Release Rate Of Indomethacin Research Articles

Phosphorous Containing Chitosan Beads for Controlled Oral Drug Delivery

Phosphorous containing chitosan (PCTS) was synthesized by a graft copolymerization technique in order to be used as controlled drug delivery devices. To test this potential, PCTS beads were prepared by using tripolyphosphate, at pH 4.0 and characterized by scanning electron microscopy. The in vitro drug release behavior in various pH solutions was studied using indomethacin (IM) as a model drug at two different concentrations (0.3 and 0.6% w/w). The release percent of IM from PCTS beads was found to be increased with the increasing of pH in the buffer solution. The release rate of IM at pH 7.4 was higher than that at pH 1.4, due to the ionization of phosphorous groups and the high solubility of IM in the alkaline medium. These results indicated that PCTS beads have the potential to be used as controlled drug delivery systems through oral administration by avoiding the drug release in the highly acidic gastric fluid region of the stomach.

Radiosterilisation of indomethacin PLGA/PEG-derivative microspheres: Protective effects of low temperature during gamma-irradiation

Currently, γ-irradiation seems to be a good method for sterilising drug delivery systems made from biodegradable polymers. The γ-irradiation of microspheres can cause several physicochemical changes in the polymeric matrix. These modifications are affected by the temperature, irradiation dose and nature of the encapsulated drug and additives. This study has aimed to evaluate the influence of temperature during the sterilisation process by gamma irradiation in indomethacin PLGA microspheres including a PEG-derivative. Microspheres were prepared by the solvent evaporation method from o/w emulsion and were then exposed to γ-irradiation. A dose of 25 kGy was used to ensure effective sterilisation. Some microspheres were sterilised with dry ice protection that guaranteed a low temperature during the process whilst others were sterilised without such dry ice protection. The effects of γ-irradiation on the characteristics of non-loaded PLGA/PEG-derivative and indomethacin loaded PLGA/PEG-derivative microspheres with and without protection were studied. Non-protected microspheres showed changes in their morphological surface, polymer glass transition temperature, molecular weight and release rate of indomethacin after sterilisation. However, microspheres sterilised with protection did not show significant differences after γ-irradiation exposure. The sterilisation method was satisfactory when the indomethacin loaded microspheres including a PEG-derivative were exposed to γ-irradiation at low temperature.

Release behaviors of porous poly(butylene succinate)/poly(ɛ-caprolactone) microcapsules containing indomethacin

The biodegradable poly(butylene succinate)/poly(ɛ-caprolactone) (PBS/PCL) microcapsules containing indomethacin were prepared by emulsion solvent evaporation method. The morphologies, thermal properties, and release behaviors of PBS/PCL microcapsules were investigated. As a result, the microcapsules exhibited porous and spherical form in the presence of gelatin as a surfactant. From the DSC result, the PBS/PCL microcapsules showed the two exothermic peaks meaning the melting points of PCL and PBS. The results of FT-IR and DSC proved that the PBS and PCL were mixed so that the PBS/PCL microcapsules were composed of two wall-forming materials. And the release rate of indomethacin from the microcapsules was decreased with increasing the PCL content. It was noted that an addition of PCL on the PBS led to the decrease of pore size in the PBS/PCL microcapsules.

Preparation and Clinical Application of Indomethacin Gel for Medical Treatment of Stomatitis

The preparation and clinical applications of indomethacin (IM) gel were investigated in the treatment of stomatitis resulting from chemotherapy and radiotherapy for cancer. IM gel was prepared by adding various water-soluble polymers [hydroxypropyl cellulose (HPC), etc.] to IM aqueous solution. The release rate of IM from IM gels was found to decrease with increasing polymer concentration and viscosity and to follow a first-order reaction rate equation. The release rate of IM from the IM gel with HPC was decreased gradually with increasing polymer concentration and to be easily controllable compared with gels with other polymers. The time before pain relief occurred after application of the IM gel was slightly shorter and the duration of pain relief was longer compared with the IM aqueous solution. It was confirmed that IM gel is useful in the treatment of stomatitis.

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.

