FORMULATION AND EVALUATION OF IVABRADINE HYDROCHLORIDE LOADED TRANSFERSOMAL GEL FOR TRANSDERMAL DELIVERY
Objective: Aim of this study was to develop the topical delivery containing ivabradine hydrochloride (IVH) loaded transpersonal gel for symptomatic treatment of chronic stable angina pectoris in coronary artery disease.
Methods: Different hydrophilic-lipophilic balance (HLB) values of surfactants-tween-80, span-80 and sodium deoxycholate (SDC) were investigated to prepare transfersomes (TFs)respectively, with different concentration of soya phosphatidylcholine and 10% v/v ethanol in phosphate buffer solution (pH 6.8) by conventional rotary evaporation sonication method. The prepared formulations were evaluated for percentage entrapment efficiency (%EE), deformability index (DI), turbidity, vesicle shape and size, in vitro drug release study and stability. SEM was done on selected formulation F8 and liposome formulation (LF). Gel was prepared by using carbopol-940 as a gelling agent with propylene glycol, polyethylene glycol solution as permeation enhancer by 32 factorial design optimization methods. The developed gel was evaluated for pH, viscosity, drug content, ex-vivo permeation studies and stability studies of TFs-gel. This was compared with LF-gel prepared by same procedure.
Results: Maximum % EE (78.4±0.94), suitable vesicular size (128.6 nm) and maximum DI (34.9±1.9) was found in TFs-TW-80 and selected for gel development. In vitro drug release data from TFs-TW-80, plain drug solution and liposomal formulation (LF) revealed that % cumulative drug released in TFs-TW-80 was found maximum (89.5±0.12 %) in 20 min than others. It was 2.1 times higher than LF and 3.3 times higher than the plain drug. SEM study showed spherical shape of vesicles. The drug contents in the TFs and LF gels were found to be 92 to 95%w/w. Partition coefficient for TFs-loaded gel was 1.04±0.03. Ex vivo permeation study from hairless rat skin showed that permeation of drug is described by firstly first-order kinetics than zero-order kinetics. The drug released from TFs-gel was found to be 1.7 times higher than LF-gel and about 1.9 times higher than plain drug. Flux from TFs-gel was 2.04 times greater than LF-gel and 3.28 times more than plan drug. Stability studies indicated that suitable storage condition for developed gel was temperature 25 °C or less, where the pH, potency and therapeutic efficacy of formulations remain constant.
Conclusion: Thus, transdermal route has become one of the most successful and innovative focus for research in drug delivery of IVH loaded TFs-TW-80 to increase stability and bioavailability.
2. Kundlik G, Pal R. Potential role of transfersomes in transdermal drug delivery. World J Pharma Res 2014;1:21-38.
3. Acharya A, GBKK, Ahmed MG, Paudel S. A novel approach to increase the bio availability of candisartal cilixetil by proniosomal gel formulation: in vitro and in vivo evaluation. Int J Pharm Pharm Sci 2016;8:241-6.
4. Modi CD, Bharadia PD. Transferosomes: new dominants for transdermal drug delivery. Am J Pharm Tech Res 2012;2:72-91.
5. Prausnitz MR, Langer SR. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discovery 2004;3:115-24.
6. 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.
7. 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.
8. Laxmi A, Premchandani, Sunil R, Bakliwal, Rane B, Nayan A, et al. Formulation of protransfersomal gel of diclofenac potassiumand its in vitro characterization. Indian J Drugs 2016;4:129-40.
9. 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.
10. Jain SK, Gupta Y, Jain A, Rai K. Enhanced transdermal delivery of acyclovir sodium via elastic liposomes. Drug Delivery 2008;15:141-7.
11. Montgomery DC, Design and analysis of experiments. 4 Ed. John Wiley and Sons, New York; 1996.
12. 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.
13. Gondaliya DP, Pundarikakshudu K. Preparation, characterization and transdermal permeation of nimesulide from aqueous gel and emulgel. Indian Drugs 2002;39:465-73.
14. Renata FV, Lopez, John HC, Vitoria M, Bentley LB. Influence of cyclodextrin complexation on the in vitro permeation and skin metabolism of dexamethasone. Int J Pharm 2000;200:127-32.
15. Fayez SM, Gad S, Khafagy EA, Jaleel GAA, Ghorab MM, El-Nahhas SA. Formulation and evaluation of ethodolac lecithin organogel transdermal delivery systems. Int J Pharm Pharm Sci 2015;7:325-34.
16. Hadgraft J, Guy H. Transdermal drug delivery. Eds. Marcel dekker, Inc. New York; 1991. p. 292.
17. Banakar UV. Pharmaceutical dissolution testing. Eds. Marcel Dekker, Inc. New York; 1991. p. 294.
18. Schreier H, Bouwstra JA. Liposomes and niosomes as topical drug carriers: Dermal and transdermal drug delivery. J Controlled Release 1994;30:1–15.
19. Jain S, Jain N, Bhadra D, Tiwari AK, Jain NK. Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation. Curr Drug Delivery 2005;2:222–33.
20. 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.
21. Scognamiglio I, De Stefano D, Campani V. Nanocarriersfor topical administration of resveratrol: a comparative study. Int J Pharm 2012;440:179-87.
22. Boltan S. Factorial designs. In: Pharmaceutical statistics: Practical and clinical applications. 3 Ed. Marcel Dekker Inc. New York; 1997. p. 10-72.
23. Laouini A, Jaafar Maalej C, Sfar S. Liposome preparation using a hollow fiber membrane contact ore application to spironolactone encapsulation. Int J Pharm 2011;415:53-61.
24. Cevc G, Vierl U, Mazgareanu S. Functional characterization of novel analgesic product based on self-regulating drug carriers. Int J Pharm 2008;360:18-28.
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