Formulation and Evaluation of Thienorphine Hydrochloride Sublingual Delivery System

Abstract

Thienorphine hydrochloride (ThH) is a highly insoluble and readily metabolized partial-opioid agonist. It is used for the treatment of pain and heroin addiction. This study aimed to formulate and evaluate sublingual delivery systems containing ThH. Dimethyl-β-cyclodextrin (DM-β-CD) can enhance the solubility and permeability of hydrophobic drugs. In this paper, ThH cyclodextrin inclusion complexes were prepared and administrated sublingually with the objective of improving the drug's aqueous solubility, in vitro permeation rate, and in vivo absorption rate. The formulation was prepared with DM-β-CD using the freeze-dried method and characterized using phase solubility, differential scanning calorimetry (DSC), X-ray and NMR analyses. The results of each test indicated the formation of dynamic inclusion complexes between ThH and DM-β-CD. The inclusion complexes also showed significant increases in in vitro aqueous solubility and mucosal permeability. According to the pharmacokinetic study of the complex in rats, the AUC and C max values of the sublingual delivery group were 40 and 46 times higher than those of the gastrointestinal group, whereas t max was shorter, which proved that in vivo absorption and metabolism had been improved. It can therefore be concluded that the inclusion technology and sublingual delivery system were suitable for ThH development.

Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically based pharmacokinetic model for YQA‐14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction

“…Phosphate buffer (1 m , pH 7.4) and oil ( n ‐octanol) were used as the partition phases. The result was calculated by the following equation: where Conc initial is the concentration of compound in the initial aqueous solution at the starting of experiment, Conc final is the concentration of compound in the final aqueous phase after experiment, V aq is the volume of aqueous solution and V oct is the volume of n ‐octanol .…”

“…where Conc initial is the concentration of compound in the initial aqueous solution at the starting of experiment, Conc final is the concentration of compound in the final aqueous phase after experiment, V aq is the volume of aqueous solution and V oct is the volume of n-octanol [18,19].…”

Salivary lactoferrin is transferred into the brain via the sublingual route

“…bLF powder (5 mg; LKT Laboratories, Inc., St. Paul, MN, USA) was administered to male seven-week-old Wistar rats (body weight 200-250 g) via the sublingual mucosa under deep anesthesia. The administration method was modified from that of a previous study 21) to administer a suitable amount of powder underneath the tongue using a spoon. As a control, the rats were administered bovine serum albumin (5 mg; Sigma, St. Louis, MO, USA).…”