Development and Optimization of Eudragit® EPO Coated Solid Dispersion-Based Immediate-Release Pellets of Drotaverine Hydrochloride for Pediatric use

Abstract

Purpose

The study aimed to develop a pediatric-friendly, immediate-release pellet formulation of Drotaverine Hydrochloride (DHC) to address issues related to poor aqueous solubility, bitter taste, and dosing flexibility in children. The objective was to enhance solubility and ensure rapid drug release while masking the bitter taste of drug.

Method

Solid dispersions of DHC were prepared using Polyethylene Glycol (PEG) 4000 and PEG 6000 via the solvent evaporation technique. These were converted into pellets using extrusion–spheronization, with MCC (Microcrystalline Cellulose), as the pelletizing agent and Eudragit^® EPO coating for taste masking. A 2³ factorial design was employed to optimize critical variables: spheronization speed, PEG type, and superdisintegrant concentration. The optimized batch was evaluated for physicochemical properties, disintegration, drug content, in vitro drug release in both gastric and oral pH, and kinetic modeling.

Results

The optimized formulation (DHP6) comprised a solid dispersion of DHC with PEG 4000 (1:2 ratio), 10% superdisintegrant, and a spheronization speed of 7000 rpm. It exhibited a pellet size of 0.78 ± 0.02 mm, t₈₅ of 15 ± 3.25 min, and disintegration time of 0.83 ± 0.04 min. The pellets showed excellent flowability (angle of repose: 12.04°; Hausner ratio: 1.01), friability (0.12 ± 0.004%), and acceptable hardness (0.55 ± 0.25 g/cm²). In vitro release studies demonstrated > 85% drug release within 15 min in 0.1 N HCl and negligible release in simulated salivary fluid, confirming effective taste masking. Release kinetics followed the Korsmeyer-Peppas model (R² = 0.9862), indicating diffusion-controlled release.

Conclusion

The developed immediate-release pellets of DHC offer improved solubility, rapid gastric release, and effective taste masking, making them a promising pediatric dosage form for abdominal pain management. The optimized formulation (DHP6) demonstrated robust physicochemical and performance characteristics, supporting its potential for pediatric use.