The Preparation Of Indomethacin EL100-55 Enteric Nanoparticles

ObjectiveIndomethacin(IDM),a non-steroidal anti-inflammatory agent acts by inhibiting cyclo-oxygenase(both 1 and 2)non-selectively,is used worldwide for its analgesic,antipyretic and anti-inflammatory.For example,rheumatoid arthritis,ankylosing spondylitis,osteoarthritis and acute gout.Since the indomethacin formulation of the traditional oral dosage form can lead to elevated blood pressure,decreased renal function and even gastric ulcer,a new drug delivery system that reduces both side effects and reduces its efficacy is one of the clinical problems to be solved.The study for indomethacin nanopaticle system emphasizes on pH dependent EL100-55 as carrier material for preparing enteric nanoparticles,combing with pharmacokinetic and pharmacodynamic evaluation results to reduce indomethacin on the digestive system irritation.A novel drug delivery system is the ultimate need that minimize adverse effects.MethodsIn this study,the pH-dependent materials EudragitL100-55 were used as drug carrier and indomethacin as model drug.Paticle size(PS),entrapment efficient(EE)and drug loading(DL)were used as independent variables with the ratio of drug to enteric materials and PVA as the dependent variable.Formulation was optimized and prepared via the central composite design method.The enteric solution was prepared by solvent evaporation method.Bag filter method was used to study the release characteristics in vitro.The process of small intestine absorption and pharmacokinetic character was described by pharmacokinetic experiment in SD rat.Kunming mice were gavaged for 5 days,then the model of inflammation and pain were established.Study the effect of indomethacin enteric-coated nano-solution on anti-inflammatory and analgesic.The degree of damage to the organs of mice was evaluated by the experimental method of pathological sections.ResultsThe results of the prescription optimization showed that the 0.5mg/mL enteric-coated nanoparticles were prepared with the dosage of EL100-55 92 mg and 1% PVA,which had the best characterization.The PS,EE,DL and PDI were 163.7nm,92.30%,4.76% and 0.233,after repeated experiments showed that the results of optimization theory and actual values lower than 2%.FTIR,XRD and DSC showed that indomethacin and enteric material did not react,no new substances were found,and the drug substance was encapsulated by enteric material.In vitro released test results show that the suspension in the artificial gastric fluid release little with the time,but the cumulative release reach less than 50% while enteric-coated nano-solution in the artificial gastric almost release none,when transferred to the artificial intestinal the release significantly increased up to 80%.In the rat intestinal absorption experiment,the absorption coefficient of the enteric-coated nanoparticles group was 0.1371,while the control group was 0.0446,the absorption of the control group was significantly smaller than that of the enteric-coated nano-particles group.And pharmacokinetics in rats indicated that nano-solution can significantly improve the bioavailability of resveratrol in rats.Mice pharmacodynamics experiments show that low and high-dose group of enteric-coated nano-solution can inhibit ear swelling,reduce body pain,improve pain tolerance.While in the suspension group reflects a certain degree of analgesic anti-inflammatory effect.The histopathological changes of the mice were observed in the normal physiological state.Compared with the tissues of the enteric group and the suspension group,the edema pattern of the stomach was obvious in the suspension group.Conclusion1.The particle size of indomethacin enteric-coated nanoparticles prepared by solvent evaporation method is 100-200 nm,while not only the physical characterization is good but the reproducibility is high.2.Using the central composite design method optimize the most reasonable prescription.This method can reduce the number of experimental exploration and improve the experimental accuracy.3.The experimental results show that indomethacin enteric-coated nanoparticles can effectively combat inflammatory conditions,achieving better treatment to reduce the effect of pain.In vivo the absorption rate is fast with high bioavailability.4.Indomethacin enteric nanoparticles improved the bioavailability of the body at the same time and avoided the common destruction of the indomethacin for the stomach.While in the clinical application reduced the emergence of adverse reactions.