Background: Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet. Methods: The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid ® and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies. Results: Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid ® at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant ( P <0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies. Conclusion: RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.

The current study evaluates the Ultra High performance Liquid Chromatography (UHPLC) method for the quantification of Ramipril in lipid-based formulations. A reliable, highly precise, more specific and reproducible reversed phase UHPLC method has been developed and validated according to the regulatory guidelines, which was composed of isocratic mobile phase; acetonitrile and 0.25% formic acid solution in ratio of (40:60 %V/V) with a flow rate of 0.2 mL/min, and C18 column (2.1×50 mm, 1.7 µm). The detection was carried out at 210 nm. The developed UHPLC method was found to be rapid (3 min. run time), selective with high resolution of Ramipril peak (1.4 min.) from different lipid matrices and highly sensitive (Limit of Detection and Lower Limit of Quantification were 0.034 µg/mL and 0.199 µg/mL, respectively). The linearity, accuracy and precision were determined as acceptable over the concentration range of 1 -200 µg/mL for Ramipril. The results showed that the proposed UHPLC method can be used for the estimation of Ramipril in lipid-based formulation by indicating its purity and stability with no interference of excipients or related substances of active pharmaceutical ingredient.