Indomethacin release from ion-exchange microspheres: impregnation with alginate reduces release rate

Ion-exchange microspheres (MS) designed as a drug delivery system for embolization coupling ability to occlude vessels and chemotherapy were used to evaluate a manufacturing process allowing to control the drug release rate through reduction of diffusion rate of the drug within the particle by impregnation of calcium alginate inside the porous MS. Impregnation was performed by diffusion of sodium alginate inside DEAE-Trisacryl® MS, dispersion of the MS in deionised water and gelling alginate by adding CaCl 2 to the dispersed MS. Studied parameters were alginate concentration, alginate diffusion time and calcium concentration. Indomethacin was loaded into the MS by eluting an aqueous indomethacin solution through a chromatographic column packed with impregnated MS. Indomethacin loading was reduced by alginate. Swelling studies showed indomethacin loading enhanced the hydrophobicity of MS while impregnation had no effect. This had an incidence on indomethacin release rate, which was assessed using the rapid elution of PBS through loaded impregnated MS packed in a column. Indomethacin loading reduced its own rate of release. MS impregnated with 2% w/v alginate gelled with a 40 mM calcium solution presented the lower release rate. This work indicated the manufacturing conditions to display a calcium alginate matrix effect on indomethacin release from DEAE-Trisacryl® MS.

Thermal treating as a tool for sustained release of indomethacin from Eudragit RS and RL matrices

Eudragit RS and RL are biocompatible non-swelling polymers that widely used in the preparation of sustained release drug delivery systems. In this study, the effect of thermal treating on the tensile strength of tablets and release of indomethacin from Eudragit RS and RL matrices were investigated. The results showed that thermal treating at 40 °C has no effect on the release of the drug, whereas heat-treating at temperatures higher than 50 or 60 °C decreases the release rate of indomethacin from Eudragit RS or RL, respectively. It was shown that the duration of the heat treatment was also an important factor in controlling the release rate of indomethacin from Eudragit matrices. The results showed that an increase in the duration of the heat treatment from 2 to 24 h resulted in a reduction in the release rate of the drug. The heating of the matrices over 24 h had no significant effect on the release rate of indomethacin. It was shown that heat treatment of the matrices over the glass transition temperature of the polymer can prolong the drug release but had no significant effect on the tensile strength of tablets.

Improved Dissolution Rate of Poorly Soluble Drug by Incorporation of Buffers

This study focused on comparing dissolution rates of indomethacin after cocompressing with three different buffers (calcium carbonate, sodium carbonate, and sodium citrate) at pH 2 and 7. Factors affecting the dissolution rate were also examined, such as type and particle size of buffer and weight-to-weight ratio of drug to buffer. It was found that, at pH 7, the release rates of indomethacin with sodium carbonate (<74 μm, all proportions) and sodium citrate (<74 μm, 75% loading) at a 20-min test time were about 10-fold and 6-fold greater, respectively, than that of indomethacin alone. When the drug and buffer were compressed into tablets using a tableting machine, the release rates of indomethacin for the control, sodium carbonate incorporated (25% and 75% buffer loading), and sodium citrate incorporated (75% buffer loading) at a 15-min test time were 50%, 90%, 66%, and 67%, respectively.

Influence of phase transformation on indomethacin release from microemulsions

The release rates of indomethacin from microemulsions containing water, isopropyl myristate, lecithin, lysolecithin and alcohol are reported. Depending on the composition, the microemulsions transformed on contact with the release medium into emulsions, liquid crystals, or remained as microemulsions. The release rates, measured by monitoring the change in pH of an acceptor phase as the release system was diluted into it, were consistent with an interfacial barrier being the rate-limiting step for solute release. The release rates were found to be dependent on the size of the disperse phase after dilution with the release medium, and on the alcohol used in the formulation. Microemulsions that remained transparent after dilution produced rate constants lower than those that transformed into emulsions. The rate constant for the microemulsion that transforms into liquid crystals was not calculated because of the broad dispersion, but the percentage of drug released was much lower than those from the others systems. The release rates were too rapid to allow sustained drug release, while the release observed for the microemulsion that transformed into liquid crystals was consistent with the slow release required for drug delivery applications.

