Research and development of new methods and technologies for the world transdermal drug delivery system
2019-09-09 16:04:37
According to different drugs, there are many ways to promote transdermal penetration, mainly: 1 transdermal absorption enhancer; 2 ultrasonic method; 3 iontophoresis method; 4 electroporation method.
Transdermal absorption enhancer and transdermal absorption
Any substance that can help the drug to spread through the stratum corneum and epidermis of the skin is a transdermal enhancer and an absorption enhancer, collectively referred to as an accelerator. It is one of the active ingredients of Zui in modern TTS research. The Kontturi study suggests that transdermal enhancers appear to promote drug penetration by opening new osmotic pathways, increasing lipid skeleton disorder and increasing skin non-uniformity. Early studies were mostly limited to organic solvents such as propylene glycol, dimethyl formate, dimethyl sulfoxide, etc., among which dimethyl sulfoxide is good. However, toxicity and skin irritation limit its clinical application. The transdermal enhancer currently developed and used is good with azone. It can be said that it is a typical representative of transdermal enhancers. Recent studies have suggested that oxyzide can promote strong penetration. Low effective concentration, stable nature and low toxicity. No side effects. It can be widely used in transdermal drug delivery systems.
It has been proved that the transdermal promotion effect of oxyzide on the drug only plays a good role in promoting the concentration of zui at the good concentration of zui. Some studies have suggested that the concentration of zoi sulphate in the sputum is 2% to 6%. Between, but varies from medicine to medicine. Pan Xuchu used the simple chamber method to measure the transdermal absorption of oxaprozin with different concentrations of scutellarin. The results showed that 0.5% to 3.0% of oxazide could promote Transdermal absorption of Sapuqin, which has a nitrogen-containing ketone effect of 0.5, Zui Jia, Guo Qingdong and other studies have shown that 1% to 3% of the azide ketone penetrates the opioid analgesic dihydroetorphine Has a strong promotion.
It is worth noting that the use of a transdermal absorption enhancer in combination with a coordinated drug can reduce the amount of accelerator used, reduce unnecessary side effects, and reduce the amount of main drug. According to Zhang Qi et al., the classic effective Fang Xiaoqinglong soup in the "Treatise on Febrile Diseases" was modified into a Qinglong patch by adding a transdermal enhancer. Four kinds of transdermal enhancers, such as azide propylene glycol, borneol and peppermint oil, were used separately and randomly. Two kinds of combined use were used to investigate the effect of promoting penetration. The results showed that the combination of azide and propylene glycol had a better penetration effect, and the transdermal speed of the drug was greater than that of different transdermal enhancers. Gao Yusheng et al. also showed that the use of multi-promoters is better than single use.
At present, it is one of the research directions to find new transdermal enhancers from traditional Chinese medicines. More research is on oleic acid, peppermint oil, eucalyptus oil, and borneol. Chen Sen et al. passed the in vitro test of nimodipine absorption patch. Several groups of different concentrations of oleic acid and nitroxanthin were screened as penetration enhancers, and the results showed that 10% oleic acid prescription permeability was good. Li Juan et al. used 2% eucalyptus oil as a transdermal absorbent to develop a new non-steroidal anti-inflammatory analgesic drug, fenoprofen calcium, into a hydrogel -type transdermal absorption system, which overcomes the common oral preparations. Gastrointestinal adverse reactions have achieved satisfactory results. Hanif et al. studied the use of geraniol as a transdermal enhancer for 5-FU, which showed that geranic acid is similar to lauric azone. It affects the diffusion process of the drug and increases the permeability coefficient of 5-FU, but the effect is weaker than that of laurel. ketone.
Iontophoresis and velocity absorption
Recent 20 years of research have shown that iontophoresis is a promising method to promote transdermal absorption of drugs, especially for drugs that are difficult to achieve with transdermal enhancers, such as macromolecular drugs such as peptide proteins and ionic drugs. . The method is to increase the passage of drug molecules through the skin into the body by applying an appropriate electric field to the skin. The mechanism mainly includes the mutual convection of ions in the electric field and the increase of skin permeability caused by current. There are many factors affecting the efficiency of drug iontophoresis, such as current mode, intensity and energization time, physical properties of the drug, concentration, molecular weight, ionic strength, skin factors, and iontophoresis factors.
The combination of transdermal enhancers and iontophoresis technology can effectively improve transdermal absorption of certain drugs, especially macromolecular peptides. Hao et al. examined the effects of several accelerators on the permeation of insulin monomer percutaneous ion. The results showed that the combination of azide and propylene glycol had a synergistic effect, and the synergistic effect of the two was better.
Ultrasound and transdermal absorption
Ultrasonic (phonophoresis or sonophoresis) refers to the process of entering the tissue through the skin under the action of ultrasonic waves.
The mechanism of ultrasonic promotion of skin administration may be: 1 local thermal effect of administration, resulting in increased drug permeability; 2 local radiation pressure applied to promote the penetration of the drug along the wave propagation direction; Microfluidic action, enough to cause convective transport of drugs through the skin, especially through the transport of hair follicles and sweat glands; 4 ultrasonic waves cavitation, resulting in disordered arrangement of the skin's stratum corneum lipid bilayer, promoting percutaneous penetration of drugs.
Compared with the iontophoresis method, the ultrasonic method can penetrate 5 cm below the skin, and the ion-guided method reaches a depth of no more than 1 cm. Ultrasound-promoting antibiotics, steroids, nicotinic acid esters, and insulin transdermal drug delivery systems have been reported. The amount of ultrasound-introduced dose is related to the frequency, intensity, and exposure time of the drug and is related to the molecular weight and exposure of the drug. It is related to the part of the skin.
Electroporation and transdermal absorption
Electroporation (EP) is a pulsed electric field that temporarily and inversely increases the permeability of cells and tissue membranes, thereby facilitating the migration of drug molecules. The modern EP-promoting theory is that the application of short electric pulses changes the orientation of lipid molecules and causes the molecules to be ordered, forming new pathways and increasing permeability. At the end of the pulsed electric field, the lipid molecules revert back to their original disordered orientation, thereby closing the channel. When clinical use of heparin anticoagulation and prevention of thromboembolism, oral bioavailability tends to zero, subcutaneous injection is used for small doses, and intravenous infusion can only be used for large doses (heparin has a short biological half-life and dose bias) There is a big risk of bleeding). Therefore, transdermal administration of controlled speed is an ideal method for Zui. Prausintz's experiments laid the foundation for the clinical application of heparin's EP delivery system. Zui's recent research, especially in the transdermal delivery of peptide drugs, has made great progress, so it is believed that EP technology has the potential to make transdermal drug delivery for drugs that cannot be used in traditional transdermal drug delivery systems. Choose a drug.
Other techniques and transdermal absorption
Michael et al. have strong lipophilicity and made liposomes for transdermal treatment using two drugs that are difficult to penetrate into the skin by iontophoresis. The results showed that the liposomes were highly lipophilic, and the drugs which were difficult to penetrate into the skin by other substrates still had a promoting effect. Other studies have shown that skin re-exposure to the laser, skin permeability will increase by more than 100 times, therefore, some researchers believe that laser can promote transdermal absorption of drugs is a better transdermal drug delivery of various therapeutic drugs. method.
In summary, transdermal drug delivery systems are a new class of drug delivery systems. As the research progresses, more new technologies and methods will be developed, and more and more transdermal drug delivery systems will be applied to the clinic.
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