Sustained Release Of Indomethacin Research Articles

Formulation and Evaluation of Indomethacin Sustained Release Tablet by using Natural Polymers

Arthritis is most prevalent disorder and Indomethacin is choice of drug for arthritis. Oral route is most preferred route of drug administration and tablets are the more convenient dosage form. In present research natural polymers guar gum and xanthan gum were used to make sustained release tablet of Indomethacin. Indomethacin release from the tablets was studied in phosphate buffer pH 7.2. The drug release pattern of six different formulations in which xanthan gum and guar gum were used as a retarding material in different proportions was shown in table no. 6. The formulation F1 releases (75.20%) upto 12 hrs whereas the formulation F2 releases the drug (98.81%) in same time. The formulations F3, F4, F5 and F6 release 98.32%, 99.29%, 98.79% and 82.40% respectively. The dissolution pattern of both gums was similar i.e. with drug to polymer ratio (1:1). In present work F1 shows best sustained release upto 12 hrs in which Drug to Polymer ratio was 1:1:0 (Drug : Xanthan gum : Guar gum). In formulation F2 drug release was not sustained and complete release occurs in 12 hrs where the Drug to Polymer ratio was 1:1.67:0 (Drug: Xanthan gum : Guar gum). It was found that on the concentration of xanthan gum decreases the release rate of the drug also decreases. For sustain release there is not much role of Guar Gum reported. Indomethacin drug has been selected which has half-life 4.5 hrs. Hence the present work, an attempt has been made to provide sustained release drug delivery using polymers with Indomethacin as the model drug. Xanthan gum was best able to retard Indomethacin release mechanism even in the presence of a polymer. Polymer can be used to formulate successful sustained release Indomethacin matrix tablets that have desirable characteristics.

Effect of Solvents, Stabilizers and the Concentration of Stabilizers on the Physical Properties of Poly(d,l-lactide-co-glycolide) Nanoparticles: Encapsulation, In Vitro Release of Indomethacin and Cytotoxicity against HepG2-Cell

A biocompatible, biodegradable and FDA-approved polymer [Poly lactic-co-glycolic acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of solvents, stabilizers and their concentrations on the physical properties of the PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects of different proportions of PVA/PVP with DCM/chloroform on the physiochemical properties (particle size, the polydispersity index, the zeta potential by Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was used to check the physical state, the possible complexation of PLGA with stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. Average size of 273.2–563.9 nm was obtained when PVA (stabilizer) with DCM, whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 273.2–563.9 nm when PVP was the stabilizer with DCM, while it was 381.4–466.6 nm with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative (−0.62 mV) while they were comparatively higher and positive for PVP-stabilized NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1–3%), which resulted in sufficient encapsulation (54.94–74.86%) and drug loading (4.99–6.81%). No endothermic peak of PVA/PVP appeared in the optimized formulation, which indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro release study indicated a sustained release of IND (32.83–52.16%) from the PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics followed by Korsmeyer–Peppas models. The cell proliferation assay clearly established that the organic solvents used to prepare PLGA-NPs had evaporated. The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the dose range of IND (250–500 µg/mL) and at an equivalent concentration of PLGA-NPs (3571.4–7142.7 µg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced by its encapsulation into PLGA-NPs. The outcomes of this investigation could be implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of low/high molecular weight drugs. It would be useful for further in vitro and in vivo applications to use this delivery system.

FORMULATION DEVELOPMENT AND EVALUATION OF ALMOND GUM BASED SUSTAINED RELEASE MATRIX TABLET OF INDOMETHACIN

Objective: The aspiration of the current research involves employing various concentrations of polymer and filler to develop indomethacin sustained release (SR) matrix tablets. The objective of this research work is to reduce dosing frequency thereby increasing patients compliance and enhanced therapeutic activity.Methods: Polymers such as Almond gum (AG), polyvinylpyrrolidone (PVP), and starch at different concentrations were used for formulating SR polymeric matrix tablets. Evaluation of pre-compression and post-compression parameters was done for both granules and formulated tablets.Results: Results obtained from pre-compression parameters and post-compression parameters suggested that all the parameters are within the prescribed limits, demonstrating that formulated granules had shown better flow properties. The morphological characteristics of the developed tablet were observed by employing scanning electron microscope where the surface of the tablet was found to be smooth from the in vitro dissolution study, combination of AG (30 mg) with PVP (30 mg), and starch used as a filler has sustained the release of drug up to 10 h.Conclusion: Therefore, developed polymeric matrix tablet exhibited enhanced potency over a conventional tablet by exhibiting an excellent dissolution profile for a period of 10 h.

