite Design, 10 formulations of diclofenac sodium matrix tablets were prepared. As network inputs, concentration of Carbopol 71G and the Kollidon K-25 were selected. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. The independent variables and the release parameters were processed by multilayer perceptrons neural network (MLP). Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 h to more than 8 h to complete dissolution. For two tested formulations there was no difference between experimental and MLP predicted in vitro profiles. The MLP model was optimized. The root mean square value for the trained network was 0.07%, which indicated that the optimal MLP model was reached. The optimal tablet formulation predicted by MLP was with 23% of Carbopol 71G and 0.8% of Kollidon K-25. Calculated difference factor (f(1) 7.37) and similarity factor (f(2) 70.79) indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. The satisfactory prediction of drug release for optimal formulation by the MLP in this study has shown the applicability of this optimization method in modeling extended release tablet formulation.

Mucoadhesive sustained delivery of diclofenac sodium using carbopol 675 and PVP admixtures as mucoadhesive motif

The mucoadhesiveness, swelling characteristics and release profile of diclofenac sodium from mucoadhesive tablets prepared with Carbopol 675 and polyvinyl pyrrolidone (PVP) and their physical mixtures were studied to evaluate their applicability in sustained drug delivery. The ex-vivo mucoadhesive strengths of the tablet compacts were determined by tensiometry using Lecomte du Nuoy tensiometer and everted pig jejunum. Release studies were carried out in three different pH media (1.2, 7.0 and 7.5). The results of mucoadhesive test revealed that tablets formulated from 1:1 physical mixture of Carbopol 675 and PVP had the highest mucoadhesive strength, which showed they bound tightly to the mucus pig jejunum. Their low swelling and release behaviours also indicated that the tablet compacts are very good candidates for sustained release formulation since release of diclofenac sodium was sustained by the compacts.

Evaluation of Diclofenac Sodium Release from Matrix Pellets Compressed into MUPS Tablets

The purpose of the study was to screen the effects of formulation factors on the in vitro release profile of diclofenac sodium from matrix pellets compressed into multiple unit pellet system (MUPS) tablets using design of experiment (DOE). Extended release of diclofenac sodium was accomplished using Carbopol 71G as matrix substance. According to Fractional Factorial Design FFD 2(3-1) four formulations of diclofenac sodium MUPS matrix tablets were prepared. The process of direct pelletization and subsequently compression of the pellets into tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve a better control of the process factors over the principal response - the release of the drug. The investigated factors were X1-the percentage of polymer Carbopol 71G, X2-crushing strength of the tablet and X3-different batches of the diclofenac sodium. In vitro dissolution time profiles at 6 different sampling times were chosen as responses. Results of drug release studies indicated that drug release rates vary between different formulations, with a range of 1 to 8 h to complete dissolution. The most important impact on the drug release had factor X1-the percentage of polymer Carbopol 71G. The polymer percentage is suggested as release regulator for diclofenac sodium release from MUPS matrix tablets. All other investigated factors had no significant influence on the release profile of diclofenac sodium.

Preparation and in vitro evaluation of sustained release tablet formulations of diclofenac sodium

The effects of formulation variables on the release profile of diclofenac sodium (DS) from hydroxypropylmethyl cellulose (HPMC) and chitosan matrix tablets were studied. DS tablets were prepared by wet granulation and direct compression methods and different ratios of HPMC and chitosan were used. Physical properties of the prepared tablets and targeted commercial sustained release (SR) tablet and the drug release were studied in tablets that were placed in 0.1 M HCl for 1 h and phosphate buffer solution was added to reach pH value of 7.5. In vitro studies showed that 20% HPMC contained SR formulation with direct (dry) compression method is the optimum formulation due to its better targeting profile in terms of release. This formulation also exhibited the best-fitted formulation into the zero order kinetics. The precision and accuracy of the analytical method were also checked. The repeatability and reproducibility of the method were also determined.

