Study And Application Of Functional Ion Exchange Resin On Pulsatile-release Capsules And Lung-Targeting Injectable Microspheres Drug Delivery Systems

As a new kind expedient, ion exchange resin had been used in liquid controlled-release dosage form widely. Adding functional groups to the ion exchange resin could extend the application of ion exchange resin in pharmacy. The sodium polystyrene sulfonate and the chitosan were used as the raw materials to prepare the functional ion exchange resin-pH-sensitive ion exchange resin and biodegradable ion exchange resin. And then diltiazem hydrochloride and bromhexine hydrochloride were used as model drug to make the diltiazem hydrochloride pulsatile-release capsules and bromhexine hydrochloride lung-targeting injectable micropheres. And then the pharmacokinetics study of the diltiazem hydrochloride pulsatile-release capsules in beagle dogs and the tissue distribution study of the bromhexine hydrochloride lung-targeting injectable micropheres in rats were carried out. Research work was composed of the following parts:Part 1. Preparation of the pH-sensitive ion exchange resin and the diltiazem hydrochloride pulsatile-release capsules1. pH-sensitive ion exchange resin was synthesized by the microemulsion polymerization and the sulfonation reaction with SDS as emulsifying. Microspheres of this resin were characterized by FTIR. The results showed that the pH-sensitive ion exchange resins were successfully prepared with the particle size in 10 ~ 100 μm. The basic physical and chemical characters (water content, wet density, particle size, swelling, heavy mental content) of the pH-sensitive ion exchange resin were investigate according to the BP. With the mice and the cat as the test objects, the acute toxicity and the pharmacology test of the pH-sensitive ion exchange resin were carried out. The results showed that the pH-sensitive ion exchange resin had good compatibility with the animal.2. The diltiazem hydrochloride pulsatile-release capsules were made by bath method. The results showed that the exchange speed of the pH-sensitive ion exchange resin was faster than the traditional ion exchange resin and the drug content declined; with the increasing of temperature, the exchange speed faster and the drug content ascended; with the increasing of the concentration of drug solution, the exchange speed faster and the drug...