Biopharmaceutical Excipients: Everything You Need to Know

Given the growing risk of infectious diseases, globally, pharmaceutical companies are shifting to biologics to treat patients. Biologics are compounds derived from different biological products, including blood, cells, genes, somatic cells, tissues, and other components. These biopharmaceutical drugs have been tailored to meet the patient's individual requirements. Despite its significance in treating diseases with exceptional efficacy and target specificity, these biologics are highly unstable and easily degrade when exposed to external environments. Biopharmaceutical excipients have emerged as a promising approach to provide extra stability to the drugs without altering their chemical properties.

Additionally, the biopharmaceutical excipient plays an essential role in carrying active components of drugs to the targeted sites. Ideally, these excipients are inert and do not possess any medicinal properties. However, these small active molecules play an integral role in drug absorption at the targeted sites in the patient's body. Further, the growing preferences of personalized therapies has also resulted in the requirement of excipients to enhance overall efficacy, stability, and target delivery of drugs. The following is detailed information about biopharmaceutical excipients, types, roles, and the evolving industry.

Biopharmaceutical excipients overview

In general, biopharmaceutical excipients are small active molecules that are included in therapeutic formulations, including monoclonal antibodies, vaccines, recombinant proteins, and gene therapies. Different types of pharmaceutical excipients have been developed to stabilize biologic products during manufacturing and storage.

Additionally, biopharmaceutical excipients play an essential role in biologics development—they enhance the bioavailability, solubility, and tonicity of APIs. Besides therapies, these excipients are also used as preservatives, antioxidants, and bulking agents. Biopharmaceutical excipients can increase product yield, stabilize the product, and reduce operational expenses. Owing to the increasing popularity of excipients in the healthcare and pharmaceutical industry, several industrial leaders have increased their research to explore their application beyond pharmaceutical drugs. The global biopharmaceutical excipients market size is estimated to grow from US$2.73 billion in 2024 to US$4.58 billion by 2035, representing a compound annual growth rate (CAGR) of 4.8% during the forecast period 2024–2035 (1).

Are biopharmaceutical excipients inert?

Biopharmaceutical excipients are passive bystanders—they do not react with final products; instead, they only stabilize them. Examples of the biopharmaceutical excipients include cellulose derivatives, polysaccharides, plant derivatives, and synthetic substances. Inorganic minerals and copolymers are widely used in biopharmaceutical products, as they are inert and improve the stability of the final drugs. In the healthcare industry, excipients are also used to add an extra layer to medical equipment and devices that are commonly used in surgeries (2).

Major examples of biopharmaceutical excipients

There is a wide range of biopharmaceutical excipients developed by key industrial leaders that are used for the production of therapeutic drugs. Some notable examples of biopharmaceutical excipients used as excipients or APIs are listed in Table I (3).

Functions of biopharmaceutical excipients

These excipients are primarily used to stabilize a therapeutic drug’s biopharmaceutical and physicochemical properties. However, some biopharmaceutical excipients are multifunctional, and they can be used for a variety of purposes. For instance, hypromellose (a cellulose derivative) is used as a medical device coating agent, suspending agent, viscosity-increasing agent, and emulsifying agent. Because biopharmaceutical excipients are an important part of medicinal formulation, researchers are required to test their ability to control the physicochemical properties that can influence the suitability of dosage forms prepared using excipients. According to the US National Formulary, the category of excipients and their functions are listed in Table II.

Trends in the biopharmaceutical excipients industry

Manufacturing and storage of biological modalities are exceptionally complex—these drugs require additives that help maintain their active ingredients, keeping them stable for longer. To meet the growing demand for novel biopharmaceutical excipients, several manufacturers are aiming to boost their production process to launch a wide range of excipients. The focus for developing advanced excipients will be improving solubility and stability of APIs. Going forward, the increasing requirement for generic drugs has surged the demand for excipients and co-processed excipients to coat on oral solid doses.

Additionally, advancing drug dosage technologies and requiring a cost-effective drug-releasing system are the key trends driving growth in this industry. Furthermore, the growth in the enteric-release drugs also supports the demand for versatile excipients that offer higher compatibility with different types of APIs.

Challenges in the manufacturing of biopharmaceutical excipients

It is worth noting here that the complex structure of biopharmaceutical excipients creates challenges in the production. One potential challenge that industrial leaders face while manufacturing biopharmaceutical excipients is complex guidelines. Furthermore, maintaining the purity and quality of biopharmaceutical excipients is essential to prevent adverse effects on the health of patients. The limited availability of raw materials required for the development of biopharmaceutical excipients can create challenges for manufacturers in supporting the ongoing demand for therapeutic drugs made with biopharmaceutical excipients. Additionally, complex manufacturing processes such as filtration, purification, isolation, and blending require advanced equipment (4).

Novel biopharmaceutical excipients addressing limitations

To date, there are limited excipients available specifically for managing the release of high-dose and controlled-release formulations. Thus, to address these concerns, several advanced biopharmaceutical excipients have been developed to ensure the controlled release of drug formulation (5,6).

