The meaning of sustained release technology

Sustained-release pharmaceutical preparations can effectively reduce the frequency of taking drugs, reduce the side effects of drugs and reduce the total amount of drugs, which is in line with people's medication habits. Because of its short development cycle, low investment, rapid development, increased technical content and significantly increased added value, it has attracted much attention. With the rapid development of science and technology, the emergence of new excipients, new materials and new processes and the modification of drug carriers provide a broad space for the exploration and development of sustained-release preparations.

1 matrix sustained and controlled release preparation

Skeleton technology refers to making drugs and one or more inert solid skeleton materials into tablets, granules or other forms of preparations by pressing or melting technology, which are often used as skeleton tablets. Generally speaking, according to the different materials used to prepare the skeleton, it can be divided into the following four types:

1. 1 insoluble matrix sustained/controlled release tablets are made of water-insoluble or extremely water-soluble polymers or nontoxic plastics. Commonly used insoluble skeleton materials are EC, polyethylene, polyvinyl chloride (PVC), polypropylene and so on.

1.2 hydrophilic hydrogel matrix sustained/controlled release tablets are one of the main types of oral sustained/controlled release preparations at present, accounting for about 60% ~ 70% of the matrix tablets on the market. Drug release process is a comprehensive process of matrix dissolution and drug diffusion. Many hydrophilic polymer materials (such as methylcellulose, HPMC, etc. ) can be used as skeleton material.

1.3 slow/controlled release tablets based on wax, that is, bio-dissolution matrix tablets, release drugs through the gradual dissolution of wax or ester. Commonly used shelf materials include stearic acid, carnauba wax, beeswax and hydrogenated vegetable oil.

1.4 mixed material matrix sustained/controlled release tablets are made by mixing drugs with two or more insoluble waxes and hydrophilic gel matrix materials. In recent years, some new carriers made of skeleton sheets have also appeared. For example, Pengmei et al reported that biodegradable gelatin gel can be obtained by mixing L- lactic acid oligomer grafted gelatin with gelatin, so as to realize the slow release of simvastatin insoluble in water, solve the biocompatibility problem of the remaining materials after drug release, and provide broad potential for water-insoluble drugs. Sirpa et al. used D, L- lactic acid (SPDLA) polymers with different molecular weights as excipients to prepare theophylline oral sustained-release matrix tablets. In vitro studies show that drug release depends on the molecular weight of SPDLA polymer. With the increase of molecular weight of SPDLA, the matrix tablets with longer dissolution curve (up to 8- 10 hour) can be obtained. In addition, the prolongation of drug release has nothing to do with the pH value of dissolution medium, which proves that SPDLAs is a new drug carrier polymer suitable for oral drug controlled release system. Zhou Yanling et al. used mesoporous 58S bioactive glass (m58S) as anticancer drug carrier, and evaluated its loading capacity and release performance of epirubicin [4]. The experimental results show that the drug loading capacity of m58S for hydrophilic drug Epirubicin is 40%, which is more than three times that of ordinary sol/gel 58S bioactive glass, and it has the characteristics of long-term sustained release. Mesoporous bioactive glass drug delivery system loaded with anticancer drugs can repair bone tissue and release anticancer drug molecules continuously, which is expected to become a new treatment method for bone tumors.

2 film coated sustained/controlled release preparation

Coating technology is also one of the most commonly used and effective methods to prepare oral sustained-release preparations. Tablets, granules, pills and even pharmaceutical powders can be coated. Commonly used film coating materials include cellulose acetate, EC, polyacrylate, PVA and so on. Waterborne coating technology is an important development direction of film coating. At present, the coating technology of polymer aqueous dispersion is developing rapidly, and there are more and more kinds of coating materials, such as polyacrylic resin aqueous dispersion, EC aqueous dispersion (Aquacoat and Surelease), cellulose acetate emulsion and so on. Wang took high amylose corn starch with abundant natural resources and good biocompatibility as the research object, and obtained modified starch with good acid resistance and enzymolysis resistance through physical recombination and enzyme modification technology. The membrane-controlled pellet delivery system constructed by using it as the carrier material of water-dispersible film coating has good drug controlled release performance, which can protect the physiological activity of drugs, prolong the drug release time and improve the drug delivery effect. This will lay a foundation for starch as a water-dispersible coating film to meet the sustained and controlled release of drugs in digestive tract.

3 osmotic pump controlled release preparation

Osmotic pump technology is a technology that uses osmotic pressure difference as driving force and combines with semi-permeable membrane to control drug release. At present, osmotic pumps are widely used. Osmotic pump tablets are composed of drugs, osmotic active substances and propellants. And is wrapped with a semipermeable membrane with drug release holes. Oral osmotic pump tablets have attracted people's attention because of their unique release mode and stable release rate. It is the most widely used osmotic pump preparation and the most ideal oral controlled release preparation so far. Its advantages are that drug release can be controlled by zero-order kinetics, and it is basically not affected by physiological conditions such as gastrointestinal pH, enzymes, gastrointestinal peristalsis and food. Can obtain a higher release rate, avoid or reduce the fluctuation of blood drug concentration to the maximum extent, and reduce the toxic and side effects; At the same time, the drug release rate can be well predicted and designed, and there is a good correlation in vivo and in vitro. In addition to the traditional single-chamber osmotic pump tablets and double-chamber osmotic pump tablets, there are many new technologies, such as three-layer osmotic pump tablets, extrusion osmotic pump that can control the release of nifedipine for 24 hours, effervescent osmotic pump tablets to prepare traditional Chinese medicine compound preparations and so on.