Emulsion Development Services

BOC Sciences is a biopharmaceutical company focused on the development of pharmaceutical formulations. With a combination of cutting-edge technology, expert scientists and full-service products, we are well positioned to help our customers develop stable, effective and scalable emulsion to enhance the therapeutic benefits of active pharmaceutical ingredients (APIs).

What is emulsion?

With the development of clinical application requirements and drug delivery technology, lipid emulsion has become an excellent carrier for insoluble drug delivery, which can package drugs into the oil phase, improve the solubility and stability of drugs, reduce adverse drug reactions and improve curative effect. The research and development of medicated lipid emulsions is based on the wide application of nutritional lipid emulsions, low safety risk, and easy industrial large-scale production.

Formulation of emulsions

The prescription composition of drug-loaded lipid emulsions is basically the same as that of nutrient lipid emulsions, except for API. Oil-in-water emulsion is mainly formed by emulsification of APIs, oil phase, emulsifier, isotonic agent and water for injection.

API

Generally, the greater the fat solubility of the drug (logP>4), the more conducive to the preparation of lipid emulsions. Raw material research concerns API impurities such as related substances, genotoxic impurities, etc., others should meet the current review requirements.

Oil phase

The choice of oil phase has great influence on the quality of lipid emulsions. The oil phase as a drug carrier should have stable physical and chemical properties, and the drug contained in the oil phase needs to have a good solubility. The most commonly used in medicated lipid emulsions are soybean oil and medium chain triglycerides. Because oil is easy to oxidize to produce peroxides, further oxidation decomposition into aldehydes, ketones, acids, the content of these substances is expressed by the value of methoxyaniline. Therefore, special attention should be paid to the storage conditions of the oil phase, and low temperature nitrogen storage should be paid to avoid oil oxidation, which is conducive to improving the quality of the finished product.

Emulsifier

Emulsifier, as one of the important components of medicated lipid emulsion injection, needs to meet the safety, non-toxicity, non-pyrogen and other conditions. One of the most widely used emulsifiers is yolk lecithin, which has been approved by the FDA for intravenous use. The role and concerns of lecithin as a key excipient can be seen in the summary of the main points of pharmaceutical research and development of nutritional lipid emulsions.

Additives

In addition to drugs, oil phase and lecithin, there are also pH regulators, osmotic pressure regulators, metal ion chelators or bacteriostatic agents, interfacial film stabilizers, antioxidants and so on. The pH regulator usually uses sodium hydroxide, hydrochloric acid, citric acid, etc. Osmotic pressure regulator such as glycerin, sucrose; Metal ion chelating agents or bacteriostatic agents such as disodium edetate; Interfacial film stabilizers, such as oleic acid or sodium oleate, improve the stability of lipid emulsions by increasing the strength of the interfacial film, increasing the repulsive force between droplets, preventing droplets from gathering; Antioxidants and reducing agents such as sodium sulfite and vitamin E are commonly used.

Our comprehensive emulsion development services

Emulsion development process

The commonly used preparation process of medicated lipid emulsions mainly includes shear emulsification, high pressure homogenization and sterilization. At present, the most widely used is the high shear method and high pressure homogenization method, generally known as the two-step emulsification method, which is suitable for mass production. The process is to dissolve drugs and phospholipids in the oil phase, the osmotic pressure regulator and other additives in the water phase, the water phase and oil are connected by high shear to prepare colostrum, and then high pressure homogenization to obtain the final emulsion, which is filtered, filled and sterilized.

Oil phase preparation

Generally, the main drug and emulsifier are dissolved in the oil phase, because the dissolution requires a certain temperature and time, and the oil phase and emulsifier (such as lecithin) contain more linoleic acid, linolenic acid, amide and other components containing double bonds, which are sensitive to heat and easy to oxidation, so the thermal stability of the main drug and other components needs to be comprehensively considered when preparing the oil phase temperature. The whole preparation process needs to be carried out under the protection of nitrogen, otherwise it is very likely that the peroxide value and methoxyaniline value exceed the standard, and the emulsifier will decrease the emulsifying ability due to oxidation and cause instability of the emulsion.

