Study On The Preparation And Characteristics Of Molecularly Imprinted Polymers For Sulpiride

Sulpiride is a benzamide drugs that is used as an antipsychotic, which is effective in the treatment of stupor, withdrawal, hallucinations, delusion and mental disorder. It also has a role in antidepressant and central antiemetic. Recently,the molecularly imprinting technology (MIT) has recently arisen increasing attention, and various molecularly imprinted polymers (MIPs) has been prepared in many fields. MIPs are synthetic polymeric materials possessing specific cavities designed for a target molecule, which have specific recognition and selective adsorption to the molecular template and their structural analogues. As its unique advantages, it has been widely used in separation, solid phase extraction, controlled release drug delivery system, enzyme catalysis simulation, etc.In this research, the MIPs of sulpiride was prepared by classical bulk polymerization method using methacrylic acid (MAA) and itaconic acid (ITA) as functional monomer, respectively. In order to obtain the optimum experimental conditions, the influence factors of preparing the MIPs were investigated for their adsorption properties, and then the structure of the MIPs optimized was characterized. The mechanism of MIPs obtained on the specific recognition and adsorption for sulpiride was also discussed. MIPs have been applied to the specific recognition and release characteristics in preliminary study used as carriers. All of this laid the foundation for further study in the separation and enrichment, and sustained release formulation materials for sulpiride. The research in this paper was carried out as following: 1. The MIPs of sulpiride was prepared by bulk polymerization method with MAA as functional monomer under the optimized experimental conditions. The optimum conditions were as following: 0.3 mmol sulpiride, 1.2 mmol MAA, 6 mL acetonitrile, then the obtained polymer after polymerization was eluted with methanol–acetic acid (9:1). The adsorptivity of the MIPs were measured by the static absorption test, and its structure was also characterized through Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The obtained results showed that the MIPs had higher specific recognition capability to sulpiride, and its imprinted factor value was 3.77. The characteristic of adsorption kinetics of MIPs showed that adsorption ratio could achieve 88% within 10 min. Its maximum adsorption capacity reached 178.39μmol/g based on Scatchard simulation results. It was further found that imprinting sulpiride for MIPs appeared inhomogeneous with two different types of specific and non-specific binding sites. FTIR spectra proved that the primary binding site in the MIPs was structurally hydrogen bonding formed between carboxyl group of MAA and amide group of sulpiride. The results of SEM indicated that the particles of the MIPs were much smaller, larger surface area than its non–imprinted polymers (NIPs).2. The sulpiride MIPs was prepared by bulk polymerization method with ITA as functional monomer, afterwards the experimental conditions was optimized, and then the adsorption properties of MIPs obtained were also measured through static absorption experiment. The structure of the MIPs was also investigated by means of FTIR and SEM. The results showed that the optimized conditions of preparing the MIPs were as follows: 0.3 mmol sulpiride and 1.2 mmol ITA were dissolved in methanol, then 4.5 mmol EDMA and 60 mg AIBN were added together for polymerization 24 hours initiated by heating. The MIPs indicated a higher specific recognition capability with imprinted factor 5.58, and its nonspecific adsorption capacity was greatly reduced comparing with the MIPs prepared by MAA as monomer. The MIPs exhibited a quick absorption rates to sulpiride, which adsorption ratio could reached 80% within 10 min, the Scatchard simulation results also showed that their binding sites was inhomogeneous. The characteristics spectra of FTIR for the MIPs also proved that ITA and sulpiride was bonded through hydrogen bonds. The results of SEM indicated that the particles of the MIPs were much smaller, larger surface area than its non–imprinted polymers (NIPs).3. The selectivity of MIPs prepared with MAA and ITA as monomer was evaluated using the static absorption experiment, in which the analogs of sulpiride such as amisulpride and tiapride were chosen as the substrates. Based on the chemical structure of sulpiride, p-toluenesulfonamide, formamide and 1-methylpyrrolidine selected as substrates to investigate recognition mechanism of the MIPs. The results to the analogs revealed that using ITA as monomer exhibited higher selectivity; its selectivity factor was much larger than MAA. Through the adsorption test for several substrates composed of sulpiride, the results of their adsorptivity showed in following descending order: formamide>1-methylpyrrolidine>p-toluenesulfonamide, which proved that oxygen atom and nitrogen atom in the amide group were the main recognition sites and nitrogen atom in the 1-methylpyrrolidine was second. The MIPs prepared by ITA as special carrier was applied to recognize sulpiride from a mixture composed with sulfonamides, phenylamines, dicarboximides and sulpiride. The results showed that the MIPs has higher selectivity due to its specific recognition ability to sulpiride except TMP, therefore it can be used as separation and enrichment matierals.4. For further application of MIPs, Drug-loaded MIPs and Drug-loaded tablet made by some excipients using the MIPs as carrier material to carried out release test. The results indicated that the release of sulpiride in pH 6.8 simulated intestinal fluid could be equilibrium within 100 min when using MIPs as carriers; the tablet pressed sulpiride reached equilibrium within 250 min with certain controlled release property. Thus the MIPs will be potentially valuable for development of drug delivery materials.