Quick Look: The Role of Functional Excipients

Functional pharmaceutical excipients play a crucial role in improving the bioavailability of oral solid dosage products. Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments, leading to low oral bioavailability. To overcome these challenges, excipients with specific functions are incorporated into the formulation to assist in the dissolution process of the drug or to improve the dissolution rate through various mechanisms.²

Excipients may endow pharmaceutical products with special functions such as controlled release and increased drug bioavailability.¹ For instance, the inclusion of a disintegrant in solid oral dosage forms usually promotes faster and/or more extensive dissolution compared to a formulation without it. Additionally, excipients can be used to produce dosage forms that reduce the number of doses by modifying the rate of drug release, thereby improving bioavailability.³

Excipients with multiple functions, such as alkalinizing agents, surfactants, and sugars, are used in formulations to increase the dissolution rate and improve drug solubility. These excipients can be co-processed to fulfill multiple roles, such as acting as a direct-compressible filler material that also functions as a binder and/or disintegrant.3 Furthermore, the addition of pharmaceutical excipients in drug formulations has been shown to alter the pharmacokinetics of APIs, resulting in improved bioavailability.⁴

Functional Excipient Examples

Microcrystalline Cellulose: This excipient is a widely used binder-diluent in tablets and capsules. It also serves as an adsorbent, anti-adherent, and disintegrant, contributing to the overall performance of the dosage form.⁶

Pharmaceutical Polymer Coatings: Coatings are used for controlled drug release, moisture control, and aesthetic purposes. They can be classified as conventional, functional (non-release modifying), or functional (release-modifying) coatings, each serving specific purposes to improve drug delivery.⁶

Sodium Chloride: This excipient is used as a tonicity-adjusting agent in oral solid dosage forms. It can also aid in improving drug solubility and dissolution rates.⁶

Polysorbate 80: This surfactant is commonly used to enhance the solubility of hydrophobic APIs in oral and parenteral suspensions. It is also utilized in the preparation of oil-in-water emulsions and as a solubilizing agent.⁶

Starch: Starch is a multifunctional excipient used as a tablet and capsule diluent, disintegrant, and binder. Despite the availability of newer excipients, starch remains one of the most commonly used tablet binders, disintegrants, and fillers.⁶

pH Adjusting Excipients: Substances such as calcium carbonate and di-sodium carbonate are used to adjust the pH of the local environment in controlled-release matrix tablets, thereby influencing drug release and bioavailability.⁷

Solid Dispersions: Excipients such as cyclodextrins and polymeric carriers are used to improve the solubility and dissolution rate of poorly soluble drugs through the formation of solid dispersions.⁷

Functional Excipient Advantages

Improved Drug Solubility: Functional excipients are specifically designed to enhance the solubility of poorly soluble drugs, thereby improving their bioavailability.⁸

Controlled Release: These excipients can provide controlled release of the active pharmaceutical ingredient, leading to optimized drug delivery and improved patient compliance.⁹

Multifunctionality: Functional excipients often serve multiple roles in the formulation, such as acting as a binder, disintegrant, and filler simultaneously, reducing the need for multiple excipients and simplifying the formulation process.³

Customization for Specific Drugs: They can be tailored to the specific needs of the drug being formulated, allowing for a more precise and effective drug delivery system.⁸

Enhanced Stability: Functional excipients can contribute to the stability of the drug product, ensuring that the active ingredient remains effective throughout its shelf life.¹⁰

Reduced Dosing Frequency: By improving drug bioavailability, these excipients can help reduce dosing frequency, leading to improved patient adherence and therapeutic outcomes.⁸

Potential Risks

Safety Concerns: While excipients are generally regarded as safe, there is a need for thorough safety evaluation, especially for new modifications or combinations of existing excipients. The International Pharmaceutical Excipient Council (IPEC) classifies excipients based on safety data into different categories, and updates on regulatory requirements for pharmaceutical excipients are continuously introduced worldwide to ensure their safety.¹²

Excipient Variability: Variability in excipients can affect drug product performance. Small changes in the raw material source can lead to significant changes in the drug product performance. Therefore, a lack of an adequate control strategy for excipient variability can pose a risk.¹³

Drug Product Recalls: Several drug product recalls have identified excipient variability as a contributing factor. Therefore, it is essential to have a robust control strategy for excipients to ensure consistent drug product performance.¹³

Potential Interactions: Excipients may interact with the active pharmaceutical ingredient or other components of the formulation, leading to unexpected effects on drug stability, release, or bioavailability.¹¹

Regulatory Compliance: The use of new or modified excipients may require additional regulatory scrutiny and compliance, which can impact the development and approval of oral solid dosage forms.¹²

Functional pharmaceutical excipients play a vital role in improving the bioavailability of oral solid dosage products by addressing poor drug solubility and low dissolution rates. By incorporating excipients with specific functions, pharmaceutical companies can enhance the dissolution process and ultimately improve the bioavailability of poorly soluble drugs.

In addition, functional pharmaceutical excipients offer a range of benefits over traditional excipients, including improved drug solubility, controlled release, multifunctionality, customization for specific drugs, enhanced stability, and reduced dosing frequency.

It is important for pharmaceutical companies to carefully assess the risks associated with the use of functional pharmaceutical excipients and to implement appropriate quality risk management strategies to ensure the safety, quality, and performance of oral solid dosage forms.

References

1. https://www.sciencedirect.com/science/article/abs/pii/ S0731708520316757
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284856/
3. https://www.pharmaexcipients.com/news/functional-excipients-solid-oral-dosage-forms/
4. https://www.researchgate.net/publication/341019895_The_Role_of_Functional_Excipients_in_Solid_Oral_Dosage_Forms_to_ Overcome_Poor_Drug_Dissolution_and_Bioavailability
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662502/
6. https://pharmacentral.com/products/25-most-popular-excipients-based-on-search-and-new-product-registration-data/
7. https://www.pharmaexcipients.com/news/functional-excipients-solid-oral-dosage-forms/ Citations
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284856/
9. https://www.sciencedirect.com/science/article/abs/pii/ S0731708520316757
10. https://pharmacentral.com/products/25-most-popular-excipients-based-on-search-and-new-product-registration-data/
11. https://www.sciencedirect.com/science/article/abs/pii/ S0731708520316757
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284856/
13. https://www.pharmtech.com/view/excipients-formulation-success

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