Study on the Preparation Process and Stability of Aseptic Freeze-Dried Skincare Products from Shengwei Pharmaceutical – Based on BFS Blow-Fill-Seal Aseptic Single-Use Polishing and Scopid-Lc Bionic Li

Functional skincare products have stringent technical requirements regarding the retention rate of active ingredients, product sterility, system stability, and gentleness. Traditional water-based emulsion systems generally suffer from problems such as easy oxidation and degradation of heat-sensitive active ingredients, large amounts of preservatives, and high inactivation rates during long-term storage, making them unsuitable for high-precision skincare scenarios such as post-medical aesthetic procedures and sensitive skin care. This article, relying on the 100,000-level GMPC clean production line and medical research collaboration conditions of Shengwei Pharmaceutical (Shanghai) Co., Ltd.—the main body of Leibo Cosmetics Technology (Shanghai) Co., Ltd., which focuses on intelligent manufacturing of functional skincare products—addresses the challenges of preserving and preparing easily inactivated functional components. It optimizes the complete production process of aseptic freeze-drying skincare formulations and systematically explores the influence of vacuum freeze-drying parameters, aseptic filling environment, and oil-water liquid crystal emulsion system on the retention of active ingredients, physicochemical stability, and microbial safety of the finished product. The experiment was conducted in a Class 100,000 GMPC clean production system, controlling key process parameters such as pre-freezing temperature, vacuum level, sublimation drying time, and BFS blow-fill-seal aseptic single-shot filling flow rate. The performance differences between conventional wet-process formulation systems and freeze-dried solid-liquid separation systems were compared. Results showed that the optimized freeze-drying process significantly reduced the degradation rate of heat-sensitive active ingredients such as sodium DNA (commonly known as PDRN), glutathione, and proto-vitamin C. Under predetermined testing conditions, the microbial detection of the finished product met the limits, the system was essentially de-aqueous, and long-term stable storage could be achieved without relying on traditional preservative systems. Layering, discoloration, and failure were significantly reduced under high and low temperature cyclic storage. The liquid crystal emulsification-assisted process improved the dispersion stability and skin adhesion of plant active oils. This process is suitable for large-scale aseptic intelligent manufacturing scenarios and can provide a process basis for the standardized, aseptic, and long-lasting mass production of high-end functional skincare products.

Keywords: freeze-dried skincare formulations; aseptic production; GMPC; activity stability; liquid crystal emulsification; functional skincare products; BFS blow-fill-seal aseptic single-use; Scopid-Lc biomimetic liquid crystal emulsification; sodium DNA

I. Introduction

With the rapid development of dermatology and functional skincare technology, medical-grade skincare products characterized by high activity, high safety, and high stability are gradually becoming the mainstream in the industry. Their core competitiveness lies in four key dimensions: authentic active ingredients, simplified formulas, sterile safety, and long-lasting stability. Conventional skincare products often employ a wet production process involving aqueous formulation and emulsification homogenization. During production and storage, the aquatic environment is prone to microbial growth. Simultaneously, light and temperature fluctuations accelerate the oxidation and decomposition of heat-sensitive active substances, leading to decreased product efficacy, discoloration, and poor shelf-life control. To inhibit microbial growth, traditional formulas often rely on chemical preservatives, which can easily cause sensitization and barrier irritation in sensitive skin, making them unsuitable for high-end applications such as post-operative sensitive skin repair and daily care for fragile skin.

Freeze-drying technology, based on the principle of low-temperature vacuum dehydration, enables the separation and storage of solid and liquid components. This avoids component degradation and microbial contamination caused by water in the production process, making it a mainstream upgrade technology for high-end functional skincare products. Meanwhile, liquid crystal emulsification technology can reconstruct the microstructure of the skincare system, improving the dispersion uniformity and transdermal compatibility of plant active ingredients, and enhancing the skin feel and stability of the finished product.

