Rapid-onset sildenafil nasal spray carried by microemulsion systems:in vitroevaluation andin vivopharmacokinetic studies in rabbits

Abstract

An oleic acid-based microemulsion system with a member of the Tween series or Cremophor EL as the surfactant and a short-chain alcohol as the cosolvent was developed for rapid-onset intranasal delivery of sildenafil. The phase behaviour and solubilization capacity of the microemulsion system were characterized, and nasal absorption of sildenafil from the microemulsion formulations was investigated in rabbits. Sildenafil displayed a high solubility of 124 mg/mL in the microemulsion consisting of 40% oleic acid, 10% H(2)O, and 50% Tween 80:ethanol (EA) (at a 1:4 weight ratio). Nasal absorption of sildenafil from this microemulsion was found to be fairly rapid. With a 10-mg dose, the onset of action was arrived instantly following intranasal administration and the duration was over 3 h using an in vivo rabbit studies. In addition, nasal ciliotoxicity studies were carried out using in vivo rat nasal mucosa model and showed no ciliotoxicity. Therefore, the prepared systems are no serious nasal ciliotoxicity for intranasal administration. The microemulsion system composed of oleic acid, Tween 80, EA, and water may be a practical approach for the rapid-onset delivery of sildenafil for the treatment of erectile dysfunction.

Cystic fibrosis transmembrane conductance regulator activation by the solvent ethanol: implications for topical drug delivery

“…Images were analyzed using the Sisson-Ammons Video Analysis (SAVA) system version 2.1. 6 and virtual instrumentation software for CBF monitoring. All recordings were made at 200× magnification.…”

“…In terms of nasal delivery, several studies have reported the use of ethanol based microemulsions as a topical drug delivery system. 5,6 Short-chain alcohols such as ethanol have been used as the co-surfactant in microemulsions for intranasal topical drug delivery because the onset of drug activity is the fastest and the duration is the longest due to solubility being substantially enhanced by ethanol. 6 During testing of candidate CFTR modulators, we serendipitously discovered low concentrations of ethanol in the control vehicles produce robust activation of wild type CFTR-mediated Cl − transport in well characterized primary cell culture models of murine nasal septal (MNSE) and human sinonasal respiratory epithelium (HSNE).…”

“…5,6 Short-chain alcohols such as ethanol have been used as the co-surfactant in microemulsions for intranasal topical drug delivery because the onset of drug activity is the fastest and the duration is the longest due to solubility being substantially enhanced by ethanol. 6 During testing of candidate CFTR modulators, we serendipitously discovered low concentrations of ethanol in the control vehicles produce robust activation of wild type CFTR-mediated Cl − transport in well characterized primary cell culture models of murine nasal septal (MNSE) and human sinonasal respiratory epithelium (HSNE). Enhancing transepithelial Cl − secretion with low concentrations of a common and safe vehicle (already present in numerous aerosolized pharmaceuticals) represents a reasonable therapeutic approach to treatment of mucociliary dysfunction.…”

Rapid-Onset Sildenafil Sublingual Drug Delivery Systems: In Vitro Evaluation and In Vivo Pharmacokinetic Studies in Rabbits

“…According to our previous work, 21 the stability of sildenafil sublingual spray-incorporating MEs was studied via their clarity and phase separation. The solubilization capacities of the sublingual spray for sildenafil were investigated by HPLC as described.…”

Clinical Experience of Cancer Immunotherapy Integrated With Oleic Acid Complexed With De-Glycosylated Vitamin D Binding Protein

“…Because of the complexing of the protein with the fatty acid hydrophobic moiety together with the wellknown properties of OA as an absorption enhancer, OA-GcMAF complexes could also be administered sublingually (Cui et al, 2005;Sakata et al, 2011), as an aerosol with a common nebuliser (Lu et al, 2011), or as suppositories (Goto et al, 1991).…”