Optimization Of The Preparation Of New Permeable Polyacrylic Resin And Its Performances Investigation

As possessing the merits of high performance,low toxicum and convenient to take along, the development of new dosage forms for slow-release and controlled-release preparation had been paid more and more attention to. Early in the 1970s, the slow-release and controlled-release preparation and the corresponding materials had been researched. There are many kinds of materials available for preparing slow-release and controlled-release preparation, among of which, the acrylic resin has been widely used as the coating and matrix materials of medicine in pharmaceutical industry. The Eudragit series made by the Rohm Pharma occupied the market, which are expensive, while the domestic products are limited to use because the properties lack stability. We aim to improve the deficiency of the available products and to develop new type of acrylic resin which is stable, widely used, low costly and convenient for application. Liq-Bulk polymerization has been used to prepare an additional product of Eudragit RL/RS, the solid, which the temperature of glass-transition (Tg) was low and the permeability was mediate had been made through facts analysis and orthogonal experiments. Its performance indexes were corresponded to correlative standards of pharmacopoeia. The modeling medicine was prepared as slow-release coating tablets and slow-release matrix tablets, which putted in use as verification of acrylic resin on the release effects by cumulative release experiments.Methods:It utilized MMA, EA, BA and DMC as the polymerization monomers, AIBN as the initiator, dehydrated alcohol as the solvent, transformation efficiency of monomers as the index in facts analysis experiments and relative molecular mass distribution as the index for orthogonal experiments. We researched on effects with different dosages of solvent, initiator and the temperature as the facts in the orthogonal experiments to get an optimal condition of synthesis. And the performance indexes were corresponded to correlative standards of pharmacopoeia. Potassium Citrate was adopted as the modeling medicine separately to produce slow-release coating tablets and slow-release matrix tablets, which putted in use as verification of acrylic resin on the release effects by cumulative release experiments.Results:(1)Optimal synthesis conditions are as follows: solvent 30%, initiator 0.3%, temperature 60-70-80℃, in which stages lasts 1h,4h and 1h respectively, and the whole progress lasted about 6h, which was shorter than before and energy saved.(2)The self-made polyacrylic resin, of which Mn=26695,Mw=76588,relative molecular mass distribution was 2.87,Tg was 26.86℃, the base number was 21.96mg/g, and the dynamic viscosity, monomer residue, loss on drying, residue on ignition, heavy metal and arsenic salt were compliance with correlative standards of pharmacopoeia, among which the monomer residue had decreased from <0.4% to <0.06%.(3)The self-made polyacrylic resin was employed as the coating material to produce the Potassium Citrate slow-release tablets, which were zero order released by polyacrylic resin 5g/100gPC, talc 0.37g/100gPC. Compared to Eudragit RL/RS, application of self-made polyacrylic resin is without plasticizer, simpler composition and less cost.(4)The self-made polyacrylic resin was also employed as the matrix material to produce the Potassium Citrate slow-release tablets which coincidenced to Higuchi equation. The formula was composed by matrix 50%(w/w), Lac and MCC 5%(w/w), 10%PVP (80% alcohol solvent) as the binder, and the pressure was between 10-12kg.Conclution:Liq-Bulk polymerization had been used to prepare an additional product of Eudragit RL/RS. Compared to the traditionary bulk polymerization, it could avoid regional explosive polymerization efficiently. The temperature of glass-transition (Tg) was low and the permeability was mediate of the self-made polyacrylic resin, which could be employed as the coating material to prepare slow-release coating tablets without plasticizer, and as matrix materials to prepare slow-release matrix tablets. Its performance indexes were corresponded to correlative standards of pharmacopoeia.