Solid Dispersion-Based Compression-Coated Tablets of Efonidipine Hydrochloride Ethanolate: Enhancing Dissolution and Achieving Delayed Intestinal Release

Abstract

Aim

Efonidipine hydrochloride ethanolate (EHE), a BCS Class II calcium channel blocker, exhibits extremely poor aqueous solubility and undergoes aggregation in acidic conditions, resulting in limited and variable oral absorption. The present study aimed to develop and optimize a solid dispersion (SD)-based, compression-coated tablet of EHE designed to simultaneously enhance dissolution and deliver the drug after a controlled lag phase of approximately 4 h, thereby minimizing drug exposure to the gastric environment prior to rapid intestinal release.

Method

To address these challenges, this study developed a formulation strategy that combines an amorphous solid dispersion (SD) to enhance solubility with a time-controlled compression-coated tablet designed to provide a lag phase that minimizes drug exposure during gastric residence. SD prepared using PVP K25 achieved complete amorphization and markedly improved dissolution performance. The optimized SD was subsequently incorporated into a rapidly disintegrating core tablet surrounded by a hydrophilic–hydrophobic polymer coat engineered to produce a defined lag time. SDs were prepared by solvent evaporation at drug:polymer ratios of 1:3, 1:1, and 3:1 (using PVP K25 and Poloxamer 407) and characterized by PXRD, DSC, and FTIR. The optimized SD core was then compression-coated with varying proportions of HPMC K4M, ethyl cellulose (EC), and HPMC E15 across nine batches (C1–C9), and the resulting tablets were evaluated for hardness, drug content, in vitro dissolution (single- and two-stage), and release kinetics.

Results

PXRD confirmed complete loss of crystalline peaks at the 1:3 drug–polymer ratio, while DSC showed disappearance of the drug’s melting endotherm, indicating successful amorphization. The SD exhibited markedly improved dissolution compared to pure EHE, achieving rapid and sustained supersaturation without recrystallization. The optimized 1:3 SD released 54% within 30 min and reached 100% within 60 min, compared with <15% for pure EHE at 360 min, representing an approximately 6–7-fold increase in dissolution, and retained its amorphous state after 30 days at 40 °C/75% RH. Among the formulations evaluated, the optimized batch (C6) demonstrated a robust lag phase of approximately 4 hours with less than 10% drug release, followed by rapid and complete release (>90%) in the intestinal stage. In a two-stage study, C6 released only ~3–4% in 0.1 N HCl over the first 2 h. Release from C6 best fitted the Higuchi model (R² = 0.97) with a Korsmeyer–Peppas exponent of n = 0.46, indicating a predominantly diffusion-controlled mechanism. This profile significantly limits drug exposure to gastric pH during the lag phase while maximizing dissolution where absorption is most favorable. By integrating a 1:3 EHE:PVP K25 amorphous SD core (~6–7-fold dissolution enhancement) with an optimized 1:1 EC:HPMC E15 compression coat (C6), the platform delivered a reproducible ~4 h lag time (<10% release) followed by >90% intestinal release, simultaneously addressing the poor solubility and acid-aggregation of EHE.

Conclusion

This dual-mechanism design offers a scalable, pH-independent template for dissolution-limited, gastric-sensitive drugs, with in vivo pharmacokinetic and IVIVC studies identified as the next step to confirm its translational potential.

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Following excipients are mentioned in the study besides other: PVP K25, Poloxamer 407, HPMC K4M, ethylcellulose, HPMC E15

Source: Chauhan, S., Dudhat, K., Shah, S. et al. Solid Dispersion-Based Compression-Coated Tablets of Efonidipine Hydrochloride Ethanolate: Enhancing Dissolution and Achieving Delayed Intestinal Release. J Pharm Innov 22, 67 (2027). https://doi.org/10.1007/s12247-026-10939-7

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