Methoxy poly(ethylene glycol) and ϵ-caprolactone amphiphilic block copolymeric micelle containing indomethacin. : II. Micelle formation and drug release behaviours

Amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) (MePEG) and ε-caprolactone ( ε-CL) was prepared by polymerization of ε-CL initiated with MePEG. MePEG/ ε-CL block copolymeric micelles containing indomethacin (IMC) were prepared by a dialysis method and evaluated as a novel drug carrier. The size of micelle formed was less than 200 nm, and the size distribution of the micelle showed a narrow and monodisperse unimodal pattern. Also, the micelles formed by a dialysis method exhibited spherical structures. The indomethacin content in nanospheres was about 42.2%, for those prepared using copolymer, having molecular weight of about 12 000 and polymer/IMC weight ratio of 1/1. A release rate of indomethacin from nanospheres was slow, and thus the release continued over 15 days. As the molecular weights of the copolymer and the amount of drug entrapped increased, the release rate decreased. These results indicated that the drug-loaded nanospheres could be useful as a novel drug carrier in injectable delivery systems for hydrophobic drugs.

Release kinetics of indomethacin from pressure sensitive adhesive matrices

Release properties of indomethacin (IDM) from pressure sensitive adhesive (PSA) matrices consisting of styrene-isoprene-styrene block co-polymer to pH 7.4 phosphate buffer solution were investigated and kinetically analyzed. The amount of IDM released was increased with increasing initial concentration of the drug in the PSA matrix. When the drug began to be saturated in the matrix beyond its solubility, no further increase in the released amount was observed. These results could be explained by there being little contribution of the crystalline drug in the PSA matrices to the release. On the other hand, decrease in the thickness of the PSA matrix caused marked increase in the release rate of IDM. The reason might be rapid direct release of the crystalline drug from the PSA surface to the buffer solution, and this was confirmed by scanning electron microscopic observation of the surface. Since these results could not be fully analyzed by T. Higuchi's or W.I. Higuchi's equation, a simple compartment model was designed. This model was adequate to describe all release profiles of IDM from the PSA matrices. Obtained kinetic parameters were consistent with the release mechanism described above.

Preparation and Characterization of the Micelle-Forming Polymeric Drug Indomethacin-lncorporated Polyfethylene oxide)-Poly(β-benzyl L-aspartate) Block Copolymer Micelles

To estimate the feasibility of novel containers for drugs, polyethylene oxide)—poly(β-benzyl L-aspartate) (PEO-PBLA) micelles were prepared by dialysis against water using different solvents. The solvent selected is very important because it drastically affects the stability of polymeric micelles. The critical micelle concentration (cmc) of the prepared micelles in distilled water was determined by a fluorescence probe technique using pyrene. Indomethacin (IMC) as a model drug was incorporated into the micelles by dialysis and an oil/water emulsion method. Characteristics of PEO-PBLA micelles without and with the physically trapped IMC in the inner core of the micelles (IMC/PEO-PBLA) were studied by dynamic light scattering and gel permeation chromatography/ HPLC as well as an in vitro release test of IMC from the micelles. For the PEO-PBLA block copolymers, N,N-dimethylacetamide (DMAc) was found to be the best of the solvents tested to form stable polymeric micelles with a narrow size distribution and avoid its aggregation, and the cmc of PEO-PBLA micelles thus prepared was determined to be ca. 18 mg/L in water. The diameters of PEO-PBLA micelles and IMC/PEO-PBLA micelles in number averaged scale were observed to be ca. 19 and 25-29 nm, respectively. The release study of IMC from IMC/PEO-PBLA micelles in various buffer solutions at the pH range from 1.2 to 7.4 at 37 °C revealed that the release rate of IMC from the micelles was increased by increasing the pH of the medium and indicated that the release rate of IMC from the micelles are controlled by the partition coefficient of IMC based on the pH of the medium and interaction between IMC and the hydrophobic portion of the micelles.

Buffer controlled release of indomethacin from ethylcellulose microcapsules

The rate of release of indomethacin from ethylcellulose microcapsules prepared by coacervation was studied using internal buffer, dibasic sodium phosphate (DSP), to increase the solubility of the core. The dissolution rate of the drug was determined in phosphate buffer solutions of varying pH and concentration. The role of the stagnant diffusion layer at the microcapsule surface was also evaluated by changing the mixing in the dissolution test. Indomethacin release was accelerated considerably with increasing amounts of DSP in the core. DSP increases the pH inside the microcapsules, thus enhancing the release of the acidic drug. Increasing bulk solution pH increased the release rate of indomethacin, the enhancing effect being more pronounced with buffered microcapsules. Neither increasing phosphate concentration of the bulk solution nor increasing mixing of the microcapsules influenced the rate of release of indomethacin from unbuffered capsules. With buffered capsules the increase in phosphate concentration of bulk solution prevented leaching out of internal phosphate increasing the release rate of indomethacin. The release of indomethacin also accelerated slightly with increasing mixing.

