According to public data, the market size of topical preparations in the United States reached 10.2 billion US dollars in 2021, compared to 27.5 billion yuan in China during the same period. According to research data from ResearchandMarkets, the global transdermal patch market size was approximately $8.67 billion in 2019 and will increase to $10.67 billion by 2026.
From this, it can be seen that the market demand for topical preparations is broad and showing an increasing trend year by year. So, what are the advantages of topical preparations that have led to the market growth year by year?
From this, it can be seen that the market demand for topical preparations is broad and showing an increasing trend year by year. So, what are the advantages of topical preparations that have led to the market growth year by year?
Highlighting advantages, enterprises competing to layout
Skin topical drugs are a kind of preparations that act on the local or whole body through the skin, and their dosage forms mainly include plasters, patches, gel, etc. Compared to traditional oral medications, skin topical formulations have the following advantages:
(1) First of all, external drugs do not pass through the gastrointestinal tract, so compared with oral drugs, they can avoid the first pass effect effect of drugs in the gastrointestinal tract;
(2) External use of drugs on the skin can reduce the changes in blood drug concentration peaks and valleys, thereby reducing the side effects of drugs;
(3) Skin topical formulations can be directly applied to affected areas, reducing the frequency of administration;
(4) Patients with skin topical formulations have high compliance, and if adverse reactions occur during use, medication can be immediately interrupted.
Taking into account the above advantages, skin topical formulations can effectively improve patient compliance, such as ease of use, reduced frequency of medication, and reduced intensity of side effects. This is also the fundamental reason why patients are increasingly advocating skin topical formulations. Due to the favor of patients, many companies are also vying to expand into the field of skin topical formulations, bringing considerable profits to the company.
Taking Jiudian Pharmaceutical as an example, according to its 2022 annual report data, its exclusive variety loxoprofen sodium gel paste will have a revenue of more than 1.3 billion yuan in 2022.
On May 26, 2023, Henan Lingrui Pharmaceutical submitted an application for the listing of Mupirocin ointment. The cumulative sales of this variety in 2022 exceeded 700 million yuan, and its sales have been rapidly increasing in recent years. If approved for listing, it will also bring considerable profits to Henan Lingrui Pharmaceutical.
However, the layout of the field of skin topical preparations is not smooth sailing, and if one is not careful, it may lead to failure. Take flurbiprofen gel paste as an example, many enterprises have suffered from setbacks in their listing applications.
(1) First of all, external drugs do not pass through the gastrointestinal tract, so compared with oral drugs, they can avoid the first pass effect effect of drugs in the gastrointestinal tract;
(2) External use of drugs on the skin can reduce the changes in blood drug concentration peaks and valleys, thereby reducing the side effects of drugs;
(3) Skin topical formulations can be directly applied to affected areas, reducing the frequency of administration;
(4) Patients with skin topical formulations have high compliance, and if adverse reactions occur during use, medication can be immediately interrupted.
Taking into account the above advantages, skin topical formulations can effectively improve patient compliance, such as ease of use, reduced frequency of medication, and reduced intensity of side effects. This is also the fundamental reason why patients are increasingly advocating skin topical formulations. Due to the favor of patients, many companies are also vying to expand into the field of skin topical formulations, bringing considerable profits to the company.
Taking Jiudian Pharmaceutical as an example, according to its 2022 annual report data, its exclusive variety loxoprofen sodium gel paste will have a revenue of more than 1.3 billion yuan in 2022.
On May 26, 2023, Henan Lingrui Pharmaceutical submitted an application for the listing of Mupirocin ointment. The cumulative sales of this variety in 2022 exceeded 700 million yuan, and its sales have been rapidly increasing in recent years. If approved for listing, it will also bring considerable profits to Henan Lingrui Pharmaceutical.
However, the layout of the field of skin topical preparations is not smooth sailing, and if one is not careful, it may lead to failure. Take flurbiprofen gel paste as an example, many enterprises have suffered from setbacks in their listing applications.
The two sides of the 'coin' are the challenge of development difficulty
So what is the reason for the setbacks in product launch applications? The reason for this is still the difficulty in developing skin topical formulations, which leads to a certain gap in product quality compared to the reference formulations.
Complex and diverse prescriptions with high development barriers
According to public information, if topical skin preparations want to take effect, they generally need to go through the following processes:
◆ Successful drug release;
◆ The drug reaches the target of action;
◆ medication takes effect;
◆ The drug maintains a certain concentration in the body and exhibits stable therapeutic effects.
Simply mentioning the first two processes mentioned above, it involves how drugs are released into skin tissue and the need to control the release rate, which has frustrated many companies in this process.