Alginate encapsulated mesoporous silica nanospheres as a sustained drug delivery system for the poorly water-soluble drug indomethacin

We applied a combination of inorganic mesoporous silica material, frequently used as drug carriers, and a natural organic polymer alginate (ALG), to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin (IND). Mesoporous silica nanospheres (MSNs) were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis. After drug loading into the pores of aninopropyl functionalized MSNs (AP-MSNs), IND loaded AP-MSNs (IND-AP-MSNs) were encapsulated by ALG through the ionic interaction. The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, zeta-potential analysis and TGA analysis. The surface structure and surface charge changes of the ALG encapsulated AP-MSNs (ALG-AP-MSNs) were also investigated. The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG. We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.

Solidified Reverse Micellar Solution (SRMS)-Based Indomethacin Sustained-Release Tablets: Formulation and <i>In vitro</i> Evaluation

Purpose: To formulate and evaluate sustained-release indomethacin tablets based on solidified reverse micellar solution (SRMS).Methods: SRMS consisting of mixtures of phospholipid (Phospholipon® 90H) and triglyceride (Softisan® 154) were prepared in the ratios of 1:1, 2:1 and 1:2, respectively. SRMS-based tablets containing 75 mg of indomethacin each were prepared using a validated plastic mould. The physicochemical properties of the tablet formulations were studied. In vitro release study was carried out in simulated intestinal fluid (SIF, pH 7.5).Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix used (p < 0.05). Tablet hardness ranged from 5.00 ± 0.39 to 5.60 ± 0.36 kgf for tablets formulated with SRMS 1:2 and 2:1 (N3 and N2), respectively. The tablets exhibited friability of < 1 % (p < 0.05). Erosion time in SIF ranged from 124.0 ± 0.5 to 180.0 ± 1.1 min while drug release from the tablets reached a maximum in 8 – 11 h for all thebatches.Conclusion: Indomethacin tablets based on SRMS exhibited good sustained-release properties and can be further developed to achieve once daily administration for improved patient adherence to therapy.Keywords: Solidified reverse micellar solution, Phospholipid, Triglyceride, Indomethacin, Sustained release.

Fabrication of Hydrogel Beads Entrappted by Mesoporous Silicates Nanoparticles for pH-sensitive and Sustained Release of Indomethacin

Fabrication of Hydrogel Beads Entrappted by Mesoporous Silicates Nanoparticles for pH-sensitive and Sustained Release of Indomethacin

Enzymatically in situ shell cross-linked micelles composed of 4-arm PPO–PEO and heparin for controlled dual drug delivery

We report a controlled dual drug delivery system using heparinized 4-arm poly(propylene oxide) (PPO)–poly(ethylene oxide) (PEO) micelles (cHTM) that are sterically stabilized by enzymatic shell cross-linking (SCL). Tyramine (TA) was chemically conjugated to 4-arm PPO–PEO (Tetronic) and heparin, resulting in Tetronic–TA (Tet–TA) and heparin–TA (Hep–TA), respectively. To prepare a series of cHTM, different amounts of Hep–TA were added to a micellar solution of Tet–TA, followed by addition of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) to trigger SCL between TA groups at the micellar surfaces. Increasing the feed amount of Hep–TA led to increased heparin content of cHTM, thereby resulting in increased micelle size with more negatively charged surfaces. All SCL micelles were found to be highly stable over 4weeks, showing negligible changes in their sizes and zeta potentials. Dual drug-loaded cHTM containing indomethacin (IMC) and basic fibroblast growth factor (bFGF) were prepared via a one-pot procedure. With favorable IMC loading, the loading efficiencies of bFGF into cHTM were much higher than those in the controls due to the presence of heparin on the micellar surface. After bFGF was added to IMC loaded cHTM the surface of HTM became less negative with an increase in size, suggesting successful binding of positively charged bFGF to heparinized micelle surfaces. In vitro release data clearly showed more sustained release of IMC and bFGF as compared with non-cross-linked micelles. Based on these results, we suggest that cHTM can be used as a new drug delivery platform for controlled dual drug release.

MAPLE deposition of PLGA:PEG films for controlled drug delivery: Influence of PEG molecular weight

Implantable devices consisting of indomethacin (INC) cores coated with poly(lactide-co-glycolide):polyethylene glycol films (i.e. PLGA:PEG films) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) were produced. To predict their behavior after implantation inside the body, the implants were studied in vitro, in media similar with those encountered inside the body (phosphate buffered saline (PBS) pH 7.4 and blood). The influence of the molecular weight of PEG (i.e. low (1450Da) versus high (10kDa) molecular weights) on the characteristics of the implants was investigated, in terms of morphology, blood compatibility and kinetics of the drug release. The use of PEG of high molecular weight resulted in larger pores on the implants surfaces, enhanced blood compatibility of the implants and higher drug delivery rates. For both molecular weights PEGs, sustained release of INC was maintained over a three weeks interval. Theoretical fitting of the drug release data with Higuchi's model indicated that the INC was released mainly by diffusion, most probably through the pores formed in PLGA:PEG films during PBS immersion.