Slow-release indomethacin formulations based on polysaccharides: evaluation in vitro and in vivo in dogs

A series of sustained release formulations for the potent anti-inflammatory drug indomethacin were prepared by dispersing indomethacin in polysaccharide matrixes to form small microspheres. The matrixes comprised insoluble polycationic salts of polysaccharides such as, polygalacturonic acid, alginate, or carboxymethyl cellulose salts or Gantrezan (a copolymer of methyl vinyl ether maleic anhydride). The influence of the type of cation used to prepare the polymer salts and the type of polymer on the release rate of indomethacin from the microspheres was tested in vitro, and some formulations were examined in vivo in dogs. The pH of the medium was found to have a considerable influence on the in vitro release rate, the rate at pH 7.2 being much faster than that at pH 6.2 or 1.5. In vivo tests in mongrel dogs showed a big difference in plasma levels among the dogs, while the highest plasma levels were obtained after administration of the nonformulated product. Statistical treatment of the pharmacokinetic data for nonformulated and the formulated products showed no differences in T max , t 1 2 , k el, AUC and MRT. C ma obtained from the Ca-polygalacturonic acid salt formulation and the commercial product Indocin S.R. (Merck) were statistically significantly lower than the values of the non-formulated product. Since it is likely that this reduction would result in a lessening of side effects, we propose that our indomethacin formulation based on Ca-polygalacturonic acid salt would be suitable for further testing in human volunteers.

Application of an oily gel formed by hydrogenated soybean phospholipids as a percutaneous absorption-type ointment base.

We investigated the possibility of developing an oily gel formed by hydrogenated soybean phospholipids (HSL) as a percutaneous absorption-type ointment base. Liquid paraffin (LP) was used as the oil, and indomethacin (IM), ketoprofen (KP), flurbiprofen (FP) and ibuprofen (IP) were used as model drugs. IM did not dissolve in LP, but solubilized when heated with HSL at a concentration of about 1% with 15% HSL at 95 degrees C. IM gel was thus prepared as follows: IM and HSL were mixed, added into LP, capped tightly, heated in a water bath and cooled. The consistency of the gel increased with increasing IM concentration, indicating some kind of interaction between IM and HSL. The release of IM from the IM gel was faster than that from a preparation in which IM was mixed in gel at room temperature (Gel + IM). The release rate of IM from IM gel was proportional to IM concentrations up to 1%, but became constant above that. Permeation of IM through hairless rat abdominal skin from IM gel was higher than that from the Gel + IM. The permeation rate was proportional to IM concentrations in the range of 0.1 to 0.5% in 15% HSL gel. KP and FP also solubilized in gel when subjected to the same procedure as IM, and their release and permeation increased when they were formulated as gels. However, no evident improvement of permeation was observed in the case of IP, which had high LP solubility. It was suggested that HSL showed no enhancing effect, but solubilized IM, KP or FP, leading to high permeation from the gel. After 3 months' storage, the permeation rate did not change for 0.5% IM in 15% HSL gel, but decreased for 1% IM in 15% HSL gel. This indicates that in the case of 1% IM in 15% HSL gel, IM is in a supersaturated state immediately after preparation and then recrystallizes with time.

Controlled release of indomethacin by chitosan-polyelectrolyte complex: optimization and in vivo/in vitro evaluation

Chitosan gel beads containing indomethacin, an acidic drug, were prepared by a polyelectrolyte complexation of sodium tripolyphosphate and chitosan. The effects of the molecular weights of chitosan hydrolysates on the release and absorption rates of indomethacin from gel beads were examined. The release rates of indomethacin decreased with increasing of molecular weight and indomethacin content. A negative correlation was observed between the molecular weight and release rate constant ( r = −0.983). The release of indomethacin depended upon the dispersion of the indomethacin solid particles in the beads, as well as the porosity, tortuosity and surface area of the matrix. The plasma concentrations ofindomethacin after oral administration of chitosan gel beads to beagle dogs exhibited the sustained-release pattern. With increasing molecular weight of chitosan, the AUC and C max were decreased, while MAT was increased. A good correlation was observed between the molecular weight of chitosan or dissolution rate constant and the MAT or AUC. The results revealed that the chitosan gel beads composed of chitosan hydrolysate, of molecular weight 25 000, might be the best for the sustained-release preparation of indomethacin. It was suggested that the absorption of other drugs could be controlled by the proper selection of chitosan hydrolysate of optimal molecular weight and predicted from in vitro dissolution tests.