In addition, the composition of skin topical formulations is complex and diverse, and the prescription can be composed of various components such as oil phase, water phase, surfactant, cosurfactant, and transdermal absorption enhancer. Changes in each component and process parameters may have an impact on the absorption and efficacy of the drug.
So from the perspective of composition, skin topical formulations are more complex than oral solid formulations and injections, and their thermodynamics is unstable. Their internal structure and performance will constantly change, and these subtle changes will have a significant impact on the clinical efficacy of drugs. The solution to this problem is simply to achieve consistency with the reference formulation as much as possible, which involves studying the quality of the formulation.
There are various key quality attributes, and the difficulty of research and development has skyrocketed
On March 16, 2021, CDE released the "Guiding Principles for the Research Technology of Skin Topical Chemical Genetics (Trial)". Although this guiding principle is specific to generic drugs, new drug research and development can also use this guiding principle to understand relevant quality research content.
(1) Prescription research
If it is a generic drug, it should refer to the reference formulation. Generally, the excipient type (Q1) and dosage (Q2) of the generic drug and the reference formulation should be basically the same. If it is a new drug, excipients can be selected according to actual needs. However, the following should be noted:
Pay attention to the influence of excipients on skin permeability, such as the effect of surfactants on the permeability of skin keratinocytes. At the same time, it is also necessary to consider the rationality and necessity of adding transdermal absorption enhancers, antibacterial agents, stabilizers, and antioxidants in the prescription. If it is indeed necessary to add them, corresponding information should be provided to ensure safety and effectiveness.
(2) Process research
For the process research section, as the production process has a significant impact on product quality, this guiding principle suggests referring to the relevant requirements of ICHQ8 and ICHQ9, and conducting sufficient research on the process steps and parameters that affect key quality attributes.
(3) Quality research
The key quality attributes of topical skin preparations generally include but are not limited to the following items: appearance, crystal form, particle size distribution, droplet size, rheological properties, pH value, viscosity, content uniformity, microbial limit, related substances, bacteriostatic agent content and antioxidant content Sterile preparations (used for burns (except for mild I ° or II °) or severe trauma), as well as in vitro release tests (IVRT) and in vitro transdermal tests (IVPT).
After solving the above problems, countless enterprises will eventually face the process of scaling up production, which has been a painful process. So what are the difficulties in scaling up the production of skin topical preparations?
Magnifying production parameters has a significant impact and high equipment requirements
Difficulty in process transfer: Skin topical formulations belong to complex formulations, and the first difficulty in scaling up complex formulations is that changes in process parameters have a significant impact on product quality. Before scaling up production, it is inevitable to undergo process transfer, and at this time, some parameter adjustments are usually made. However, due to the significant impact of changes in the process parameters of skin topical formulations on product quality, we should elaborate on the impact of each parameter on the product during the pilot phase and determine a parameter range as safe as possible.
High equipment requirements: Whether a device is good or not depends mainly on its accuracy. The fundamental reason is high accuracy, better product quality, and better inter batch parallelism. Due to the high requirements for parameter control accuracy in skin topical formulations, the control accuracy of equipment is also high. In the development process of skin topical formulations, equipment is a key link in determining the success of the drug.
So how to overcome the above difficulties? It goes without saying that in terms of equipment, it is natural to choose equipment with better performance. At the same time, it is best to match the pilot equipment with the small-scale equipment, which can reduce the difficulties encountered during the amplification process. As for the process, what we can do is to have a deep understanding of the projects we are working on, and it is very important to achieve the following three points:
During the project initiation stage, it is necessary to deeply analyze the prescription and process, establish key quality attributes, evaluate the properties of raw materials, excipients, and the impact of various process steps on product quality;
During the prescription and process development stage, we should conduct laboratory phase prescription and process inspections to confirm the impact of our prescription and process on product quality, and ultimately develop quality standards for raw materials and suitable process parameter ranges based on the impact;
Finally, we move on to the technology transfer stage, which involves changes in batch size and equipment. What we can do is to optimize the parameters of the pilot equipment by familiarizing ourselves with the equipment and the small trial parameters we have already determined, to ensure that the quality of the products produced in the scaled up production is not affected. In this process, the importance of the range of process parameters explored during the pilot phase is self-evident, but at the same time, the producer's understanding of the pilot and pilot equipment is also particularly important. The understanding of the equipment is a ruler in the heart when adjusting parameters.
Brief summary
Complex and diverse prescriptions with high development barriers
According to public information, if topical skin preparations want to take effect, they generally need to go through the following processes:
◆ Successful drug release;
◆ The drug reaches the target of action;
◆ medication takes effect;
◆ The drug maintains a certain concentration in the body and exhibits stable therapeutic effects.
Simply mentioning the first two processes mentioned above, it involves how drugs are released into skin tissue and the need to control the release rate, which has frustrated many companies in this process.
