Customized Enteric Capsules Enabling High-Load Sodium Caprate Formulations for Oral Delivery of Large Molecules

Introduction

Oral delivery of emerging drug modalities such as peptides, PROTACs, and siRNA is hindered by low intestinal permeability and instability in the GI tract, leading to parenteral administration and poor adherence. Enteric Capsugel® Enprotect® capsules enable targeted intestinal release1-3. Combined with permeation enhancers such as sodium caprate (C10), they could offer a scalable approach to improve oral bioavailability. This study aims to develop a scalable C10-based formulation and design a customized enteric capsule with preserved enteric performance with high C10 loading.

Methods

Material

Optimized C10 was kindly provided by Ashland. Vivapur®102 (MCC) was provided by JRS and magnesium stearate (MgSt) was acquired from Sigma. Size #0 Capsugel® Enprotect® capsules were manufactured at industrial scale.

Formulation preparation

C10 (70%) was first blended with MCC (29.5%) during 10 min at 49 rpm using a Turbula® mixer (Erweka). MgSt (0.5%) was added to the preblend and mixed at 100 rpm for 2 additional min.

C10 and formulation characterization

The compressibility, flowability, and ability to form a plug suitable for encapsulation into size #0 capsules of C10 and its formulation were evaluated using a tapped density tester (SVM II), a flow tester (Erweka GT), a powder rheometer (FT4), and a slug tester (Sauter), respectively.

Disintegration test

The ability of capsules filled with high C10 levels to retain their enteric properties was evaluated by disintegration (Apparatus B) for 2 hours in buffer 0.1N HCl, followed by buffer pH 6.8.

Dissolution test

Enteric performance of the innovative capsule was evaluated through dissolution test using Esomeprazole (EMT), an acid sensitive model API, in a USP apparatus type II (paddle).

Capsule manufacturing and charactization

Results

Table 1. Characteristics od pure C10 and developed formulation (NA=Not Applicable)

Improved formulation for taping capsule filling

C10 was characterized and its properties were improved for tamping capsule filling with a formulation containing 70% C10, 29.5% MCC and 0.5% MgSt , Table 1. The optimized blend exhibited better flow and stability, Table 1, and slug testing confirmed suitability for size 0 capsule filling (~190 mg C10 per capsule), Fig. 5.

See the full technical brochure on Customized Enteric Capsules here

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Customized Enteric Capsules Enabling High-Load Sodium Caprate Formulations for Oral Delivery of Large Molecules

Source: Capsugel, Camille Dumont, Marine Agisson, Serena Corsil, Céline Kientz, Delphine Nombret, Vincent Jannin, technical brochure Customized Enteric Capsules