Studies on controlled release of indomethacin from PVA hydrogel

The polyvinyl alcohol (PVA) hydrogel containing 1-methyl-2-pyrrolidinone (MP) and sorbitol was preapred by the freeze and thaw method. The release rate of indomethacin from PVA hydrogel was used as a criterion for deciding the optimum formula of hydrogel using the computer optimization technique. The hydrogel of optimum formula was composed of PVA (10 w/v%), MP (0 w/v%), and sorbitol (40 w/v%) and the release rate of indomethacin was 1.981 μg/ml·min1/2.

The behaviour of various fillers in spheronized uncoated and film-coated granules containing slightly water-soluble indomethacin

The release of indomethacin from uncoated and film-coated spheronized granules was investigated. Granules containing indomethacin and various fillers were spheronized using a Calevaspheronizer. The characteristics of the granules and the release of indomethacin from them were examined. The fillers used in the granules were microcrystalline cellulose, lactose, glucose, calcium hydrogen phosphate dihydrate and maize starch. Marked differences were observed in spheronizing ability between the various fillers. It was most difficult to obtain perfect spheres with the crystalline fillers glucose and lactose. Spheronizing was best for granules containing maize starch or microcrystalline cellulose. Release from uncoated granules was very fast. In 10 min nearly 100% of the drug was released, whatever filler was used. The Spheronization process only affected drug release from granules containing microcrystalline cellulose as filler. It changed the apparent densities of granules only in the case of those containing glucose. The ethyl cellulose: hydroxypropylmethyl cellulose ratio affected the release rate of indomethacin from all granules film-coated using a fluidized-bed technique irrespective of the filler. As the permeabilities of the film fell the release rates also decreased. Spheronization of the core resulted in release rates of indomethacin differing from those in earlier studies on the release of indomethacin from unspheronized granules. Release of the drug was slowest from granules containing microcrystalline cellulose (some 30% in 8 h).

The Release Rate of Indomethacin from Solid Dispersions with Eudragite

AbstractThe coprecipitates were prepared by a solvent technique using Eudragit E as carrier and indomethacin as a model drug.X-Ray diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the physical state of the studied formulations. Up to 50% of indomethacin can be dispersed in an amorphous state in Eudragit E.The influence of the pH on the in vitro release of solid dispersions has been evaluated. Because of the good solubility of Eudragit E at pH 1.2 a fast dissolution rate of the drug was observed while a marked delay was noticed at pH 7.5 where the polymer is only permeable to water. At pH 5.8 the kinetics of drug release can be modulated by the drug/polymer ratio. The dissolution rate of the drug can be increased by decreasing its amount in the coevaporate.

Study on absorption of indomethacin from sustained-release suppositories containing hydrogenated soybean lecithin in rabbits.

The absorption of indomethacin (IM) from suppositories containing hydrogenated soybean lecithin (HL) after rectal administration in rabbits was investigated with the aim of producing sustained-release suppositories. The suppositories were prepared by the fusion method with IM, HL and Witepsol H-15 (H-15). The IM release rate from the suppositories (IM 10 mg, HL 200 mg, total weight 1 g) was faster than that of the control suppositories without HL. The release of IM from the suppositories (IM 10 mg, HL 300 mg or 350 mg) showed slow-release profiles. In absorption studies in rabbits, sustained-plasma levels of IM were obtained when suppositories having an HL content of more than 300 mg were administered. The suppositories composed of Witepsol E-85 (melting point approximately 43 degrees C), 10 mg of IM, and 200 mg of HL, showed slow-release profiles in the release test, but did not show sustained plasma levels of IM in the absorption test. These results indicate that sustained-release suppositories able to release IM gradually from the surface of the suppositories can be obtained when HL, IM and H-15, whose melting point is lower than body temperature, are used in the preparation of the suppositories, provided that the HL content is high enough in relation to IM.