A COMPARATIVE ASSESSMENT OF VESICULAR FORMULATIONS: TRANSFERSOMES AND CONVENTIONAL LIPOSOMES LOADED IVABRADINE HYDROCHLORIDE
Keywords:Ivabradine, Ivabradine hydrochloride, Vesicles, Conventional liposomes, Transfersomal preparations
Objective: Ivabradine hydrochloride (IH), a benzazepine derivative used to treat cardiovascular disease angina pectoris. In this study IH-loaded novel carrier systems transfersomes (TFs) and conventional liposomes (CLs) were developed and compared for their efficacy to enhance the stability of drugs from degradation.
Methods: TFs formulations (TF-1, TF-2 and TF-3) were prepared by using different biocompatible surfactants; tween-80 (TW), span-80(S) and sodium deoxycholate (SC) in the concentration ratio of 15 parts with 85 parts of soy phosphatidylcholine as phospholipid by thin-film hydration method. These vesicles were compared with CLs formulation (L-1) prepared in 7:3 molar ratio of soy phosphatidylcholine: cholesterol by following the same method. These vesicles were compared for physical appearance, vesicle shape, and size, percentage drug entrapment efficiency (%DEE), deformability index (DI), in vitro percentage cumulative drug release study, and physical stability studies. The chosen optimized novel carriers were observed under scanning electron microscopy.
Results: The compared data demonstrated that the physical appearance for all vesicles was turbid and had a spherical shape. The size distribution was in the range of 129.0 nm to 273.5 nm in vesicles. The %DEE (79.0±0.94) and DI (35.0±1.9) was found maximum in TF-1 formulation that was 2.3 times higher than L-1 formulation. The in vitro percentage cumulative drug release study followed second-order polynomial kinetics that was 2.0 times higher than L-1and 2.9 times higher than the plain drug in 30 min (90.4±0.06%) from TF-1. The vesicles were found to be stable at refrigeration conditions.
Conclusion: Thus, amongst of all vesicles TW loaded TFs (TF-1) was chosen as an excellent novel vesicular carrier for hydrophilic drugs due to its higher deformability behavior than CLs that protects the certain drugs from biodegradation and provides stability.
Thollon C, Vilaine JP. If inhibition in cardiovascular diseases. Adv Pharmacol 2010;59:53–92.
Dillinger JG, Maher V, Vitale C, Henry P, Logeart D, Manzo SS, et al. Impact of ivabradine on central aortic blood pressure and myocardial perfusion in patients with stable coronary artery disease. Hypertension 2015;66:1138–44.
Tagliamonte E, Cirillo T, Rigo F, Astarita C, Coppola A, Romano C, et al. Ivabradine and bisoprolol on doppler-derived coronary flow velocity reserve in patients with stable coronary artery disease: beyond the heart rate. Adv Ther 2015;32:757–67.
Mangiacapra F, Colaiori E, Ricottini E, Balducci F, Creta A, Demartini G, et al. P6291: heart rate reduction by ivabradine for improvement of endothelial function in patients with coronary artery disease: the randomized open-label RIVENDELL study. Eur Heart J 2015;36 Suppl 1:1105.
Gloeckler S, Traupe T, Stoller M, Schild D, Steck H, Khattab A, et al. The effect of the heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014;100:160–6.
Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005;26:2529–36.
Kim A, Lee EH, Choi SH, Kim CK. In vitro and in vivo transfection efficiency of a novel ultra deformable cationic polymer. Biomaterials 2004;25:305–13.
Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharma 2007;332:1–16.
Arciriegas SM, Bernad MJ, Caballero SC, Hernandez D, Solis B, Vargas D. Process for physicochemical improvement of ultra-flexible liposomes loaded with insulin. Indian J Pharm Sci 2019;81:110-6.
Hanan M, Laity EI, Omar S, Laila G. Novel sugar esters proteasomes for transdermal delivery of vinpocetine: preclinical and clinical studies. Eur J Pharm Biopharm 2011;77:43-55.
Panda S, Patra S. Rapid and Selective UV Spectrophotometric and RP-HPLC methods for dissolution studies of ivabradine controlled-release formulations. PharmaTutor 2014;2:201-13.
Gupta A, Aggrawal G, Singla S, Arora R. Transfersomes: a novel vesicular carrier for enhanced transdermal delivery of sertraline: development, characterization, and performance evaluation. Sci Pharm 2012;80:1061–80.
Laxmi A, Premchandani, Sunil R, Bakliwal, Bhushan, Rane, et al. Formulation of protransfersomal gel of diclofenac potassium and its in vitro characterization. Indian J Drugs 2016;4:129-40.
Princely S, Dhanaraju MD. Design, formulation, and characterization of liposomal-encapsulated gel for transdermal delivery of fluconazole. Asian J Pharm Clin Res 2018;11:417-24.
Jain SK, Gupta Y, Jain A, Rai K. Enhanced transdermal delivery of acyclovir sodium via elastic liposomes. Drug Delivery 2008;15:141-7.
Duplessis J, Ramachandran C, Weiner N, Muller D, Müller DG. The influence of lipid composition and lamellarity of liposomes on the physical stability of liposomes upon storage. Int J Pharm 1996;127:273–8.
Wei L, Chuqin Y, Huaqing Lin, Xiaoyuan Z. Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo. Asian J Pharma Sci 2013;8:336-45.
Lichtenberg D, Opatowski E, Kozlov MM. Phase boundaries in mixtures of membrane-forming amphiphiles and micelle-forming amphiphiles. Biochim Biophys Acta 2000;1508:1-19.
Scognamiglio I, De Stefano D, Campani V. Nanocarriers for topical administration of resveratrol: a comparative study. Int J Pharm 2012;440:179-87.
Abdallah MH. Transfersomes as a transdermal drug delivery system for enhancement of the antifungal activity of nystatin. Int J Pharm Pharm Sci 2013;5:560-7.
Benson HA. Transfersomes for transdermal drug delivery. Expert Opin Drug Delivery 2006;3:727-37.