In foreign countries, transdermal preparations have entered a stage of high development and technological maturity in the 1980s, and are the third-generation new drug formulations following oral and injection preparations. The technical principle is that the drug is absorbed through the human skin and then directly enters the blood to exert its effect. Once this kind of preparation appears, with its long-lasting and constant, and controllable blood drug concentration, it avoids the liver first-pass effect of the drug, improves the bioavailability, reduces or avoids the occurrence of side effects, and the route of administration is simple, the advantages of high patient compliance have attracted market attention. Its biggest feature is that the bioavailability and targeting of the drug are good, the dosage of the drug is greatly reduced, and the drug effect is more obvious.
The technical team with Dr. Danyi Quan as the core has accumulated rich experience in the development of transdermal controlled-release drug delivery formulations in advanced countries, and has mastered the world’s most advanced research and development procedures, experimental models, and core technologies and expertise in the production process. With technology, the most effective, safest and practical transdermal controlled-release drug delivery formulation can be developed in the shortest time. Based on his many years of practical experience, Dr. Quan took the lead in proposing and establishing five models for the development of transdermal controlled-release drug delivery formulations: optimal polymer material model, optimal penetration enhancer model, optimal formulation model, in vitro The correlation model of human skin and animal skin for transdermal experiments, and a model for predicting blood drug concentration in human body based on in vitro transdermal experiments. This is indeed the first of its kind among foreign counterparts. The technology platform based on these five models is mainly used in small molecule drug transdermal controlled-release drug delivery technology (also known as passive transdermal drug delivery technology). It is worth mentioning that the application of new polymer materials in transdermal controlled-release preparations is another major technological innovation. Using the same polymer materials with different molecular weights, as well as the respective characteristics of different properties and different types of polymer materials, through reasonable formulation design and special process, the transdermal controlled release formulation can achieve the expected sustained and controlled release effect. In addition, the use of new polymer materials has made new breakthroughs in increasing drug loading, increasing drug stability, improving drug diffusion and penetration, and enhancing the adhesive force of patches.
Due to the barrier function of the skin stratum corneum to the outside world, most macromolecular drugs cannot penetrate the skin. Therefore, the transdermal controlled-release drug delivery of macromolecular drugs is a more difficult technical challenge. Recently, the research and development team led by Dr. Quan has made a breakthrough in the technology of radiofrequency microchannel long-acting sustained-release transdermal drug delivery. The establishment of this technology (also known as active transdermal drug delivery technology) platform will have a major impact on the research and development of the transdermal controlled release of macromolecular drugs (such as proteins, peptides, polysaccharides, vaccines, nucleic acids and genetic engineering drugs) into preparations, and has broad market prospects.
Delivery Systems (Implantable Drug Delivery Systems) refers to sterile solid preparations made of drugs and auxiliary materials for implantation in the body, mainly subcutaneous implants. Implantation administration generally adopts surgical incision to implant the drug, or use a special syringe to introduce it, which is a new way of administration developed on the basis of arterial interventional therapy. The implant can continuously release the drug in the body, and it can be absorbed directly into the blood circulation by subcutaneous absorption to play a systemic effect. It can avoid the first pass effect of the liver and has a high bioavailability.
All components of the implanted drug delivery system are made of medical materials with good biocompatibility with human tissues. Its characteristics are as follows:
1. Eliminate peaks and valleys caused by intermittent drug delivery and uneven drug dosage, and can be used in specific the site of action is maintained at a constant rate.
2. Continue to release the drug and maintain the therapeutic concentration. A smaller dose can achieve the therapeutic effect.
3. The drug can be directly implanted and act on the target to avoid the side effects of other tissues in the body.
4. Avoid rapid metabolism of some drugs and prolong their half-life in the body.
5. Drugs that are difficult to be administered by other routes can be administered by implantation.
6. It can avoid the discomfort, injury and pain caused by certain dosage forms after administration. If there is a serious allergic reaction or side effect, it can be taken out quickly.
Inhalation is a new type of pharmaceutical dosage form. This type of medicine uses aerosol inhalation to treat asthma and so on. Such as Tiotropium Bromide Powder Inhalation, Budesonide Powder Inhalation, Menthone Inhalation, Cobite Aerosol Inhalation, etc.
Nanotechnology is the commanding height of strategic technology in the 21st century. It is a comprehensive technology system that conducts research and industrialization of materials at the nano-scale, and uses nano-scale materials for cross-research and industrialization. The main content of nanotechnology research is nanoparticles, nanostructures, nanomaterials and nanodevices. It is internationally recognized that 0.1-100nm is a nanometer-scale space, 100-1000nm is a submicron system, and less than 1nm is an atomic cluster. Nanospace is a relatively independent intermediate field between the macro and the micro.