Sustained release of indomethacin from chitosan granules in beagle dogs.

The potential of chitosan granules as an oral sustained-release dosage form of indomethacin has been compared with conventional capsules in beagle dogs. When a commercial capsule was administered orally, the plasma concentrations reached the maximum level in 30 min. The granules did not give a sharp peak to the plasma concentration, but produced a sustained plateau of the drug. This may be due to the slow rate of release and a longer residence time in the stomach. Thus, in terms of reducing the peak in plasma concentration and maintenance of drug concentration in plasma, the chitosan granules were superior to conventional capsules.

Indomethacin sustained release pellets prepared by extrusion-spheronization

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10 % w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20 %) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10 % has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.

LOCALLY MADE CHITOSAN COVALENTLY LINKED TO INDOMETHACIN: A NOVEL APPROACH TO FORMULATE SUSTAINED RELEASE INDOMETHACIN CAPSULE IN BASRAH

The sustained release capsules are pharmaceutical dosage form used for the treatment of chronic rather than acute diseases and are useful because of its convenience and less side effects. This work describes an attempt to formulate indomethacin sustained release capsule using indomethacin covalently linked to chitosan. Chitosan was prepared by alkaline -N-deacetylation of chitin, which was isolated from the shells of local shrimps. The yield of chitosan was found to be 80%. This polymer was found to be white crystal, odorless and the IR spectroscopy of it was similar to a standard reference. Chitosan has been covalently linked to indomethacin and the ratio of drug to polymer was found to be 5:1. The chemical interaction between the drug and the polymer was proved by IR studies. In vitro release at different pH were performed and the release of indomethacin in the prepared sustained release capsule were tested and compared with conventional indomethacin capsule INDOMIN-25mg, and a commercial sustained release capsule INDO-75-SR. The release of indomethacin in our product was completed within 12 hours, while the conventional INDOMIN capsule and commercial INDO-75-SR capsule released within 2.5 and 5 hours respectively. In conclusion a cheap, locally made chitosan can be used in formulation of sustained release capsules by covalently linked to drugs containing carboxyl group (like indomethacin) or can be modified to have a carboxyl group.

Rosin microparticles as drug carriers: Influence of various solvents on the formation of particles and sustained-release of indomethacin

The aim of this study was to formulate a sustained release system for indomethacin (IND) with rosin gum obtained from a pine tree. Rosin microparticles were prepared by a dispersion and dialysis method without the addition of surfactant. In order to investigate the influence of solvents on the formation of colloidal microparitcles, various solvents like ethanol, DMF, DMAc, and acetone were used. The rosin microparticles containing IND were characterized by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The morphologies of rosin microparticles observed by scanning electron microscopy (SEM) were spherical. The solvents used to dissolve rosin significantly affected the drug content and drug release rate of IND. The release behaviors of IND from the rosin microparticles were dependent on the drug content and size of the particles. Rosin microparticles with a higher drug content and of a larger particle size had a slower drug release rate. Also, the IND release rate from the rosin microparticles could be regulated by the rosin content in the microparticles. From these results, rosin microparticles have the potential of being used as a sustained release system of IND.

In vitro drug liberation and kinetics of sustained release indomethacin suppository

The aim of this study was to formulate sustained release (SR) suppositories containing indomethacin (IND) microspheres. In the first part of the study, IND microspheres were prepared by solvent evaporation method. Ethyl cellulose was used as polymer. Shape and surface charactheristics, particle size and size distribution of microspheres were determined. The effect of drug: polymer ratio and stirring rate on microsphere formation, average particle size, drug loading capacity and in vitro IND release were investigated. The highest drug loading capacity was found with 1:1 drug–polymer ratio. Stirring rate caused insignificant effect on drug loading capacity but particle size. Increase in stirring rate resulted in a decrease in particle size. In the second part, SR suppositories were formulated by incorporating IND microspheres having the highest drug loaded. The bases used were PEG mixtures (400:1500:4000) and Witepsol H15. Qualitative controls and IND assay on the suppositories were carried out. The drugs released were evaluated by in vitro dissolution tests. Comparative results of SR suppositories containing IND microspheres with that of conventional ones showed that the former has sustained effect up to 480 min in vitro. Release results were evaluated kinetically and the data was fitted (Bt) a kinetics.

Indomethacin sustained release from alginate-gelatin or pectin-gelatin coacervates

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IMC) sustained release microparticles (pellets) were prepared from pectin-gelatin or alginategelatin hydrocolloid coacervate systems under controlled pH and temperature conditions. Delayed release up to 14 h was obtained with pectin-gelatin or alginate-gelatin systems of varying composition. With the pectin-gelatin systems a low drug to hydrocolloid ratio and low pectin to gelatin ratio was the most optimal composition for sustained release. Incorporation of additives such as carnauba wax was essential for diffusion controlled mechanisms to operate in the alginate-gelatin systems. Additives also showed improvements in particle shape, size distribution and flow properties. The results of this study offer an inexpensive alternative form of sustained release IMC.