Water phase preparation

Generally, the osmotic pressure regulator and metal ion chelator are dissolved in the water phase. Considering that the pH of the water phase may affect the pH of the final product and the stability of the drug, and when the water phase and oil are mixed to prepare colostrum, different pH will affect the ionization of the phospholipids in lecithin, and oleic acid may saponify to produce sodium oleate under alkaline conditions, which has a further auxiliary effect on emulsification. Therefore, an appropriate amount of pH regulator is first added to the water phase. The whole preparation process needs to be carried out under the protection of nitrogen to prevent the introduction of residual oxygen during the mixing of oil and water from affecting the quality of the product.

Colostrum preparation

The preparation of colostrum is the key link of fat emulsion. Since fats contain unsaturated fatty acids, fats and phospholipids are easy to be oxidized in the production, thus affecting the quality of finished products, and drugs may be easy to oxidize, etc. Therefore, the residual oxygen should be strictly controlled in the feeding, preparation of water phase, oil phase, emulsification and the whole preparation process. The key process parameters need to control the dissolved oxygen and the residual oxygen in the preparation system. When phospholipids are used as emulsifiers, the emulsification temperature is the key parameter, and it is more appropriate to control the emulsification temperature in the preparation of colostrum at 50-70 °C, and the thermal stability of the drug should be considered. During the preparation of colostrum, pH will affect the hydrolysis of drugs, the ionization of phospholipids in lecithin, oleic acid may also saponify to produce sodium oleate under alkaline conditions, which has an auxiliary effect on emulsification, so the emulsion pH can be properly adjusted during the preparation of colostrum. The size and distribution of colostrum particle size may affect its stability before homogenization and its effect during homogenization. Therefore, it is necessary to use particle size as an indicator to screen out shear parameters suitable for production scaling-up. In order to reduce the microbial load of the liquid before sterilization and the risk of introducing small foreign matter into the finished product in raw materials, production equipment and components, production environment, etc., microporous filter membrane or filter element can be used for pretreatment when preparing water phase, oil phase and colostrum.

High pressure homogenization

The homogenization process is a key step in the entire process that determines the quality of the final emulsion. After the preparation of colostrum, it is unstable and easy to aggregate, flocculate, merge, and equalize. Therefore, homogenizing emulsification under high pressure is required to further reduce the particle size of emulsions and make the particle size distribution more concentrated. At present, high-pressure homogenization method is the mainstream technology. The homogenization process is an important step that affects the particle size of droplets. Only appropriate homogenization parameters can ensure the good stability of the product. The main factors affecting the particle size and stability of the sample during high pressure homogenization include: homogenization pressure and homogenization frequency, which need to be investigated in detail. In the process parameters, the pressure of primary valve and secondary valve is defined, and the droplet size control of lipid emulsion intermediate is controlled.

Filtering

After homogenization, the refined emulsion is filtered to remove some insoluble particles and reduce the microbial load. For products that cannot be sterilized by wet heat, the sterilizing filter (0.2μm aperture) is directly used for sterilizing filtration, and it is necessary to pay attention to the material and aperture of the filter element.

Filling

The oxidation of lipids and phospholipids will destroy the emulsion system and reduce its stability, so the residual oxygen should be strictly controlled during the filling process. In general, the air in the bottle is quickly replaced by the alternating operation of pumping vacuum and filling nitrogen, and the nitrogen is fully filled before filling the liquid to ensure the residual oxygen in the top space of the bottle.

Sterilization

Sterilization is the final guarantee of the quality of the lipid emulsion preparation, and the sterilization conditions are selected according to the product characteristics and the solution product sterilization decision tree. For products that can be sterilized by wet heat, a rotary autoclave is generally used during sterilization instead of a traditional water bath sterilization pot, in order to make the emulsion uniformly heated during sterilization and reduce the demulsification caused by uneven heating. Here, it is necessary to pay attention to the influence of the speed of the sterilization pot on the stability of the emulsion. In addition, the sterilization pot also needs to have the characteristics of fast heating and fast cooling after the end of sterilization, usually the way of direct sterilization with hot water or steam, after the end of sterilization, cooling water is passed into the rapid cooling to reduce the production of free fatty acids, so the sterilization process should be optimized, and the over-killing method is preferred. In the process of research and development, it is also necessary to pay attention to the change of pH value before and after sterilization of fat emulsion, the degradation of related substances and the influence on the stability of the emulsion.

