Construction And In Vivo /in Vitro Evaluation Of S-ibuprofen Oral Liquid Controlled Drug Release System

S-ibuprofen（S-IB）is the dextro-isomer of ibuprofen,a kind of non-steroidal anti-inflammatory drugs.It is recommended as preferred antipyretic and anti-inflammatory drug for children by WHO and FDA.However,S-IB is a kind of insoluble drug,and its solubility in body fluid is very low.Therefore,the dosage of S-IB is large and the conventional dosage form is not convenient for children to take.And the t_1/2/2 of S-IB is only 1-2hour,patients need to take3-4 times a day to maintain the treatment concentration.Frequent administration can lead to excessive fluctuations for blood drug concentrations,and increase irritation and adverse reactions to gastrointestinal tract.The research can be divided into the following five parts:Part Ⅰ Preparation of Drug Fiber ComplexFirstly,the insoluble drug S-IB was prepared into soluble S-IB sodium salt for ion exchange reaction,then ZB-2 strong basic anion exchange fiber was used as the drug carrier to prepare Drug-fiber complex（DFC）by bath and column method,respectively.The influence of fiber size,drug concentration,temperature and other factors on drug loading process was studied.The rate and equilibrium of ion exchange reaction between drug and fiber under different conditions were investigated,and the optimum process for preparing DFC was established.Part Ⅱ The bonding mechanism and in vitro release studied for DFCIt was confirmed by SEM and DSC that S-IB and fibers were chemically bound by ion exchange reaction rather than physical adsorption.In this chapter,the effects of pH、dielectric ion type,ionic strength,temperature and rotational speed on the drug release from DFC were investigated.f₂ similarity factor analysis was used to analyze and evaluate the in vitro release behavior of DFC,which provided theoretical and experimental basis for further preparation of sustained-release suspension.Part Ⅲ Study on coating technology and prescription for DFCThe DFC was firstly impregnated to avoid the burst drug release caused by the swelling of DFC in aqueous suspension,and then coated by emulsion-evaporation method.Referring to the ChinesePharmacopoeiaabout the dissolutiondeterminationmethod ofibuprofen sustained-release capsules,the prescriptions and technological factors in the process of coating were optimized.Finally,the type and dose of plasticizer,coating materials,curing temperature and time et al were definitely settled.DFC coated microcapsules were prepared with obvious sustained-release effect.The drug release behavior of DFC coated microcapsules followed the first-order kinetics process,membrane-controlled release was the dominant and particle diffusion was supplementary.Part Ⅳ Preparation of S-IB sustained-release suspensionBased on the sedimentation ratio and redispersibility,the formulation and technology were screened out to make the suspension has good physical and chemical stability.The in vitro release behavior of S-IB coated microcapsules and sustained-release suspensions showed that the suspension medium had no significant effect on drug release.The influencing factors and accelerated tests of S-IB sustained-release suspension were carried out.The redispersibility,sedimentation ratio,drug leakage,drug content and in vitro release behavior were investigated to evaluate the stability of S-IB sustained-release suspension.The results showed that the stability of S-IB sustained-release suspension was well and met the requirements.Part Ⅴ Pharmacokinetics studies of S-IB Sustained Release Suspension in RatsIn this chapter,the in vivo analysis method of S-IB sustained-release suspension in SD rats was established.The specificity,precision,method recovery and extraction recovery of the method all met the requirements.The rats were given S-IB suspension and S-IB sustained-release suspension respectively by intragastric administration to investigate the pharmacokinetics by non-compartment model.According to the pharmacokinetic parameters,the C_maxax of S-IB sustained-release suspension was decreased and the T_maxax was prolonged compared with S-IB suspension.The t_1/2/2 was 6.926 h and 2.356 h,respectively.The results showed that S-IB sustained-release suspension could effectively stabilize the blood concentration of drugs,and the sustained-release effect was obvious in vivo.The relative bioavailability of S-IB sustained-release suspension to commercial suspension was 114.70%,which was bioequivalent.