Bioavailability of sustained release indomethacin suppositories containing polycarbophil

The bioavailability of indomethacin from polyethylene glycol base, commercial suppositories Indocid ∗, MSD and from polyethylene glycol base containing 5, 6 and 8% of polycarbophil, with the purpose of obtaining a controlled release suppositories, was determined in dogs. The results show that polycarbophil as a bioadhesive increased absorption and improved the bioavailability of indomethacin where the areas under the curves for the commercial suppositories and those containing 0, 5, 6 and 8% polycarbophil were 19.5, 14.9, 31.2, 21.4 and 21.2 μ h ml −1, respectively. The maximum plasma concentration ( C max) and the time to reach C max ( t max) were 4.76, 2.98, 4.50, 2.36 and 1.29 μg/ml and 1, 1, 1, 1 and 12 h for the commercial suppositories and those containing 0, 5, 6 and 8% polycarbophil, respectively. The data indicate that as the polycarbophil concentration increased from 0 to 5% in the polyethylene glycol suppositories, the plasma levels and bioavailability improved significantly ( p < 0.1, Student's t-test), whereas on increasing from 5 to 6 and 8% the plasma levels and bioavailability decreased significantly ( p < 0.05). At 8% polycarbophil concentration, sustained release suppositories were produced but a decrease in plasma levels was observed.

Preparation and Evaluation of Sustained release Indomethacin Nonpareil Seeds

AbstractA controlled release oral drug delivery system of Indomethacin was developed using nonpareil seeds as a matrix system. These seeds were coated with different concentrations of drug release controlling materials viz Eudragit RL100 and Eudragit RS100, and bees wax. The particle size of the seeds and the concentration as well as the type of the drug release controlling Eudragits has a pronounced effect on the release rate profile of Indomethacin. All types of formulations showed release rate pattern which can be described by both first-order and diffusion controlled mechanism.

Release kinetics of drug from different combined ratios of micropellets.

Release behaviours of different combined ratios of fast-release (FR) and sustained-release (SR) micropellets were studied. The release kinetic of the combined ratios of theophylline micropellets system was found to be a Higuchi matrix release model, and a linear regression was found between the release rate and the combined ratio of FR and SR theophylline micropellets. However, the combined ratio of the indomethacin micropellets system was found to be an apparent zero-order release kinetic and a quadratic regression was obtained between the zero-order release rate and the combined ratios of FR and SR indomethacin micropellets. This different release behaviour might be due to the different type and concentration of coating solution used.

Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.

Preparation and dissolution characteristics of indomethacin sustained release beads

AbstractIndomethacin is a nonsteroidal anti-inflammatory agent and has a short half life, and causes gastric irritation. Sustained release beads of indomethacin were prepared and dissolution profiles were investigated. Beads were prepared by allowing drops of a suspension of the drug and excipients in a solution of cellulose acetate phthalate to drop into an acetic acid solution by means of a peristaltic pump. In a previous study1, sulfadiazine was used as a model drug to prepare beads by a similar method and the effects of various viscosity agents on the properties of these beads were assessed. Glycerin, polymers (Methocel and Avicel), and surfactants (Tween 80 and Span 80) were used as excipients. The incorporation of various viscosity agents and polymers into the suspension yielded beads with different disintegration and dissolution values. A high performance liquid chromatography method showed no indication of drug degradation during the preparation. The dissolution studies of the indomethacin prepara...

The Effect of Phenylpropanolamine on 24-Hour Blood Pressure in Normotensive Subjects Administered Indomethacin

We evaluated the effect of phenylpropanolamine hydrochloride (PPA) in 14 young, healthy, normotensive women who concurrently received indomethacin. Subjects received sustained-release (SR) indomethacin 75 mg bid and were randomly assigned to receive double-blind SR PPA 75 mg/d or placebo for four days. After a six-day washout period, subjects were crossed over to the opposite four-day double-blind treatment. Following an additional six-day washout period, subjects received indomethacin placebo and PPA placebo during a final, single-blind four-day period. Twenty-four-hour blood pressure (BP) monitoring every 30 minutes and a 24-hour urine collection for prostaglandin E2 (PGE2) were performed on the fourth day of each treatment period. Compliance with the medication regimen was confirmed by drug concentrations, pill counts, and urinary PGE2 concentrations. Compared with the indomethacin and placebo treatment periods, the combination of indomethacin and PPA had no significant effect on mean systolic or diastolic BP during the 24-hour study period or during any four-hour interval. We conclude that the combination of SR PPA 75 mg/d and SR indomethacin 150 mg/d for four days has no adverse effect on BP in normotensive women.