How to Improve APIs Bioavailability in Solid Oral Formulations?

In the pharmaceutical industry, ensuring the bioavailability of active ingredients is crucial for the effectiveness of orally administered treatments. Bioavailability refers to the proportion of a drug that successfully reaches systemic circulation and its intended therapeutic site after administration. Among various factors influencing bioavailability, solubility plays a critical role. The solubility of active ingredients directly affects pharmacokinetic parameters such as absorption, distribution, and protein binding, which can impact drug development success rates.

According to the Biopharmaceutics Classification System (BCS), Class II and IV molecules exhibit low solubility and dissolution rates, which result in lower bioavailability. Despite this, approximately 40% of marketed drugs have poor aqueous solubility, and nearly 90% of new chemical entities (NCEs) in development belong to BCS Class II or IV. These molecules are promising therapeutic candidates, but their poor solubility restricts absorption in the gastrointestinal tract, ultimately limiting their therapeutic potential.

Oral formulations present a particularly significant challenge, as they account for nearly half of all pharmaceutical forms administered. To address this issue, extensive research has been conducted to enhance drug formulations using functional excipients. These excipients play a vital role in improving solubility and bioavailability, allowing existing drugs to be reformulated for better therapeutic outcomes and increased cost-effectiveness.

One such innovative solution is SEPITRAP™, designed to overcome the limitations of poorly soluble active ingredients. Its unique properties enhance solubility and dissolution, optimizing bioavailability and improving the performance of oral formulations. SEPITRAP™ offers pharmaceutical experts a solution that aligns with therapeutic efficacy, economic viability, and patient convenience.

What is SEPITRAP™?

SEPITRAP™ is a powdered solubilizer developed to facilitate the production of solid oral medications. This innovative solution, created by Seppic, acts as a surfactant in powder form, simplifying the direct compression manufacturing process while simultaneously enhancing the solubility of poorly soluble APIs. The patented technology involves adsorbing a liquid solubilizer onto a porous carrier, Magnesium Aluminometasilicate.

SEPITRAP™ consists of a carefully engineered combination of surfactants and porous carriers, which work together to optimize the solubilization of APIs.

How Does It Work?

Upon ingestion, the tablet containing SEPITRAP™ disintegrates in the stomach’s acidic environment. The surfactant, adsorbed onto the porous carrier, desorbs rapidly—with at least 80% being released within five minutes. This desorption process enables the surfactant to form micelles around the API, significantly increasing solubility and facilitating absorption in the body.

A visual representation illustrates how SEPITRAP™ enhances the solubility of APIs, thereby improving bioavailability.

Benefits of SEPITRAP™

For Formulators:

1. Streamlined Manufacturing:
   • Enables direct compression, eliminating the need for intermediate wet granulation.
   • Simple blending with other powders, making the process user-friendly.
   • Reduces time and cost associated with traditional drug formulation methods.
2. Improved Bioavailability:
   • Enhances solubility of poorly soluble APIs.
   • Potentially increases drug release rates and stability.
   • Ensures rapid desorption of the surfactant (> 80% in 5 minutes).
   • Has no negative impact on tablet properties such as hardness and disintegration time.
   • Suitable for Hot Melt Extrusion (HME) to form Amorphous Solid Dispersions (ASDs).
     
3. SEPITRAP™ is suitable for acidic or enteric formulations.

For Patients:

• Supports the development of new drugs or patient-compliant dosage forms for poorly soluble APIs.
• Enhances drug efficacy by improving API solubility, leading to better bioavailability.

Precedence of Use

SEPITRAP™ has been successfully applied to various APIs, including:

• Atorvastatin
• Cefixime
• Clarithromycin
• Glimepiride

Sources

1. Nasrallah S., Alhadid A., Minceva M., Revealing the Solubility Enhancement of Active Pharmaceutical Ingredients through Eutectic Mixtures Formation: A Parameter Study, Crystal Growth & Design 2024, 24(15), 6364-6372. https://doi.org/10.1021/acs.cgd.4c00617
2. Van der Merwe, J., et al., The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability, Pharmaceutics 2020, 12, 393. https://doi.org/10.3390/pharmaceutics12050393
3. Bhalani, D.V.; Nutan, B.; Kumar, A.; Singh Chandel, A.K., Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics, Biomedicines 2022, 10, 2055. https://doi.org/10.3390/biomedicines10092055
4. Van der Merwe, J.; Steenekamp, J.; Steyn, D.; Hamman, J., The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability, Pharmaceutics 2020, 12, 393. https://doi.org/10.3390/pharmaceutics12050393

By leveraging SEPITRAP™, pharmaceutical professionals can optimize solid oral formulations, ensuring better solubility, improved bioavailability, and ultimately, enhanced therapeutic efficacy for patients.