Quality control

Since emulsion is a thermodynamically unstable emulsion dispersion, drugs may affect the structure and properties of oil-water interface film after drug loading, resulting in changes in stability. The key quality attributes of the emulsion were investigated, usually including: character, pH value, average droplet size, zeta potential, free fatty acids, peroxide value, methoxyaniline value, lysophosphatidylcholine and lysophosphatidylethanolamine, loading, glycerol content, phosphorus content, viscosity, etc. At the same time, drug content, related substances, encapsulation rate, in vitro release, droplet morphology and other key characteristics were considered in the process of research and development.

Comprehensive stability testing

Emulsions are prone to unstable mechanisms such as coalescence, flocculation, emulsification, or phase separation. Our services include a comprehensive stability testing program to ensure that the emulsion remains stable over its intended shelf life. The robustness of the emulsion is assessed through accelerated stability testing under various temperature and humidity conditions. At the same time, necessary adjustments can be made to the formulation, emulsifier selection or process parameters to improve stability.

Advanced technology and equipment capability

High-pressure homogenization

At BOC Sciences, our high-pressure homogenizers are capable of processing emulsions at pressures up to 2,000 bar, ensuring that the resulting formulations exhibit optimal droplet size distribution, which enhances both the stability and bioavailability of the drug. This method is ideal for producing nanoemulsions, which are essential for improving the delivery of poorly soluble drugs. BOC Sciences also provides nanoemulsion formulation services .

Microfluidization

Microfluidization technology uses high shear forces to break down particles and droplets to nanometer scales, further enhancing the stability of emulsions. Microfluidization is particularly valuable for creating high-stability emulsions used in intravenous drug delivery and other sensitive pharmaceutical applications.

Precision shear mixers

These mixers allow us to rapidly disperse the oil phase into the water phase or vice versa, ensuring a consistent initial emulsion that is suitable for further processing. The high-speed, high-torque capability of these mixers ensures efficient emulsification even with highly viscous ingredients or complex formulations.

Sterile filtration systems

We maintain a full range of sterile filtration systems, including membrane filtration and depth filtration, to ensure that emulsions are free from contaminants and particles. Our filtration systems can handle emulsions with various viscosities and droplet sizes, and they are optimized to preserve the structural integrity of sensitive formulations while removing impurities. This is particularly important for parenteral emulsions, where sterility and particle size control are critical for patient safety.

Automated filling and packaging

These systems operate under inert environments, such as nitrogen flushing, to minimize oxygen exposure and prevent the oxidation of sensitive ingredients. Our automated systems ensure that each unit is filled with the exact amount of emulsion, and they are designed to meet strict regulatory requirements for good manufacturing practices (GMP).

In-line particle size monitoring

These systems allow us to continuously monitor droplet size distribution and adjust process parameters in real-time, preventing batch-to-batch variability.

Why choose BOC Sciences?

• Time and cost efficiency.
• Each emulsion formulation is uniquely designed to meet the specific needs of the client.
• All formulations are developed in compliance with the highest regulatory standards.
• Emulsion formulations are designed for scalability, from small clinical trial batches to full-scale commercial production.
• End-to-end support

FAQ

1. What types of emulsions are there?

There are two primary types of emulsions:

Oil-in-water (O/W) emulsion: Oil droplets are dispersed in a continuous water phase. This type is commonly used in injectable formulations.

Water-in-oil (W/O) emulsion: Water droplets are dispersed in a continuous oil phase. This type is less common but useful for certain topical and sustained-release applications.

2. How do you control oxidation in emulsion formulations?

Nitrogen purging: To displace oxygen in the product container and prevent oxidation during storage.

Antioxidants: The addition of antioxidants such as tocopherols or ascorbic acid can protect against oxidative degradation.

Temperature control: Keeping the formulation process under controlled temperatures can help avoid the oxidation of sensitive ingredients.

3. What is the role of emulsifying agents in emulsion formulations?

Emulsifying agents stabilize the interface between the oil and water phases, preventing droplets from coalescing or aggregating. Common emulsifiers include phospholipids (e.g., lecithin), polysorbates, and block copolymers. The choice of emulsifier is critical for maintaining long-term emulsion stability.

4. What quality control tests are performed for emulsion products?

Particle size analysis: To ensure consistent droplet size and distribution.

Zeta potential: To measure the surface charge, which affects emulsion stability.

pH testing: To ensure that the emulsion maintains a stable pH.

Viscosity: To confirm the emulsion has the desired flow characteristics.

Microbial testing: To ensure sterility, especially for parenteral emulsions.

Accelerated stability testing: To assess emulsion stability under different environmental conditions.