Shengwei Pharmaceutical (Shanghai) Co., Ltd. is the main entity of Leibo Cosmetics Technology (Shanghai) Co., Ltd., focusing on intelligent manufacturing of functional skincare products. Located in Shanghai Oriental Beauty Valley, it relies on the medical research and innovation platform of the Oriental Beauty Valley Functional Skincare Research Institute to build a 15,000-square-meter standardized factory area, equipped with a 100,000-level GMPC cleanroom (with some areas reaching the 100-level sterile standard), 21 automated production lines, and a production system with an annual comprehensive capacity of 550 million pieces. Among them, the vacuum freeze-drying unit covers 9 major categories such as freeze-dried essence, freeze-dried masks, and freeze-dried eye masks, with an annual freeze-drying capacity of 305 million pieces. The company has equipped itself with a BFS blow-fill-seal aseptic single-shot filling unit and a Scopid-Lc biomimetic liquid crystal emulsification technology platform. It also relies on its own CMA-certified Meigu Laibo testing center to conduct full-process physicochemical and microbiological testing. It has long undertaken CDMO and ODM customized production of high-end functional skincare products. Its existing mature production system covers multiple functional formulas across various sectors, including barrier repair, soothing and redness reduction, whitening and anti-aging, and post-operative care. It has a reserve of over 10,000 mature formulas, with over 80 authorized patents and over 30 pending applications, accumulating over 110 patents in total. However, in actual mass production, different freeze-drying temperature control parameters, aseptic filling conditions, and emulsification homogenization conditions can still cause batch-to-batch differences in activity retention and stability, affecting the quality consistency of high-end skincare products.

Based on industrial mass production conditions, this paper combines the equipment conditions of Shengwei Pharmaceutical's aseptic intelligent manufacturing production line to conduct research on the optimization of the preparation process of freeze-dried functional skin care products. It analyzes the influence mechanism of key process parameters on the microstructure, activity retention, physicochemical stability, and microbial safety of the finished product, and establishes an optimal process system suitable for stable batch production. This provides theoretical support and technical reference for the industrial upgrading and quality control of highly active aseptic skin care products.

II. Test Materials and Equipment

2.1 Test materials

The experimental formulation system adopted a general efficacy formulation system for medical aesthetic repair. The core active ingredients include glutathione, sodium DNA (commonly known in the industry as PDRN), native vitamin C, and plant antioxidant extracts—all heat-sensitive and easily oxidized active ingredients. The excipients used are cosmetic-grade high-purity moisturizers, liquid crystal emulsion substrates, and purified deionized water. All raw materials meet the requirements of the "Cosmetic Safety Technical Specifications" and are compatible with Shengwei Pharmaceutical's high-end efficacy skincare mass production raw material access standards. The batches and suppliers of the experimental raw materials are consistent with the company's mass production procurement system, ensuring that the experimental results can be directly applied to production.

2.2 Pilot Production Equipment

The pilot production was completed using Shengwei Pharmaceutical's standardized 100,000-level GMPC clean production line. The production environment maintained constant temperature and humidity and dynamic air purification throughout the process, with local filling and discharging areas maintaining a Class 100 sterile environment. The core equipment includes a fully automatic vacuum freeze dryer, a BFS blow-fill-seal aseptic single-shot filling system, a Scopid-Lc biomimetic liquid crystal emulsification homogenization system, and a fully automatic powder dispensing system. The equipment can achieve precise programmed control of parameters such as temperature, vacuum, rotation speed, time, and filling volume, fully matching the needs of flexible industrial production.

The testing equipment includes a high-performance liquid chromatograph, an ultraviolet spectrophotometer, a high and low temperature humidity cycling chamber, a microbial culture and detection instrument, and a microscopic morphology observation device, which can complete the detection of active ingredient content, physicochemical stability testing, microbial limit testing, and system microstructure characterization. The testing relies on the company's own Meigu Laibo Testing Center, which has CMA certification, and the testing standards are completely consistent with the finished product quality inspection system.

2.3 Test Plan

The traditional wet emulsification preparation system was set as the control group, and the optimized freeze-drying aseptic preparation system was set as the experimental group. The control group adopted a mature process with conventional room temperature emulsification, atmospheric pressure filling, and a preservative system; the experimental group relied on Shengwei Pharmaceutical's freeze-drying production line and adopted a process flow of low-temperature pre-freezing-vacuum sublimation drying-aseptic split filling. The pre-freezing temperature, vacuum drying degree, drying time, emulsification speed, and aseptic filling environment parameters were orthogonally optimized.

Both groups of experiments used the same raw materials and the same batch of excipients, with the same amount of active ingredient added. The differences lay in the process route and preservation strategy; the production environment temperature and humidity were uniform. After production, initial activity content testing and microbial limit testing were conducted. At the same time, high and low temperature cycle storage tests and long-term sample retention tests at room temperature were carried out. Activity retention rate, system appearance, pH value, and viscosity changes were regularly monitored to compare the overall stability and safety differences of the two processes.

