NIOSOME-ENCAPSULATED CLOMIPRAMINE FOR TRANSDERMAL CONTROLLED DELIVERY
Keywords:
Clomipramine hydrochloride, Antidepressant, Niosomes, Niosomal gel, HPMC, TransdermalAbstract
ABSTRACT
Clomipramine (CLM) is a highly selective inhibitor of serotonin reuptake antidepressant. The objective of the present research was to decrease the extensive first-pass metabolism of the drug in the liver by developing and optimizing niosomal transdermal formulation of CLM in order to improve its bioavailability. Niosomes were prepared according to      4 × 22 factorial design where surfactant type was set at four levels (Tween 20, Tween 60, Span 20 and Span 60), surfactant to cholesterol ratio at two levels (1:1, and 1:0.5) and charge inducing agent (dicetyl phosphate) at two levels (present and absent). Entrapment efficiency (%EE) and release efficiency percentage after 6 h (RE6 %) were chosen as dependent variables. CLM loaded niosomes were prepared by employing a thin film hydration technique using different non-ionic surfactants (Tween 20, Tween 60, Span 20 or Span 60), in the presence of cholesterol and a negative charge inducer dicetyl phosphate (DP) in different molar ratios. The prepared niosomes were characterized for entrapment efficiency, shape, size, zeta-potential and in vitro drug release. The studies demonstrated successful preparation of CLM niosomes. Niosomes showed percentage entrapment efficiency (%EE) of 72.54 ± 0.37 % for optimized formula (F5) which composed of (1:1:0.1 molar ratio of Tween 60, cholesterol and DP) and 25 mg of CLM. The selected formula F5 (1:1:0.1) was incorporated in gel base of HPMC-K15M (4%) and evaluated through in vitro release. Skin irritancy test performed on albino rats, showed no sign of irritation.
Downloads
References
Verma P, Chandak R. Development of matrix controlled transdermal delivery systems of pentazocine: in vitro/in vivo performance. Acta Pharm. 2009; 59:171-186.
Pavelic Z, Skalko-Basnet N, Schubert R. Liposomal gels for vaginal drug delivery. Int. J. Pharm. 2001; 219: 139-149.
Chandak AR, Verma PRP. Design and development of hydroxypropyl methycellulose (HPMC) based polymeric films of methotrexate: physicochemical and pharmacokinetic evaluations. Yakugaku Zasshi. 2008; 128:1057-1066.
Valenta C, Auner BG. The use of polymers for dermal and transdermal delivery. Eur. J. Pharm. Biopharm. 2004; 58:279-289.
Manosroi A, Khanrin P, Lohcharoenkal W, Werner RG, Friedrich G, Manosroi W, Manosroi J. Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int. J. Pharm. 2010; 392:304-310.
Manconi M, Sinico C, Donatella V, Loy G, Fadda AM. Niosomes as carriers for tritenoin. I. Preparation and prosperities. Int. J. Pharm. 2002; 234:237-248.
Bal SM, Ding Z, van Riet E, Jiskoot W, Bouwstra JA. Advances in transcutaneous vaccine delivery: do all ways lead to Rome? J. Control.Release. 2010; 148:266-282.
Dufes C, Gaillard F, Uchegbu IF, Schätzlein AG, Olivier JC, Muller JM. Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain. Int.J.Pharm. 2004; 285:77-85.
Rentel CO, Bouwstra JA, Naisbett B, Junginger HE. Niosomes as a novel peroral vaccine delivery system. Int. J. Pharm. 1999; 186, 161-167.
Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int. J. Pharm. 2005; 306:71-82.
Marianecci C, Paolino D, Celia C, Fresta M, Carafa M, Alhaique F. Nonionic surfactant vesicles in pulmonary glucocorticoid delivery: characterization and interaction with human lung fibroblasts. J. Control. Release. 2010; 147:127-135.
Alsarra IA, Bosela AA, Ahmed SM, Mahrous GM. Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur. J. Pharm. Biopharm. 2005; 59:485-490.
Muzzalupo R, Tavano L, Cassano R, Trombino S, Ferrarelli T, Picci N. A new approach for the evaluation of niosomes as effective transdermal drug delivery systems. Eur. J. Pharm. Biopharm. 2011; 79: 28-35.
