The Impact of Excipients on Bioavailability and Therapeutic Efficacy

In pharmaceutical development, excipients are often regarded as “inactive” components, yet their influence on bioavailability, stability, and even therapeutic efficacy is anything but passive. While traditionally used for manufacturing convenience and dosage form design, excipients today play a strategic role in optimising drug delivery outcomes.

This article explores how specific excipients impact pharmacokinetic profiles, absorption kinetics, and overall drug performance.

1. Solubility-Enhancing Excipients

For BCS Class II and IV drugs with limited aqueous solubility, excipients such as surfactants, co-solvents, and complexing agents can dramatically improve dissolution rates and absorption.

• Example: Sodium lauryl sulphate improves wetting and micellar solubilisation.
• Cyclodextrins enhance solubility through inclusion complex formation.
• PEG 400 and propylene glycol act as co-solvents to enhance solubilisation of lipophilic APIs.

2. Permeation Enhancers

Some excipients transiently increase the permeability of biological membranes, promoting paracellular or transcellular transport across the gastrointestinal epithelium.

• Example: Bile salts and fatty acids can alter membrane fluidity, enabling improved absorption.
• Chitosan has been shown to enhance mucosal adhesion and permeability, especially in nasal or buccal formulations.

3. pH Modifiers and Buffering Agents

Certain APIs exhibit pH-dependent solubility. Incorporating buffering agents into the formulation helps maintain an optimal microenvironment at the absorption site.

• Example: Citric acid or sodium bicarbonate may be added to maintain solubility and prevent degradation of acid- or base-labile drugs.

4. Inhibitors of Metabolic Enzymes and Efflux Transporters

Some excipients can modulate P-glycoprotein (P-gp) or CYP450 enzymes, reducing pre-systemic metabolism and improving systemic drug availability.

• Example: Cremophor EL and polysorbate 80 can inhibit P-gp-mediated efflux.
• Peppermint oil and grapefruit extract are known to interact with CYP enzymes, although use in formulation is highly controlled due to safety concerns.

5. Modified-Release Excipients

Hydrophilic matrices (e.g. HPMC) and osmotic agents can significantly alter the release profile of a drug, affecting Cmax, Tmax, and duration of action — all of which impact therapeutic efficacy.

• Example: Controlled-release systems may reduce peak–trough fluctuations, minimising side effects while maintaining plasma levels within the therapeutic window.

6. Stability and Compatibility Factors

Excipients influence both chemical and physical stability. Incompatible excipient–API combinations can lead to reduced potency, altered release, or unwanted degradation products.

• Example: Redox-sensitive APIs may degrade in presence of oxidising fillers, whereas antioxidants like BHT may stabilise sensitive compounds.

Conclusion

The selection of excipients is not merely a formulation formality — it’s a critical design decision that directly influences bioavailability and therapeutic performance. Understanding these interactions at the molecular and pharmacokinetic level enables smarter, more effective drug development.