Preparation and evaluation of valsartan by a novel semi-solid self-microemulsifying delivery system using Gelucire 44/14

Abstract

The aim of the present study was to develop a novel semi-solid self-microemulsifying drug delivery system (SMEDDS) using Gelucire(®) 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire(®) 44/14 (oil), 40% Solutol(®) HS 15 (surfactant), and 30% Transcutol(®) P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 ± 1.43 and 33.34 ± 2.15 nm, and the melting points of them were 35.6 and 36.8 °C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0-t after oral administration in rats, respectively. These results indicated that the novel semi-solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature.

Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

“…The reference drug, Diovan ® , showed similar pharmacokinetic behavior to raw VST throughout the whole time period, except for the peak time around 1.5–2 h. In comparison, the S-SuSMED tablets showed a sharp increase within 1 h, even though the plasma VST level of S-SuSMED-T2 was somewhat higher than that of S-SuSMED-T1. This rapidly increasing pattern, as reported in earlier literature [9,11,15], might be attributed to not only the VST dissolution enhancement of S-SuSMED in the acidic environment of the stomach but also the increased permeation of VST through the GI tract due to nano-sized emulsions [41].…”

“…Gelucire ® 44/14 (lauroyl polyoxyl-32 glycerides; GEL) is an inert semi-solid waxy material with a melting point of 44 °C and an HLB value of 14. It was recently introduced as a self-emulsifying non-ionic surfactant, and thus is frequently used in type III lipid-based formulations including SMEDDS [10,11]. This excipient offers broad use flexibility: in addition to filling hard or soft gelatin capsules, it may also be used to make pellets, spheroids, or matrix forms [12,13].…”

“…This excipient offers broad use flexibility: in addition to filling hard or soft gelatin capsules, it may also be used to make pellets, spheroids, or matrix forms [12,13]. Employing GEL, improvement of the dissolution and BA of numerous water-insoluble drugs has been successfully achieved [11,14]. As GEL contains a well-balanced proportion of short-, medium-, and long-chain fatty acid esters, it forms an exceptionally stable, fine dispersion when in contact with the GI fluids at body temperature.…”

Amelioration of lipophilic compounds in regards to bioavailability as self-emulsifying drug delivery system (SEDDS)

“…Higher concentrations of surfactant are required for the optimum formulation of SEDDS, but this higher concentration may lead to the drug precipitation [48]. Therefore, co-solvents are added to lower the surfactant concentration and maintain the uniformity of the formulation [4,49].…”

Analysis of the Improvement of Termination Property of VALSARTAN using Solvent Deposited Systems

“…erratic amalgamation important to slow down oral bioavailability 3 . Till date several approaches has been developed to improve the suspension properties of weakly soluble drugs like complexation, solid dispersions, and soft gels [4][5][6][7] . Solvent deposited systems (SDS) in view of powder arrangement innovation demonstrates capable probable in humanizing the disintegration pace of inadequately solvent medications like VAL.…”