Oral sustained delivery of diclofenac sodium using calcium chondroitin sulfate matrix

Chondroitin sulfate (CS) is a potential candidate for colon-specific drug carriers. However, the readily water-soluble nature limits its application as a solid-state drug-delivery vehicle. In this study, the CS formation of a polyelectrolyte complex (PEC) with Ca2+ (CS-Ca) was adapted to retain CS in a solid form for use in a drug-delivery system. Pre-treated CS with poly(ethylene glycol) diglycidyl ether (EX-810) followed by complexation with Ca2+ was also tested (CS-Ca-EX). Diclofenac sodium was used as a drug probe to evaluate the performance of the drug-release behavior of the complexes. The amount of diclofenac sodium released was higher in simulated intestinal fluid (SIF) than in simulated gastric fluid (SGF) due to the anionic groups on CS or the higher solubility of drug itself in PBS. The release profile of diclofenac sodium from CS-Ca-EX was most notably sustained when compared to other groups. Enzymatic degradation by chondroitinase ABC of CS, CS-Ca and CS-Ca-EX exhibited a similar degradation mechanism and GPC revealed the dissolution rate of CS from the three matrix types was, in decreasing order: CS, CS-Ca, CS-Ca-EX. The synergy of the anti-inflammatory activity of diclofenac sodium in CS-based complexes was evaluated using the carrageenan-induced edema rat test. The percentage of swelling was lower for all experimental groups as compared to the control, untreated group. The anti-inflammatory activity of diclofenac in the CS matrix gradually increased up to 9 h but CS-Ca or CS-Ca-EX matrices showed less potency than the CS matrix in reducing inflammation.

Complexation Between PVP and Gantrez Polymer and Its Effect on Release and Bioadhesive Properties of the Composite PVP/Gantrez Films

Complexation between poly(methyl vinyl ether‐maleic anhydride) copolymer (Gantrez AN 169) and polyvinylpyrrolidone (PVP K‐90D) in aqueous solutions were investigated using a viscometric method and Raman spectroscopy. The composite films with different weight ratios of PVP to Gantrez were prepared in the presence of N‐methyl‐2‐pyrrolidone. The release profiles of diclofenac sodium (DS) from these films were determined and the bioadhesive properties measured. An interpolymer complex was formed through hydrogen bonding between the carbonyl groups of PVP and the hydroxyl groups of Gantrez. The formation of interpolymer hydrogen bonds reduced the interaction of the polymers with water molecules, thus resulting in a lower solubility of the complex in water and a further retarded release of DS from the composite films. The interpolymer complexation was also found to increase the bioadhesive properties of the composite films to a silicone elastomer substrate. The complexation of PVP and the Gantrez copolymer in the composite films was a critical factor affecting the release of DS from the films and the bioadhesive properties of the films.

The effect of polymer blends on release profiles of diclofenac sodium from matrices

The purpose of this study was to evaluate the effect of polymer blends on the in vitro release profile of diclofenac sodium. Several controlled release matrices of diclofenac sodium with different proportions of hydroxypropyl methylcellulose (HPMC; viscosity grade 60 and 500 mPa.s), carbopol 940 and lactose as a water soluble filler were prepared. The results showed that when HPMC (viscosity grade 60 mPa.s) alone was used as matrix former, diclofenac sodium was released fast but the release rate became slower with HPMC (viscosity grade 500 mPa.s) at higher polymer/drug ratios (more than 0.8:1). However in lower polymer/drug ratios (lower than 0.7:1) the release rate still was fast. The results showed that carbopol can extend the release time appreciably but the release profiles had considerable fluctuations, and drug release in first hours was slow but increased appreciably with time at the end of profiles. When an appropriate blend of HPMC (viscosity grade 60 or 500 mPa.s) and carbopol 940 was used, the drug release became more uniform and its kinetic approached to zero order and release fluctuations were diminished. The results with these polymer blends showed that it is possible to reduce the total amounts of polymer in each formulation. According to kinetic analysis data, drug release from these matrix tablets did not follow Fick's law of diffusion and the results were in agreement with the earlier reports.

INFLUENCE OF FORMULATION PARAMETERS ON THE RELEASE OF DICLOFENAC SODIUM FROM MARICES WITH MANUFACTURING FORMULATION IN GREDIENTS

Effects of formulation parameters on the fractional release profile of diclofenac sodium from matrices having the manufacturing formulation ingredients are studied. As a content of cetyl alcohol (rate controlling agent) in the matrix increases, the fractional release decreases. The fractional release increases either by increasing sucrose content outside the granule or by decreasing sucrose content inside the granule. Results presented here indicate that as PVP content outside the granule or aerosol fraction inside or outside the granule in the matrix increases, the fractional release increases. The fractional release profiles of diclofenac sodium from matrices, when each ingredient is inside or outside, or half inside - half outside the granule, are compared.