In addition, the composition of skin topical formulations is complex and diverse, and the prescription can be composed of various components such as oil phase, water phase, surfactant, cosurfactant, and transdermal absorption enhancer. Changes in each component and process parameters may have an impact on the absorption and efficacy of the drug.
So from the perspective of composition, skin topical formulations are more complex than oral solid formulations and injections, and their thermodynamics is unstable. Their internal structure and performance will constantly change, and these subtle changes will have a significant impact on the clinical efficacy of drugs. The solution to this problem is simply to achieve consistency with the reference formulation as much as possible, which involves studying the quality of the formulation.
There are various key quality attributes, and the difficulty of research and development has skyrocketed
On March 16, 2021, CDE released the "Guiding Principles for the Research Technology of Skin Topical Chemical Genetics (Trial)". Although this guiding principle is specific to generic drugs, new drug research and development can also use this guiding principle to understand relevant quality research content.
(1) Prescription research
If it is a generic drug, it should refer to the reference formulation. Generally, the excipient type (Q1) and dosage (Q2) of the generic drug and the reference formulation should be basically the same. If it is a new drug, excipients can be selected according to actual needs. However, the following should be noted:
Pay attention to the influence of excipients on skin permeability, such as the effect of surfactants on the permeability of skin keratinocytes. At the same time, it is also necessary to consider the rationality and necessity of adding transdermal absorption enhancers, antibacterial agents, stabilizers, and antioxidants in the prescription. If it is indeed necessary to add them, corresponding information should be provided to ensure safety and effectiveness.
(2) Process research
For the process research section, as the production process has a significant impact on product quality, this guiding principle suggests referring to the relevant requirements of ICHQ8 and ICHQ9, and conducting sufficient research on the process steps and parameters that affect key quality attributes.
(3) Quality research
The key quality attributes of topical skin preparations generally include but are not limited to the following items: appearance, crystal form, particle size distribution, droplet size, rheological properties, pH value, viscosity, content uniformity, microbial limit, related substances, bacteriostatic agent content and antioxidant content Sterile preparations (used for burns (except for mild I ° or II °) or severe trauma), as well as in vitro release tests (IVRT) and in vitro transdermal tests (IVPT).
After solving the above problems, countless enterprises will eventually face the process of scaling up production, which has been a painful process. So what are the difficulties in scaling up the production of skin topical preparations?
Magnifying production parameters has a significant impact and high equipment requirements
Difficulty in process transfer: Skin topical formulations belong to complex formulations, and the first difficulty in scaling up complex formulations is that changes in process parameters have a significant impact on product quality. Before scaling up production, it is inevitable to undergo process transfer, and at this time, some parameter adjustments are usually made. However, due to the significant impact of changes in the process parameters of skin topical formulations on product quality, we should elaborate on the impact of each parameter on the product during the pilot phase and determine a parameter range as safe as possible.
High equipment requirements: Whether a device is good or not depends mainly on its accuracy. The fundamental reason is high accuracy, better product quality, and better inter batch parallelism. Due to the high requirements for parameter control accuracy in skin topical formulations, the control accuracy of equipment is also high. In the development process of skin topical formulations, equipment is a key link in determining the success of the drug.
So how to overcome the above difficulties? It goes without saying that in terms of equipment, it is natural to choose equipment with better performance. At the same time, it is best to match the pilot equipment with the small-scale equipment, which can reduce the difficulties encountered during the amplification process. As for the process, what we can do is to have a deep understanding of the projects we are working on, and it is very important to achieve the following three points:
During the project initiation stage, it is necessary to deeply analyze the prescription and process, establish key quality attributes, evaluate the properties of raw materials, excipients, and the impact of various process steps on product quality;
During the prescription and process development stage, we should conduct laboratory phase prescription and process inspections to confirm the impact of our prescription and process on product quality, and ultimately develop quality standards for raw materials and suitable process parameter ranges based on the impact;
Finally, we move on to the technology transfer stage, which involves changes in batch size and equipment. What we can do is to optimize the parameters of the pilot equipment by familiarizing ourselves with the equipment and the small trial parameters we have already determined, to ensure that the quality of the products produced in the scaled up production is not affected. In this process, the importance of the range of process parameters explored during the pilot phase is self-evident, but at the same time, the producer's understanding of the pilot and pilot equipment is also particularly important. The understanding of the equipment is a ruler in the heart when adjusting parameters.
Brief summary
Due to its many advantages and vast market, topical formulations have gradually become a field that various enterprises are competing to layout. However, there are still some difficulties in the research and development of topical formulations and process transfer, which are also difficulties that each incoming enterprise needs to overcome. However, even though there are various pain points and difficulties in development, driven by market demand, with continuous technological innovation, the "bottleneck" technology for innovative research and development of topical formulations will eventually be overcome.