Eastman BioSustane.This excipient overcomes the challenge such as poor solubility, depot formulation, extended release, and irrelevant deterrence. Eastman BioSustaneSAIB NF is a non-polymeric excipient isolated from bio-based material, namely sucrose. These are highly hydrophobic and offer multiple applications, such as:

• It can be a carrier for amorphous solid dispersion of poorly water-soluble therapeutic drugs.
• It serves as an abuse-deterrent biopharmaceutical excipient while formulating APIs that may cause side effects.
• It can act as a sustained-release excipient, which is highly compatible with poorly water soluble as well as water soluble therapeutic drugs.

Kollitab DC 87 L-BASF.Kollitab DC 87L acts as a filler, disintegrant, binder, and lubricant. It offers high flowability to provide superior tablet strength when applying compression forces. Kollitab also ensures quick tablet disintegration and acts as an all-in-one tableting solution to facilitate fast tablet development, reduce manufacturing complexity, and simplify the process of formulation.

EmulfreeDuo. Emulfree Duo is a ready-to-use Polyethylene glycol (PEG)-free system developed by GATTEFOSSE. This excipient has been developed to stabilize the oil phase inside the bi-gel by enabling homogeneous dispersion within the aqueous phase. With this biopharmaceutical excipient, the entire process can be done at room temperature. The ability to develop drugs at room temperature makes it ideal for sensitive drugs. Furthermore, this biopharmaceutical excipient is highly compatible with a broad range of solvents, oils, and penetration enhancers—making it optimal for the formulation of medicinal creams, lotions, and solutions.

EUDRACAP. EUDRACAP is a biopharmaceutical excipient developed by Evonik as a ready-to-fill coated capsule for quick drug release. This excipient is a pre-locked capsule that is the right fit for the drug filling manufactured in the form of powders, granules, and pellets. These pre-locked capsules are easy to close and open on standard capsule filling systems, making them an ideal choice for drug filling. Furthermore, this excipient also helps to protect APIs, which are sensitive to heat, gastric acids, moisture, and certain processing conditions. Several significances offered by this biopharmaceutical excipient are:

• optimal pH targeting
• optimizing absorption rates
• effective acid resistance for longer
• minimize clinical risk
• accelerate time to commercialize the drugs.

Apisolex. This is a solubility-enhancing excipient useful for injectable drug formulations. Apisolex provides a versatile approach for solving these poor solubility challenges and has played a significant role in formulating poorly soluble drugs into products with higher solubility, bioavailability, and drug effects.

Apinovex.This biopharmaceutical solubility-enhancing excipient has been formulated by Lubrizol Life Science for amorphous solid dispersions. It is a high-molecular-weight polyacrylic acid excipient designed to provide both formulation and processing benefits for spray-dried amorphous solid dispersions.

Parteck COAT.This is a polyvinyl-based excipient possessing a specialized structure specifically designed for fast-release film coating application. The optimal particle size of this excipient reduces drug dissolving times while preparing the therapeutic drug coating solutions. Moreover, the optimal size enhances the processing efficiency and provides extra stability against moisture and oxidation, making it suitable for film-forming polymers in drug coating. Several other benefits offered by the Parteck COAT are:

• quick preparation of drug coating liquids at room temperature
• improve surface finishing and enhance the overall formulation value
• low viscosity enhances efficiency and reduces process times at high polymer concentration
• stable oxygen and moisture barriers—efficient protection to moisture-sensitive active pharmaceutical ingredients.

Conclusion

Biopharmaceutical excipients play an important role in enhancing drug stability and bioavailability of biologics. Though biopharmaceutical excipients do not show any therapeutic activity, there are some excipients that show compatibility with drug substances. Despite the significance and functionality offered by these excipients in therapeutic drugs, there are several challenges that may hinder their widespread adoption. One of the potential challenges is the high cost associated with the discovery of excipients and development. To boost the production of excipients, several biopharmaceutical companies have taken collaboration initiatives with key players. It is interesting to highlight here that several biopharmaceutical excipient manufacturers are currently entering a strategic alliance to consolidate the challenges and enhance their manufacturing capability to meet the increasing demand for excipients in biologics. Further, the focus will remain on innovations that can address the concerns associated with the development of excipients. Driven by the increasing research activities in this field, the biopharmaceutical excipients market will grow substantially to deliver excipients targeting a wide range of therapeutic applications.

References

1. Roots Analysis. Biopharmaceutical Excipients Market. Rootsanalysis.com (accessed April 15, 2024).
2. Sage Journals. Are excipients inert? Journals.Sagepub.com (assessed April 9, 2024).
3. European Pharmaceutical. The Central Role of Excipients in Drug Formulation. Europeanpharmaceuticalreviews.com (assessed April 9, 2024)
4. Drug Development and Delivery. Advance Biologics Require Innovative Excipient Science. Drug-dev.com (assessed April 9, 2024).
5. European Pharmaceutical. Pharmaceutical Excipients Market to Witness Expansion. Europeanpharmaceuticalreviews.com. (assessed April 9 2024).
6. Outsourcing Pharma. Future Drugs Will Need Novel Excipients. Outsourcing-Pharma.com. (assessed April 9, 2024).