Manconi M, Caddeo C, Sinico C, Valenti D, Mostallino MC, Biggio G, Fadda AM. Ex vivo skin delivery of diclofenac by transcutol containing liposomes and suggested mechanism of vesicle–skin interaction. Eur. J. Pharm. Biopharm. 2011; 78:27-35.
Mura S, Manconi M, Sinico C, Valenti D, Fadda AM. Penetration enhancer containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil. Int. J. Pharm. 2009; 380:72-79.
Sweetman SC. Martindale: The Complete Drug Reference. 37th ed. London: Pharmaceutical Press; Vol. 1. 2011. p. 417.
Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int. J. Pharm. 2001; 228:43-52.
Patel KK, Kumar P, Thakkar HP. Formulation of niosomal gel for enhanced transdermal lopinavir delivery and its comparative evaluation with ethosomal gel. AAPS Pharm. Sci. Tech. 2012; 13:1502-1510.
Kallinteri P, Antimisiaris S, Karnabatidis D, Kalogeropoulou C, Tsota I, Siablis D. Dexamethasone incorporating liposomes: an in vitro study of their applicability as a slow releasing delivery system of dexamethasone from covered metallic stents. Biomaterials. 2002; 23:4819-4826.
Manosroi A, Kongkaneramit L, Manosroi J. Stability and transdermal absorption of topical amphotericin B liposome formulations. Int. J. Pharm. 2004; 270:279-286.
Fang JY, Hong CT, Chiu WT, Wang YY. Effect of liposomes and niosomes on skin permeation of enoxacin. Int. J. Pharm. 2001; 219:61-72.
Ruckmani K, Jayakar B, Ghosal SK. Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukemia: encapsulation, storage and in vitro release. Drug Dev.Ind.Pharm. 2000; 26:217-222.
Jain RL, Shastri JP. Study of ocular drug delivery system using drug-loaded liposomes. Int. J. Pharm. Investig. 2011; 1: 35-41.
Ramana M, Chaudhari A, Himaja M, Satyanarayana D, Dua K. An approach to minimize pseudomembranous colitis caused by clindamycin through liposomal formulation. Indian J. Pharm.Sci. 2007; 69:390-393.
Zheng-hong W, Qi-neng P, Yi W, Jia-ming L. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. Acta Pharmacol. Sin. 2004; 25:966-972.
El-Gazayerly ON, Hikal AH. Preparation and evaluation of acetazolamide liposomes as an ocular delivery system. Int. J. Pharm. 1997; 158:121-127.
Junyaprasert VB, Manwiwattanakul G. Release profile comparison and stability of diltiazem-resin microcapsules in sustained release suspensions. Int. J. Pharm. 2008; 352:81-91.
El-Samaligy M, Afifi N, Mahmoud E. Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int. J. Pharm. 2006; 308:140-148.
Khan KA. The concept of dissolution efficiency. J. Pharmacol. 1975; 27:98-99.
Ammar HO, Ghorab M, El-Nahhas SA, Higazy IM. Proniosomes as a carrier system for transdermal delivery of tenoxicam. Int. J. Pharm. 2011; 405:142-152.
Shah S, Rahul J, Prabhakar P. Formulation and evaluation of transdermal patches of papaverine hydrochloride. Asian J. Pharm. 2010; 4:79-86.
Mandawgade SD, Patravale VB. Development of SLNs from natural lipids: application to topical delivery of tretinoin. Int. J. Pharm. 2008; 363:132-138.
Uchegbu IF, Vyas SP. Nonionic surfactant based vesicles (niosomes) in drug delivery. Int. J. Pharm. 1998;172: 33-70.
Balakrishnan P , Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, Kim DD, Kim JS, Yoo BK, Choi HG, Woo JS, Yong CS. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int. J. Pharm. 2009; 377:1-8.
Fang SC, Pei Y. Stealth PEG-PHDCA niosomes: effects of chain length of PEG and particle size on rehab surface properties, in vitro drug release, phagocytic uptake, in vivo pharmacokinetics and antitumor activity. J. Pharm. Sci. 2006; 95:1873-1887.
Hao Y, Zhao F, Li N, Yang Y, Li K. Studies on a high encapsulation of colchicine by a niosome system. Int. J. Pharm. 2002; 224:73-80.
