Application of new fast-dissolving technology in the research of orally disintegrating tablets

Orally disintegrating tablet refers to a tablet that does not require water or a small amount of water, and does not require chewing.
The tablet is placed on the tongue and dissolves or disintegrates quickly in saliva.
After swallowing, the drug can enter the stomach and take effect
.

The drug in this dosage form can be absorbed through the mucous membrane in the oral cavity or esophagus, with higher bioavailability than ordinary preparations, and the side effects caused by first-pass metabolism can also be reduced

In August 2003, the former State Food and Drug Administration (SFDA) named the quick-release tablets, oral quick-dissolving tablets, and orally disintegrating tablets uniformly as orally disintegrating tablets, and reviewed them as new preparations
.

At present, the preparation methods of orally disintegrating tablets include tableting method, sublimation method, molding method, phase change method, freeze-drying method, 3D printing and so on

Freeze drying technology

Freeze-drying technology is a drying method that removes the water in the drug solution by sublimation under low temperature conditions while retaining the active ingredients in a solid matrix
.

The preparation process is to mix gelatin, sucrose or other sugars, drugs and other ingredients (such as colorants) in a liquid or semi-solid state, and fill them into a molded board after foaming.

In the 1970s, the British Wyeth Company and Scherer Company prepared the first oral quick-dissolving tablet Zydis (ondansetron tablet) by freeze-drying, which can disintegrate in a small amount of water or on the tongue within 10 seconds
.

Since then, products such as Spasfon-Lyoc (Phloroglucinol oral freeze-dried tablets) have been born

Advantages of freeze-dried orally disintegrating tablets

①The disintegration speed is faster, and a stable skeleton structure has been formed during the pre-freezing process.
Therefore, the original structure of the skeleton remains basically unchanged after the water is removed by vacuum drying
.

The finished product is loose and porous like a sponge with obvious pores, so it can quickly disintegrate in the oral cavity and has good rehydration

②The amount of excipients is small, and there is no need to add a large amount of fillers and disintegrants.
The tablet is small and can be swallowed without water.
It is more suitable for patients who have difficulty swallowing or refuse to take medicine
.

③Good stability.
The freeze-drying method can quickly remove 95% to 99% of water, which is suitable for the preservation of active ingredients and the preparation of heat-sensitive drugs
.

④The mouthfeel is better.
Orally disintegrating tablets prepared by freeze-drying method use hydrophilic polymer materials as the matrix, which is not easy to produce gritty feeling, and an appropriate amount of flavoring agent is often added to the prescription to improve the bad odor
.

3D printing technology

3D printing is a rapid prototyping technology that is based on the principle of "printing layer by layer, layer by layer", based on computer-aided design, and controlled by a computer to directly prepare objects with special shapes or complex internal structures
.

The orally disintegrating tablets prepared by 3D printing are formed by powder accumulation and solidification without a compression process, so the tablets have high porosity, high internal surface area and fast disintegration

In August 2015, the FDA approved Levetiracetam instant tablets (trade name: Spritam) prepared by Aprecia Pharmaceuticals using 3D printing technology
.

This is the first and currently only drug produced using 3D printing technology to treat partial seizures, myoclonic seizures, and primary generalized seizures in adults or children

The advantages and significance of 3D printing technology

       Product design complexity: 3D printing can control the appearance shape, internal structure, material composition of each area and other factors through the selection of printing materials, model design and adjustment of process parameters, so as to better control the drug release cycle and release location And release rate, etc.
, create new opportunities for drug delivery systems
.

       Product personalization: The high flexibility of 3D printing technology can achieve dosage changes by modifying the tablet size or filling percentage.
The pharmacist can determine the most suitable dosage and dosage form for the patient according to the patient’s gender, age, ethnicity and other information.
Then, relevant preparations are prepared through 3D printing technology.
In terms of medicine for children, 3D printing technology can ensure that children at different growth stages can obtain accurate drug dosages, and can achieve individualized dosage administration of highly active drugs
.

       On-demand manufacturing: 3D printing is different from the traditional formulation process.
This technology can produce finished products and apply them in a short time
.

Use 3D printing technology to prepare compound preparations to prevent patients from missing medications

       Easy to expand production: 3DP technology has simple operation, fast speed, good process repeatability, and easy industrialization
.
The process parameters and system parameters in the preparation process are all saved by the computer, and when the industrial scale-up is carried out, mass production can be carried out according to the original saved data
.
This simplifies and speeds up the transformation process from drug development to production, while reducing batch-to-batch variation
.

       In recent years, instant drug delivery systems are gradually becoming the main direction of medical research at home and abroad, and one of the hotspots of pharmaceutics research
.
With the increase in clinical demand for instant drug delivery systems and the continuous improvement of drug safety and effectiveness requirements, the unique advantages of new instant technologies such as freeze-drying technology and 3D printing technology in formulation research have led to numerous studies Wide attention from personnel and pharmaceutical companies
.
These new technologies can avoid the traditional preparation of instant technology shortcomings to some extent, giving instant preparation of new features, provide new ideas and strategies for the development of new instant formulations
.

       references:

       [1]Ju Xiaoli, He Jun, Yang Yani, Bian Wei, Ni Meiping.
Application of new instant technology in the study of rapid release preparations[J].
Chinese Journal of Pharmaceuticals, 2017, 48(03): 434-441.

       [2] Wang Senyi, Li Sijia, Tu Yingying, Li Linghui, Jiang Shuguang.
Application and challenges of 3D printing technology in oral solid preparations[J].
Chinese Journal of New Drugs, 2020, 29(08): 881-889.

       [3]Shi Jing, Wang Zengming, Zheng Aiping.
Application and challenges of 3D printing technology in pharmaceutical preparations[J].
Progress in Pharmaceutical Sciences, 2019, 43(03): 164-173.
       

       About the author: Sha Luo, a Chinese medicine research and development worker, currently works for a large domestic drug research and development company, and is committed to the research and development of new Chinese medicines
.