Taste-masked pellets of sodium warfarin prepared by hot melt extrusion – ECP 2025 Poster

This poster was presented at the ECP 2025 in Porto

Introduction

Fig. 1. 20% drug-loaded particle microscopy before (A) and after (B) 360 minutes of thermal treatment, magnification (40x)

Fig. 1. 20% drug-loaded particle microscopy before (A) and after (B) 360 minutes of thermal treatment, magnification (40x)

Warfarin, a coumarin derivative, is an indirect-acting anticoagulant and a vitamin K antagonist [1].

The main challenges and limitations of warfarin use include the risk of bleeding from improper dosing and its bitter taste [1].

This study investigated an alternative approach for personalising warfarin dosing by developing taste-masked multiple unit pellets (MUP) using hot melt extrusion (HME) and thermal treatment.

The effects of varying drug loads (10, 20, and 30 wt. %) on the duration of post-processing thermal treatment to achieve the desired aspect ratio (AR) and drug release were examined.

Methods

Materials

Warfarin sodium clathrate (WSC, Alchymars Icm SM Private Ltd., Tamil Nadu, India); Methyl methacrylate and diethylaminoethyl methacrylate copolymer (Kollicoat® Smartseal 100P; BASF SE, Ludwigshafen, Germany); glass beads (60 mesh/250μm); Hydrochloric acid, potassium phosphate monobasic, sodium phosphate dibasic dihydrate and phosphoric acid (pharmaceutical grade, used as received).

Results

Thermal treatment of the filament particles reduces their length and increases their diameter due to the elastic deformation of the polymer macromolecules. After cutting, the particles have sharp edges (Fig. 1 A), but thermal treatment brings their aspect ratio (AR) closer to 1, visibly enhancing their smoothening (Fig. 1 B).

Fig. 2. The dissolution profile of 30 % drug-loaded filament particles

The particle’s surface area and volume were calculated based on the cylinder geometry. The total surface area (tSA) was then divided by the total volume (V) to obtain the total surface area-to-volume ratio (tSA/V). The highest dissolution rate in 0.1 M HCl is observed in samples with larger tSA/V ratios (Fig. 2). After 60 minutes, drug release reaches at least 80% in all cases, indicating that this formulation is not a good fit for an immediate-release dosage form. No significant dissolution was observed in PBS.

The correlation between elastic modulus and drug loading for filament samples is nearly linear (R² = 0.9769) (Fig. 3).

Figure 4 shows a clear correlation between drug loading and the time required to reach 50% drug release. However, no correlation is observed between the tSA/V ratio and the time necessary to reach 50% drug release.

Conclusion

Fig. 4. The time needed to achieve 50 % of the drug release as a function of drug loading and surface area-to-volume ratio (SA/V, cm2/cm3) — **Fig. 4.** The time needed to achieve 50 % of the drug release as a function of drug loading and surface area-to-volume ratio (SA/V, cm2/cm3)

As the drug loading in the filament increases, so does its elastic modulus, which limits the elastic deformation of polymer macromolecules. Decreased elasticity raises the thermal treatment duration required to achieve an AR of 1.
Higher drug loading enhances the dissolution rate, which shortens the time needed to reach 50% drug release. Such correlation for surface area-to-volume (tSA/V) ratio was not obtained.

After the cutting and thermal treatment, the particle edges become smoother, contributing to a more rounded particle shape, which should be beneficial for mouthfeel and medical compliance.

This concept is suitable for producing taste-masked MUP pellets, but further investigation is required.

See the full poster on Taste-masked pellets of sodium warfarin prepared by HME here

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Source: Paula KAUFELDE, Andrejs ANISKEVICS, Jevgenijs SEVCENKO, Marta ZOGOTA, Valentyn MOHYLYUK, poster Taste-masked pellets of sodium warfarin prepared by hot melt extrusion, Riga Stradins University, Leading Research Group, Faculty of Pharmacy, ECP 2025 Porto

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