Double-chamber prefilled needle lyophilized product

The following article is from Shixi , by Shengyi Shixi.
Picking sesame seeds and harvesting watermelon prefaces most lyophilized products on the market cannot simply be combined with standard syringes as they require a reconstitution step
before administration.

However, in the case of home care and emergency use, people still expect to reduce the number of procedures and the use of professional requirements
.

With this requirement, the dual-chamber system (DCS) offers an even better option that allows in-situ reconstitution and administration
.

Due to the high proportion of lyophilized dosage forms in approved biopharmaceutical products, DCS is expected to show an upward trend and has the potential to become a souxuan product
in the first aid and home care markets.

Until today, however, there are only a few products on the market due to the challenges and limitations of dual-chamber construction in terms of manufacturability, product formulation and product stability, as well as economic considerations
.

Double-chamber prefilled needle double-chamber prefill needle is an extension of conventional prefilled needle, which designs two chambers in the conventional prefilled needle, one chamber stores the lyophilized active ingredient, and the other chamber is filled with a matching dilution solution
.

This design has the advantage of being similar to the water prefill needle while retaining the advantage
that lyophilized formulations are easy to store.

When in use, push the mandrel piston and press the central rubber stopper through the bypass path on the cylinder wall with pressure, so that the diluted solvent flows through the "pathway" into the chamber where the lyophilized preparation is located, and then mixes for use
.

Application of lyophilization technology Vacuum freeze-drying, referred to as lyophilization, refers to the process
of drying solid materials directly into a gaseous state without passing through the liquid phase under vacuum conditions.

During the lyophilization process, the solvent is directly sublimated from the solid state to the gaseous state, so it does not destroy the original chemical structure and form of
the solute.

Biologically active materials can still restore pre-lyophilized conformational and biological functions
after re-dissolution.

Therefore, lyophilization is a safe drying method
that has little impact on the properties of the substance being dried.

Its production process, roughly as follows: For this production process, due to the special structure of the double-chamber prefilled needle, the contact surface between the bottle and the plate layer is very small, so that the lyophilized preparation in the lyophilization process, the energy required is more through convection and thermal radiation, rather than heat conduction, in different stages of the energy source is roughly as follows: prefreeze: convection > thermal radiation > conduction drying: thermal radiation > convection > Conduction also means that the lyophilization temperature of the product is controlled
by the temperature of the lyophilizer plate.

Of course, the double cavity pre-filled needle can be equipped with a sleeve or other set, so that the needle tube wall and the metal sleeve contact, thereby increasing the influence of heat conduction on the process, the entire process design should ensure the sterility
of the process.

In addition, there is a slightly different production process (the syringe cap is in contact with the lyophilizer plate): in this way, the cooling rate of the double-chamber prefilled needle is still slower than that of conventional vials, about 40%, and the final prefreeze temperature is 8.
2 degrees
Celsius higher than the plate.

Therefore, it is recommended to apply the concept of "design space" in research and development, amplification and transfer as much as possible to understand the impact of packaging material specifications (different suppliers), chemical solution (composition, filling volume) and process parameters on the final properties of
the product.

The production process of lyophilized products in the top chamber of the DCS double chamber system has two forms: 1.
"Needle upward needle-up" relative to the traditional form of production, based on the packaging material first need to be cleaned, sterilized, siliconized, and then through the glass syringe barrel opening end inserted into the middle plunger rubber stopper, DCS flipped over, so that its head is always facing up, the need to freeze-dried products through the DCS head into the corresponding chamber, obviously this requires a relatively large opening at the top of the glass container, and can not use a glass syringe
with a small diameter such as a Luer cone.

It is then placed in a support container, such as the positioning barrel Puck or the loading cassette Magzine (pictured below), and then transferred to the lyophilizer for lyophilization
.

After lyophilization, the top sealing cover is pressed through the plate layer to enter the next thinner filling process
.

2.
"Needle downward needle-down" This PFS production mode based on the current common RTU packaging material, in the whole production process, DCS does not need to be flipped, that is, after filling the lyophilized liquid of the drug, the glass syringe is directly placed in the special support container, and then enters the lyophilizer to complete the lyophilization process
.

Regardless of the above form of production process, it will use different forms of support containers, the design of the support container is not only to consider the stability of DCS transport, but also more importantly to increase the contact area of DCS glass cylinder and lyophilizer plate layer, so as to maximize the heat transfer efficiency
.

This is because regardless of the form, the contact area between the DCS glass cylinder and the plate layer is extremely limited, resulting in its lyophilization process being significantly different from the lyophilization
of vials.

In other words, the design and material selection of the support vessel is directly related
to the thermal conductivity efficiency of the DCS during the lyophilization process.

There are two common DCS on the market, pre-filled needle PFS and cartridge, the main difference between the two is the head closure design (head closure design).


The table below lists the 13 DCS products on the market, of which 5 are dual-chamber syringes and the other 8 are dual-chamber cartridges, but this does not represent any so-called trend
in the choice of syringes or cartridges.

ConclusionAt present, only a few enterprises on the market provide lyophilized products of dual-cavity systems, and due to the volume limitation of pre-filled needles or cartridges, most of the products are filled with a volume of 1ml to 5ml, but it is undeniable that this form of administration is convenient for home care and emergency medication, and there should still be a large potential market waiting to be tapped
.

In addition, the current production form will rely on the traditional lyophilization process, that is, rely on the lyophilizer loaded with the plate layer for production, so that the entire process is still too complicated
.

Beijing Songyuan Huaxing Technology Develop Co.
, Ltd.
was founded in 2000, focusing on the research and development, production and sales of vacuum freeze drying technology products, with "vacuum freeze dryer" as the core product, forming a scientific research experiment, medical, food industry, different scales, Three series of products and targeted solutions for different applications, is the domestic influential supplier
of vacuum freeze drying equipment and targeted solutions.

Beijing Songyuan Huaxing is a national high-tech enterprise, Beijing industrial enterprise safety production standardization enterprise, passed the ISO9001:2015 quality management system certification and EU CE certification
.

Headquartered in Beijing, it has branches and special maintenance stations
in Shanghai, Guangdong, Wuhan, Xi'an, Chengdu, Fuzhou, Nanjing and other places.

At the same time, Beijing Songyuan Huaxing is exported to the United States, Russia, South Korea, Japan, Singapore, Malaysia, Canada and other countries
with its products.

The image comes from the Internet and the copyright belongs to the original author
.