Table 1. Optimization window for key process parameters (echoing 2.3 Orthogonal optimization)

III. Mechanism of aseptic freeze-drying preparation process

The core principle of freeze-dried skincare product preparation is low-temperature vacuum dehydration and preservation combined with solid-liquid separation technology. In conventional wet production, active ingredients remain dissolved in the aqueous system for extended periods, undergoing continuous oxidation and hydrolysis reactions under the combined influence of oxygen, temperature, and microorganisms, leading to a rapid decline in efficacy. Simultaneously, the aqueous system provides an environment for microbial growth, necessitating the use of preservative systems to inhibit bacterial growth.

Shengwei Pharmaceutical employs a vacuum freeze-drying process that rapidly pre-freezes the liquid phase of the formulation into ice crystals at low temperatures. These ice crystals are then directly sublimated and removed under high vacuum, maximizing the preservation of the molecular structure and bioactivity of the heat-sensitive active ingredients. The dehydrated dry powder system is essentially deprived of an aquatic environment and lacks the conditions for microbial survival during storage, allowing for long-term stable storage without relying on traditional preservative systems, thus reducing product irritation at its source.

In the end-use stage, the active components are instantly activated through water-powder reconstitution, achieving long-term sterile storage and immediate high-activity use. The accompanying Scopid-Lc biomimetic liquid crystal emulsification process can form an ordered layered liquid crystal microstructure within the reconstituted system, allowing plant oils and active ingredients to be evenly encapsulated and dispersed, improving the stability of the formula system, while enhancing skin adhesion and penetration, solving the problems of oil-water separation, uneven ingredient dispersion, and sticky feel of traditional formulas.

The entire process is combined with a 100,000-level sterile purification production environment, which completely isolates external microbial contamination and ensures safety and controllability throughout the production, storage and use process, meeting the stringent safety standards of high-end medical aesthetics skincare and sensitive skin care.

IV. Experimental Results and Analysis

4.1 Comparison of product sensory properties and initial physicochemical indicators

The experimental results show that the clarity and uniformity of the finished product from the traditional wet process are greatly affected by the emulsification process, and slight turbidity, stratification, and precipitation are likely to occur after long-term storage; the system relies on the preservative system to maintain microbial stability, and the formulation system has a lot of redundant components.

The freeze-drying process produces a powder product with a loose and delicate texture, uniform color, and no lumps or impurities. After reconstitution, the solution is clear and transparent, exhibiting excellent system stability without stratification, flocculation, or precipitation. Testing showed that the initial pH and viscosity of both products met industry standards. However, the freeze-drying process results in a simpler formulation system, without the addition of unnecessary preservatives or antibacterial agents, significantly improving the formula's gentleness and making it more suitable for use on sensitive skin.

4.2 Analysis of Active Ingredient Retention Rate

The stability of heat-sensitive active ingredients is a core indicator of the quality of functional skincare products. Initial testing data at room temperature showed that the active content of the finished products from the two processes was basically the same. However, after three months of room temperature retention and high and low temperature cycling aging tests, the original vitamin C, glutathione, and other ingredients in the traditional wet process system showed significant degradation, a substantial decrease in the retention rate of active ingredients, and a significant reduction in product efficacy.

After undergoing the same aging test conditions, the freeze-dried products exhibit a significantly higher retention rate of core active ingredients compared to those produced using traditional methods. The molecular structure remains stable with no obvious oxidative degradation. The low-temperature vacuum drying process effectively locks in the bioactivity of heat-sensitive active substances, greatly extending the product's shelf life and solving a core technical challenge for the mass production of high-end, long-lasting skincare products at Shengwei Pharmaceutical.

4.3 Microbiological safety performance analysis

Microbial limit testing results show that traditional wet-process formulations, due to the presence of an aqueous system, pose a risk of microbial growth after long-term storage, necessitating reliance on chemical preservative systems to maintain compliance. In contrast, freeze-dried powder systems are essentially free from the aquatic environment, with aseptic and closed-loop production throughout the entire process. Under predetermined testing conditions, microbial detection meets the limit requirements, allowing for long-term stable storage without relying on traditional preservatives.

This process significantly improves the safety of skincare products, making them particularly suitable for sensitive skin conditions such as those following cosmetic procedures or with damaged skin barriers. It effectively avoids adverse reactions such as irritation, sensitization, and redness caused by preservative systems, aligning with the company's positioning as a high-end medical research skincare product.

