<p>Self-nanoemulsifying ramipril tablets: a novel delivery system for the enhancement of drug dissolution and stability</p>

Abstract

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.

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine

“…The solid SNEDDS characterization revealed the presence of the CUR and PP in a molecularly dissolved amorphous state, within the SNEDDS formulation. These data confirm that both CUR and PP were completely solubilized within S-SNEDDS and that the solidification process did not trigger drug precipitation [13,41]. In addition, there was no obvious sign of chemical interaction between the drugs and the formulations.…”

“…In contrast, all the CUR-PP loaded S-SNEDDS showed complete absence of CUR and PP diffraction peaks. Therefore, XRPD data together with DSC data supports that CUR and PP were transformed into an amorphous state within solid SNEDDS [13,40].…”

“…Various CUR-PP loaded L-SNEDDS were prepared and the most potential candidates were solidified using the two adsorbents A300 and NUS. In order to obtain an optimum SNEDDS formula, six formulations were screened against their droplet size, zeta potential and equilibrium drug solubility parameters [13]. CUR and PP are poorly-water soluble drugs with partition coefficient values; logp ≈ 3 and 2.25, respectively [17,46].…”

“…Self-emulsifying, microemulsifying and nanoemulsifying drug delivery systems (SEDDS/SMEDDS/SNEDDS) are highly effective in enhancing the aqueous solubility, dissolution and bioavailability of poorly-water soluble drugs [13,14]. These lipid-based systems are composed of isotropic mixtures of oils, surfactant, cosurfactants and/or cosolvents.…”

“…Upon drug loading within the SNEDDS and subsequent solidification with adsorbents, CUR and PP peaks were completely disappeared from all the tested solid SNEDDS. Due to the low drug concentration within solid SNEDDS, it was difficult to decide whether the CUR and PP peaks disappearances were owing to drug transformation into an amorphous state or to significant drug dilution within the formulation [13,40].…”