RajaNaresh RA, Pillai GK, Udupa N, Chandrashekar G. Anti-inflammatory activity of niosome encapsulated diclofenac sodium in arthritic rats. Indian. J. Pharmacol. 1994; 26:46-48.
Ruckmani K, Sankar V. Formulation and optimization of zidovudine niosomes. AAPS Pharm. Sci. Tech. 2010; 11:1119-1127.
Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20 40 60 and 80) and a sorbitan trimester (Span 85). Int. J. Pharm. 1994; 105:1-6.
Kibbe AH, editor. Handbook of Pharmaceutical Excepients, 3rd ed. American Pharmaceutical Association, Washington, DC, 2000. p. 511-514.
Azeem A, Anwer MK, Talegaonkar S. Niosomes in sustained and targeted drug delivery: some recent advances. J. Drug Target. 2009; 17:671-689.
Hao YM, Li K. Entrapment and release difference resulting from hydrogen bonding interactions in niosomes. Int. J. Pharm. 2011; 403:245-253.
Bayindir ZS, Yuksel N. Characterization of niosomes prepared with various non ionic surfactants for paclitaxel oral delivery. J. Pharm. Sci. 2010; 99:2049-2060.
Nasr M, Mansour S, Mortada ND, Elshamy AA. Vesicular aceclofenac systems: a comparative study between liposomes and niosomes. J. Microencapsul. 2008; 25:499-512.
Devaraj GN, Parakh SR, Devraj R, Apte SS, Rao BR, Rambhau D. Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol. J. Colloid Interface Sci. 2002; 251:360-365.
Liu T, Guo R, Hua W, Qui J. Structure behaviors of hemoglobin in PEG6000/Tween80/Span80/H2O niosome system. Colloids Surf. A: Physicochem. Eng. Aspects. 2007; 293:255-61.
Duxbury MS, Whang EE. RNA interference: a practical approach. J. Surg. Res. 2004; 117:339-344.
Blazek-Welsh AI, Rhodes DG. Maltodextrin-based proniosomes. AAPS Pharm. Sci. 2001; 3:1-8.
Muzzalupo R, Trombino S, Iemma F, Puoci F, La Mesa C, Picci N. Preparation and characterization of bolaform surfactant vesicles. Colloids Surf. B: Biointerfaces. 2005; 46:78-83.
Rania MH, Samar M, Nahed DM, Ahmed SG. Liposomes as an ocular delivery system for acetazolamide: in vitro and in vivo studies. AAPS Pharm. Sci. Tech. 2007; 8:1-12.
Hathout RM, Mansour S, Mortada ND, Guinedi A S. Liposomes as an Ocular Delivery System for Acetazolamide: In Vitro and In Vivo Studies. AAPS Pharm. Sci. Tech. 2007; 8 Suppl 1, Article 1.
Manosroi A, Wongtrakul P, Manosroi J, Sakai H, Sugawara F, Yuasa M, Abe M. Characterization of vesicles prepared with various non ionic surfactants mixed with cholesterol. Colloids Surf. B: Biointerfaces. 2003; 30:129-138.
Hosny KM. Ciprofloxacin as ocular liposomal hydrogel. AAPS Pharm.Sci.Tech. 2010; 11:241-246.
Nagarsenker MS, Londhea VY, Nadkarnib GD. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery. Int. J. Pharm. 1999; 190 Suppl 1:63-71.
Nagarsenker MS, Joshi AA. Preparation, characterization and evaluation of liposomal dispersions of lidocaine, Drug Dev. Ind. Pharmacy. 1997; 23 Suppl 12:1159-1165.
Cocera M, Lopez O, Coderch L, Parra JL, de la Maza A. Permeability investigations of phospholipids liposomes by adding cholesterol. Colloids Surf. A: Physicochem. Eng. Aspects. 2003; 221:9-17.
Abdelbary G., El-gendy N. Niosome-Encapsulated Gentamicin for Ophthalmic Controlled Delivery, AAPS Pharm. Sci. Tech. 2008; 9 Suppl 3: 740-747.
RamaRao K. Microencapsulation of zidovudine by double emulsion solvent diffusion technique using ethyl cellulose. Indian J. Pharm. Sci. 2007; 69:244-250.
Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008; 49:1993-2007.