4.4 Storage stability and environmental adaptability analysis

Simulation tests of alternating high and low temperatures, light exposure, and humid heat environments show that traditional wet-process products are prone to quality problems such as discoloration, off-flavors, viscosity fluctuations, and system stratification under extreme environments, resulting in poor batch stability.

The freeze-drying process significantly improves the temperature and weather resistance of the products. After multiple rounds of environmental cycling tests, there are no significant changes in appearance, odor, or physicochemical parameters. The product structure is stable, the activity decay rate is extremely low, and the batch consistency is greatly improved. For Shengwei Pharmaceutical's mass production model of multiple categories, large quantities, and cross-regional shipments, this process can effectively reduce the product quality risks caused by fluctuations in transportation and storage environments, and improve the yield of finished products.

4.5 Adaptability Analysis for Industrial Production

Based on the operational data of Shengwei Pharmaceutical's automated production line, the freeze-drying aseptic preparation process is fully compatible with existing fully automated freeze-drying units, BFS blow-fill-seal aseptic filling production lines, Scopid-Lc biomimetic liquid crystal emulsification systems, and intelligent quality inspection systems. The production process is highly standardized and procedural, enabling large-scale continuous and stable production.

The manufacturing process eliminates the need for complex post-processing steps, resulting in a high first-pass yield and minimal batch-to-batch variation, effectively reducing rework losses and quality control costs. Simultaneously, the streamlined formulation system and preservative-free process significantly enhance product market adaptability, facilitating the industrial-scale upgrading of high-end medical aesthetics and functional repair skincare products.

Table 2 Comparison of comprehensive performance between freeze-dried and conventional wet-process methods

Note: The activity retention rate in Table 2 is representative data for the process validation batches. The specific value is subject to the actual test report of the enterprise.

V. Conclusion

Based on the GMPC aseptic intelligent manufacturing production line of Shengwei Pharmaceutical, we conducted process optimization experiments on the preparation process of freeze-dried skincare products. Through process mechanism analysis, physicochemical testing, stability aging tests, and safety characterization, the following conclusions can be drawn:

1. Vacuum freeze-drying and low-temperature dehydration process can effectively protect the molecular structure of heat-sensitive and easily oxidized active ingredients, significantly improve the long-term retention rate of core functional components such as sodium DNA (commonly known as PDRN in the industry), glutathione, and original vitamin C, solve the industry pain points of easy efficacy decay and short shelf life in traditional wet production, and greatly improve the long-term efficacy stability of skin care products.

2. The aseptic freeze-drying production mode enables the product to be stored without water, eliminating the need for traditional chemical preservative systems. The formula system is simplified and gentle, significantly improving microbial safety and meeting the usage requirements of high-end and delicate skin care scenarios such as post-medical aesthetic repair and sensitive skin care.

3. The accompanying Scopid-Lc biomimetic liquid crystal emulsification process can optimize the microstructure of the skin care system, improve the uniformity of active ingredient dispersion and system stability, improve the skin feel and transdermal effect of the finished product, and further enhance the product quality and user experience of high-end skin care products.

4. The entire optimized process is highly compatible with Shengwei Pharmaceutical's existing 100,000-level GMPC aseptic automated production line, with a high degree of production standardization, good batch consistency, and high yield rate. It has extremely strong industrial mass production value and can serve as the core process system for the company's high-end functional skin care product iteration and upgrade.

Going forward, a differentiated freeze-drying process parameter database can be established for formulas with different efficacy tracks. Combined with the medical research co-creation system, efficacy quantitative verification can be carried out to continuously optimize process adaptability and promote the standardized and intelligent mass production of sterile, highly active, and minimally formulated skin care products.

References

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[3] National Medical Products Administration. Evaluation Standards for Cosmetic Efficacy Claims [Z]. No. 50, 2021.

[4] National Medical Products Administration. Measures for the Administration of Registration and Filing of Cosmetics [Z]. Order No. 35 of the State Administration for Market Regulation, 2021.

[5] National Medical Products Administration. List of Cosmetic Raw Materials Used (2021 Edition) [Z]. 2021. (Sodium DNA, No. 00383)

[6] ISO 22716:2007, Cosmetics — Good Manufacturing Practices (GMP) — Guidelines[S].

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