The research of nanoparticles in the field of pharmacy predates the emergence of the concept of nanotechnology, and various nanocarriers such as nanoliposomes, polymer nanocapsules and nanospheres have been studied in the 1970s. The routes of administration involved include injection, oral administration and ocular administration. In the field of drug delivery systems, the size of nanoparticles is generally defined in the range of 1-1000nm. Obviously, this range includes submicron particles above 100nm. As far as current research is concerned, nanoparticles and related technologies in drug delivery systems are mainly used to promote drug dissolution, improve absorption, improve targeting, and improve effectiveness. In recent years, more attention has been paid to the study of nanosystems for biological macromolecular drugs. The role of transmission is based on the nanometer size range defined in the field of pharmaceuticals and the existence of drugs in nanocarriers in molecular states. The fundamental properties of drugs have not changed. Therefore, the essence of many researches is a certain distance from the scientific connotation of nanotechnology. Nanotechnology (the significance and prospects of not only nanoparticles) in drug delivery need to be further understood.
Commonly used solid dosage forms are powders, granules, tablets, capsules, dripping pills, films, etc., which account for about 70% of pharmaceutical preparations. The common feature of solid preparations is that compared with liquid preparations, it has good physical and chemical stability, lower production and manufacturing costs, and is convenient to take and carry; the pre-treatment of the preparation process undergoes the same unit operation to ensure uniform mixing and accurate dosage of the drug , And there is a close relationship between the dosage forms; the drug can pass through the physiological membrane and be absorbed into the blood circulation after it is first dissolved in the body.
3D printing preparations
The application of 3D printing technology in our country’s medical industry began in the 1980s, initially mainly used for the manufacture of three-dimensional medical models. With the development of precision medicine and personalized medicine, the application of 3D printing technology in the medical industry is becoming more and more extensive. From three-dimensional models, surgical instruments to living transplanted tissues, human organs, to medicines, 3D printing technology is gradually becoming mature.
The application of 3D printing in the pharmaceutical industry is also highly revolutionary. Especially in the production of small batches of drugs, each batch of customized drugs can have a specific dosage, shape, size and release characteristics, and ultimately it is possible to make the concept of personalized drug manufacturing a reality. The pharmaceutical industry is conservative, and is more inclined to determine the production process and formula design to ensure the stability of the product. The application of 3D printing in the pharmaceutical industry can completely change the production of medicines into individual designs. Now 3D printing has been used in the manufacture of oral dosage forms of medicines, and a series of formulated medicines containing multiple active ingredients have been produced. These 3D printed medicines have different geometric shapes and release characteristics. In particular, the technology can achieve precise dosages.
New type of sustained and controlled release formulations
Slow-release formulations refer to formulations that can continue to release the drug for a long time after administration to achieve a long-acting effect. For the preparations that automatically release at a predetermined rate and keep the blood drug concentration constant within the effective concentration range for a long time, the drug release is mainly released at a zero-order or close to zero-order rate within a predetermined time.
Slow and controlled release drugs are generally suitable for drugs with short half-lives, and their half-lives are generally between 2 and 8 hours. The drugs made into slow and controlled release preparations mainly include the following categories: antiarrhythmic drugs, antiangina, antihypertensive drugs, Antihistamines, bronchodilators, antiulcer drugs, antiasthma drugs, antipyretic analgesics, antipsychotics, iron salts, potassium salts, magnesium salts, etc. The antibacterial drugs are generally not suitable for controlled release preparations because their antibacterial effect depends on the peak concentration.
Compared with ordinary injections, the quality of special injections and the in vivo behavior of their active ingredients are more affected by the prescription and process, which may further affect the safety and effectiveness of the preparations in the body, such as liposomes, intravenous milk, Microspheres, suspension injections, etc., which are often referred to as complex injections. Special injections represented by microsphere preparations (liposomes, microspheres, emulsions, biological sustained-release injections, etc.) have produced many blockbuster products in the past decade. Nowadays, China’s pharmaceutical technology industry is in the process of rapid transformation, upgrading and development. As China’s new drug review has entered the ICH standard, the consistency evaluation of injections has begun. The development of new products for special injections and the consistency evaluation of marketed products have received unprecedented attention. The high-tech threshold is a rare opportunity and a huge challenge for powerful pharmaceutical companies in the fierce market competition.
Macromolecular preparations (drugs), also known as biological products, refer to microorganisms, cells, and various animals and humans that are obtained by ordinary or biotechnologies such as genetic engineering, cell engineering, protein engineering, and fermentation engineering. Medicines prepared from biological materials such as source tissues and liquids for the prevention, treatment and diagnosis of human diseases. Now the development of macromolecular drugs is getting faster and faster. At present, the annual sales of small molecule drugs are about 40 to 50 billion U.S. dollars, while biological drugs are only 10 billion. However, it is predicted that by 2020, the sales of small molecule drugs will reach 60 billion, and the sales of biological drugs will reach 30 billion. And by the middle of this century, around 2050, these two classifications will be the same, and there will be 60 billion. The above data also shows that the market share of macromolecular drugs will become higher and higher in the next few decades.
High-end generic drug preparations
From a macro perspective, cheap and high-quality generic drugs are the main contradiction of Chinese people’s current drug demand. One of the difficulties of generic drugs is to make a drug that can be replaced with the original research, but it cannot infringe many patent barriers set by the original research. There are too many difficulties and thresholds. Without innovation and technological accumulation, it is impossible to do well. Another difficulty is that it must be economical and must be developed and produced at a relatively low cost, otherwise it will lose its value.
Therefore, generic drugs need to balance science, risk control and cost: both technological innovation and institutional innovation are needed.