Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, in vitro and in vivo Assessment

Conclusion: Talinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability. GRAPHICAL ABSTRACT Graphical Abstract. Self-nanoemulsifying drug delivery systems (SNEDDS) of talinolol (TAL) were developed using lipid formulation classification systems (LFCS) that improved the solubility and released the drug completely in dissolution media. In vitro toxicity studies with human red blood cells (RBC) showed that the SNEDDS formulations were non-toxic to human RBC. The oral bioavailability of TAL was significantly enhanced by the SNEDDS formulation in rats. Schematic Diagram: In vivo processes occurring after ingestion of SNEDDS formulations developed based on LFCS. Introduction Talinolol (TAL) [1-(4-cyclohexylureido-phenoxy)-2-hydroxy- 3-tert-butylaminopropane] (Figure 1) is a long-acting, highly selective β1 -adrenergic receptor antagonist which is incompletely absorbed in human from the upper small intestine (Schwarz et al., 2000; Siegmund et al., 2003). TAL (MW 363.49) is a moderately lipophilic molecule (log P: 3.2) with ionizable groups (pKa: 9.4). The solubility of TAL is pH dependent with low solubility at higher pH (0.02 mg/ml at pH 7.4, 37°C) (Trausch et al., 1995a). It has moderate lipophilic properties compared with other β-blockers (Trausch et al., 1995a;...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research