The Future of Oral Biologics: Solid Sedds Powered by NEUSILIN® UFL2

Introduction

Self-emulsifying drug delivery systems (SEDDS) have emerged as a promising approach for enhancing the oral bioavailability of challenging therapeutic compounds, particularly biopharmaceuticals like proteins and peptides.

A study published in “Pharmaceutics” journal showcases an innovative application of Quality by Design (QbD) principles to develop a solid SEDDS formulation for the oral delivery of lysozyme, with Neusilin® UFL2 playing a crucial role as the solid carrier.

The Challenge of Oral Protein Delivery

Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of various diseases due to their high specificity and safety. However, their oral delivery remains a significant challenge in pharmaceutical development:

Harsh gastrointestinal environment
Enzymatic degradation
Poor permeability across the intestinal epithelium

Are major obstacles that limit the oral bioavailability of these large, hydrophilic molecules.

How to Solve the Problem

SEDDS: A Promising Solution

Self-emulsifying drug delivery systems (SEDDS) have shown great potential in addressing these challenges. SEDDS are isotropic mixtures of oils, surfactants, and co-solvents that spontaneously form fine oil-in-water emulsions upon gentle agitation in an aqueous environment. This unique property makes them ideal for oral delivery, as they can protect sensitive molecules from degradation and enhance their absorption.

Innovative Approach: Hydrophobic Ion Pairing

The study employed a clever strategy to incorporate lysozyme, a hydrophilic protein, into the lipophilic SEDDS formulation. By using hydrophobic ion pairing (HIP), the researchers complexed lysozyme with sodium dodecyl sulfate (SDS), an anionic surfactant. This approach increased the lipophilicity of lysozyme, facilitating its incorporation into the SEDDS.

Quality by Design: Ensuring Robust Development

The researchers utilized the Quality by Design (QbD) approach to systematically develop and optimize the SEDDS formulation. This methodology involved:

Defining the Quality Target Product Profile (QTPP)
Identifying Critical Quality Attributes (CQAs)
Determining Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs)
Performing risk assessment
Applying Design of Experiments (DoE)
Establishing the Design Space
Defining the control strategy

This systematic approach ensured a thorough understanding of the formulation and process variables, leading to a robust and optimized product.

From Liquid to Solid: The Role of Neusilin® UFL2

A liquid SEDDS formulation was converted into a free-flowing powder via adsorption onto a solid carrier, a technique known for high lipid uptake and content uniformity. In this study, silicon dioxides (Syloid® 244 FP and Syloid® AL-1 FP) and magnesium aluminometasilicate (Neusilin® UFL2) were evaluated. Preliminary studies showed that Neusilin® UFL2 had the highest adsorption capacity (2:1). Syloid® AL-1 FP was excluded due to its poor oil loading. Neusilin® UFL2 and Syloid® 244 FP were selected for further study. The maximum dry powder ratio for Neusilin® UFL2 was foundto be 1:2 (carrier : liquid SEDDS).

While liquid SEDDS showed promising results, the researchers took a step further by developing a solid SEDDS formulation. This is where Neusilin® UFL2 played a crucial role. As a highly porous magnesium aluminometasilicate, Neusilin® UFL2 served as an excellent solid carrier for the liquid SEDDS.

The advantages of using Neusilin® UFL2 in this application include:

High specific surface area: Allows for efficient adsorption of the liquid SEDDS
Excellent flow properties: Facilitates further processing into tablets
Chemical inertness: Ensures stability of the adsorbed formulation
High loading capacity: Enables a compact final dosage form

The researchers compared Neusilin® UFL2 with other potential carriers, including Syloid 244 FP and Syloid AL-1 FP. Neusilin® UFL2 at a 1:1 ratio with 35% w/w SEDDS loading in the tablet was the only suitable one to produce self-emulsifying tablets with acceptable properties. Syloid®244FP failed to produce adequately hard tablets, likely due to lipid “squeeze-out” from the carrier pores, where increased liquid load reduces tablet hardness.

Neusilin® UFL2 demonstrated superior performance in terms of flow properties and compressibility, making it the ideal choice for the solid SEDDS formulation.

Continue reading and see the full Pharmaceutical Technical Newsletter on The Future of Oral Biologics: Solid Sedds Powered by NEUSILIN® UFL2 here:

(click the picture to download the technical newsletter)

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