Indomethacin Microspheres Research Articles

Development and Evaluation of Indomethacin Parenteral Delivery of Microspheres for the Treatment of Gout

Gout is a disease caused by the deposition of monosodium urate (MSU) crystals in tissue such as cartilage, synovial membranes, bones and skin which causes inflammation in the synovial tissue. Indomethacin is first line of drug used as NSAID for the treatment of Gout. The aim of this study was to encapsulate Indomethacin in ethyl cellulose microspheres and compare the efficiency of the formulated Indomethacin microspheres with the Marketed formulation. Indomethacin microspheres were prepared by solvent evaporation method. FTIR studies revealed there was no significant interaction between the drug and polymer. Preformulation studies gave satisfactory results. SEM studies showed a spherical smooth microsphere average size of 10.4±3.04. The percentage entrapment efficiency and percentage drug release after 10 hours was found to be 82.97±1.6 % and 52.04±0.58 % respectively. The therapeutic effect of the Indomethacin microspheres was evaluated by the swelling of knee joints, joint range of motion and histologic analysis of MSU induced rat model. The prepared indomethacin microspheres showed effective prolong in the retention time of the drug in the intra articular cavity to 30 d which is more than that of the marketed formulation. Intra- articular injection of Indomethacin microspheres efficiently relieved inflammatory symptoms such as swelling index, joint range motion and suppressed inflammatory cell infiltration than the marketed formulation. Thus intra-articular injection of Indomethacin loaded microspheres proved to be a promising therapeutic method in the treatment of Gout. Keywords: Gout, indomethacin, ethyl cellulose, microspheres, inta-articular

English

English

PEG-derivative effectively modifies the characteristics of indomethacin-PLGA microspheres destined to intra-articular administration

The aim of this study was to obtain biodegradable indomethacin microspheres for intra-articular administration in rheumatoid arthritis, where angiogenic processes are involved. Indomethacin concentrations to achieve an anti-angiogenic effect would be five-times higher than an anti-inflammatory. Microspheres were prepared by solvent evaporation using PLGA. Indomethacin is a poor water-soluble drug with it being possible that dissolved and non-dissolved drug co-exist within the polymeric matrix resulting in rapid release. To control this release, an oil-PEG-derivative was incorporated, producing changes in morphology, crystallinity and indomethacin release. To minimize the amount of microspheres administered, a two-factor five-level central rotable composite 22 + star design was employed with two independent variables: indomethacin percentage and PEG-derivative percentage. The optimum formulation showed mean encapsulation efficiency of 94.3 ± 2.2% and released 7.99 ± 0.25 µg indomethacin/day/mg microspheres for 21 days. A dose of 20–50 mg of this formulation could be appropriate to achieve both anti-angiogenic and anti-inflammatory effects. Preliminary cytotoxicity studies performed in rat splenocytes showed an adequate cell viability.

Extended release lipophilic indomethacin microspheres: formulation factors and mathematical equations fitted drug release rates.

Extended release liphophilic microspheres of indomethacin were prepared using cetostearyl alcohol (CsA), stearyl alcohol (SA) and cetyl alcohol (CA) in the various drug-lipid ratios. The release of indometacin was studied on the basis of USP criteria and the effects of drug-lipid ratio, the size of microspheres and carboxymethylcellulose sodium (CMC-Na) added as a hydrophilic polymer on the drug release were investigated. In vitro dissolution studies were performed using USP XXIII apparatus I at pH 6.2. Release profiles were evaluated according to first order, Higuchi square root of time and Hixson-Crowell cube root models. The best fit was found with the square root of time model (r2=0.991) for the microspheres (125-250 microm) prepared in 1:4:1 drug-lipid-copolymer ratio using stearyl alcohol. With a further regression analysis, an excellent equation (Release%=-10.721+42.549*square root of (t)-4.027*t) was developed for empirical drug estimation (r2=0.998).

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.

Bioavailability of controlled release indomethacin microspheres and pellets

The plasma and urinary phannacokinetics of controlled release indomethacin microsphere and pellet formulations have been compared after repeated oral administration. Statistical analysis, using the one-tailed independent mean sample t-test, indicated that the microsphere formulation exhibited a trend for greater relative systematic availability (0.25 > P > 0.20) and showed a longer time to reach maximum plasma concentration ( t max) than the pellet formulation ( P < 0.005).

Controlled release indomethacin microspheres prepared by using an emulsion solvent-diffusion technique

The feasibility of producing controlled release indomethacin microspheres, with acrylic polymers Eudragit RS and RL, by employing two emulsion solvent-diffusion systems, is compared. Microspheres with various polymer/drug ratios and polymer combinations (Eudragit RS/RL ratios) were prepared. The physical properties, loading efficiency and dissolution behaviour depended on the emulsion solvent-diffusion technique, polymer/drug ratio and polymer combination. The drug release is described on the basis of two bi-exponential, first-order models.

CORRELATION BETWEEN GASTRIC IRRITANCY AND BIOAVAILABILITY OF INDOMETHACIN MICROSPHERES

Indomethacin microspheres were prepared by an emulsion solvent evaporation method. Ethylcellulose was used as the matrix material at 1:1 drug/polymer ratio. The prepared microspheres was tested for drug content, dissolution characteristics, anti-inflammatory effect in rats and for their possible gastric effect in rabbits .A controlled release pattern of the medicament was found to be existed from the prepared microspheres. The prepared microspheres gave an anti-inflammatory effect in rats as that produced by the intact medicament. Histological examination of rabbit's stomach proved the superiority of the tested microsphere over the intact drug.

Design and release kinetic pattern evaluation of indomethacin microspheres intended for oral administration

Indomethacin has been incorporated into either ethylcellulose (EC) or Eudragit RL microspheres by a solvent-evaporation process. Production variables have been tested in an attempt to produce indomethacin microspheres having adequate oral controlled-release properties. In spite of high drug content in the ethylcellulose microspheres, the indomethacin release rate was too slow and incomplete. Although the addition of an hydrophilic polymer, polyethylene glycol), to the EC polymer enhanced the indomethacin release rate, it was not possible to reach release profiles suitable for oral use. Therefore, indomethacin was incorporated into a more permeable polymer, Eudragit RL. While incorporation efficiency decreased with increasing initial concentration of indomethacin, adequate oral-release profiles were achieved. It was found that all the global-release profiles yielded by the indomethacin-loaded Eudragit RL microspheres conformed to the Higuchi diffusional model of dispersed drug particles in spherical micromatrices and not to the desorption kinetic model of a dissolved drug from a monolithic spherical device.

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

AbstractMicrospheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.