Physical isolation strategy in multi-layer self-nanoemulsifying pellets: Improving dissolution and drug loading efficiency of ramipril.

Background And Purpose: Liquid self-nanoemulsifying drug delivery systems (SNEDDS) face challenges related to stability, handling, and storage. In particular, lipophilic and unstable drugs, such as ramipril (RMP) and thymoquinone (THQ), face challenges in oral administration due to poor aqueous solubility and chemical instability. This study aimed to develop and optimize multi-layer self-nanoemulsifying pellets (ML-SNEP) to enhance the stability and dissolution of ramipril (RMP) and thymoquinone (THQ).

Methods: Liquid SNEDDS containing RMP and black seed oil (as a natural source of THQ) were prepared and characterized. The fluid-bed coating process was optimized by evaluating critical parameters such as inlet temperature, product temperature, air flow rate, atomizing air pressure, spray rate, and column height. Single-layer (SL-SNEP) and multi-layer (ML-SNEP) self-nanoemulsifying pellets were developed by applying various functional layers onto nonpareil sugar spheres. The pellets were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in vitro dissolution studies.

Results: Optimized fluid-bed coating parameters resulted in high coating recovery (>80%) and excellent mono-pellet percentages (≥97%). SEM analysis revealed well-defined, completely solidified layers in ML-SNEP. DSC and XRD studies suggested RMP amorphization. In vitro dissolution studies showed >86% RMP and THQ release within 60 minutes for both SL-SNEP and ML-SNEP. The physical isolation strategy significantly improved drug loading efficiency, with ML-SNEP showing 109% RMP loading efficiency compared to 55% in SL-SNEP. The addition of moisture sealing and anti-adherent layers had no negative impact on drug release, with SNEP-5L (including the anti-adherent layer) showing higher dissolution efficiency for both RMP and THQ.

Conclusion: This study successfully developed and optimized ML-SNEP as a novel approach for enhancing the stability and release of RMP and THQ. The physical isolation strategy was a key approach in enhancing drug loading efficiency while preserving the advantageous dissolution properties of liquid SNEDDS. This approach offers valuable insights for developing advanced oral drug delivery systems for poorly water-soluble and labile drugs.