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Drug Delivery Letters

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ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

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Research Article

Formulation, Optimization, and In vitro Characterization of Cilnidipineloaded Self-emulsifying Drug Delivery System

Author(s): Renu Kadian and Arun Nanda*

Volume 13, Issue 3, 2023

Published on: 30 May, 2023

Page: [225 - 242] Pages: 18

DOI: 10.2174/2210303113666230502104226

Price: $65

Abstract

Aim: The goal of this research was to formulate and optimize a cost-effective selfemulsifying drug delivery system (SEDDS) of cilnidipine to increase its dissolution rate. Cilnidipine is a BCS class II active pharmaceutical ingredient, which limits its use.

Methods: Cilnidipine's solubility in various oils, surfactants, and cosurfactants, has been investigated. To determine if there is any interaction between cilnidipine and certain excipients, drug compatibility tests were carried out. Based on phase solubility and compatibility studies, two combinations (Canola oil, Tween 80, and PEG 300; Peanut oil, Cremophor EL, and PEG 200) were prepared to create ternary phase diagrams for selecting the best combination with higher microemulsion region and to identify the range of concentration of excipients. Cilnidipine-loaded-SEDDS formulation was prepared by incorporating Canola oil, Tween 80, and PEG 300. For achieving the best formulation, D-optimal mixture design was used. The optimized SEDDS formulation was evaluated for globule size, zeta potential, drug release, drug content, self-emulsification time, and stability studies.

Results: The zeta potential (Y1) and globule size (Y2) of the optimized SEDDS formulation were found to be -36mV and 124.3nm, respectively. The optimized SEDDS formulation showed more than 98% drug release within 15 min in 10% ethanolic 0.1N HCl media, which was significantly higher than that of the pure drug (7.5%) and marketed tablet (~21%). The optimized formulation's self-emulsification time, drug content, and cloud point were 55s, 99.97 ± 1.57 %, and 75.6℃, respectively. After stability studies, there was no evidence of phase separation, colour change, and change in globule size.

Conclusion: A significant improvement in in vitro drug release was observed from cilnidipineloaded- SEDDS.

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[1]
Staessen, J.A.; Wang, J.; Bianchi, G.; Birkenhäger, W.H. Essential hypertension. Lancet, 2003, 361(9369), 1629-1641.
[http://dx.doi.org/10.1016/S0140-6736(03)13302-8] [PMID: 12747893]
[2]
Giles, T.D.; Materson, B.J.; Cohn, J.N.; Kostis, J.B. Definition and classification of hypertension: An update. J. Clin. Hypertens., 2009, 11(11), 611-614.
[http://dx.doi.org/10.1111/j.1751-7176.2009.00179.x] [PMID: 19878368]
[3]
Head, G.A.; Mihailidou, A.S.; Duggan, K.A.; Beilin, L.J.; Berry, N.; Brown, M.A.; Bune, A.J.; Cowley, D.; Chalmers, J.P.; Howe, P.R.C.; Hodgson, J.; Ludbrook, J.; Mangoni, A.A.; McGrath, B.P.; Nelson, M.R.; Sharman, J.E.; Stowasser, M. Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: Prospective cohort study. BMJ, 2010, 340, c1104.
[http://dx.doi.org/10.1136/bmj.c1104] [PMID: 20392760]
[4]
Takahara, A. Cilnidipine: A new generation Ca channel blocker with inhibitory action on sympathetic neurotransmitter release. Cardiovasc. Ther., 2009, 27(2), 124-139.
[http://dx.doi.org/10.1111/j.1755-5922.2009.00079.x] [PMID: 19426250]
[5]
Uneyama, H.; Takahara, A.; Dohmoto, H.; Yoshimoto, R.; Inoue, K.; Akaike, N. Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones. Br. J. Pharmacol., 1997, 122(1), 37-42.
[http://dx.doi.org/10.1038/sj.bjp.0701342] [PMID: 9298526]
[6]
Uneyama, H.; Uchida, H.; Konda, T.; Yoshimoto, R. Cilnidipine: Preclinical profile and clinical evaluation. Cardiovasc. Drug Rev., 1999, 17(4), 341-357.
[http://dx.doi.org/10.1111/j.1527-3466.1999.tb00024.x]
[7]
Cilnidipine, Drug bank Available From: https://go.drugbank.com/drugs/DB09232
[8]
Kohli, K.; Chopra, S.; Dhar, D.; Arora, S.; Khar, R.K. Self-emulsifying drug delivery systems: An approach to enhance oral bioavailability. Drug Discov. Today, 2010, 15(21-22), 958-965.
[http://dx.doi.org/10.1016/j.drudis.2010.08.007] [PMID: 20727418]
[9]
Shrestha, H.; Bala, R.; Arora, S. Lipid-Based Drug Delivery Systems. J. Pharm., 2014, 2014, 801820.
[http://dx.doi.org/10.1155/2014/801820] [PMID: 26556202]
[10]
Sassene, P.; Kleberg, K.; Williams, H.D.; Bakala-N’Goma, J.C.; Carrière, F.; Calderone, M.; Jannin, V.; Igonin, A.; Partheil, A.; Marchaud, D.; Jule, E.; Vertommen, J.; Maio, M.; Blundell, R.; Benameur, H.; Porter, C.J.H.; Pouton, C.W.; Müllertz, A. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 6: Effects of varying pancreatin and calcium levels. AAPS J., 2014, 16(6), 1344-1357.
[http://dx.doi.org/10.1208/s12248-014-9672-x] [PMID: 25274609]
[11]
Kommuru, T.R.; Gurley, B.; Khan, M.A.; Reddy, I.K. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: Formulation development and bioavailability assessment. Int. J. Pharm., 2001, 212(2), 233-246.
[http://dx.doi.org/10.1016/S0378-5173(00)00614-1] [PMID: 11165081]
[12]
Son, H.Y.; Chae, B.R.; Choi, J.Y.; Shin, D.J.; Goo, Y.T.; Lee, E.S.; Kang, T.H.; Kim, C.H.; Yoon, H.Y.; Choi, Y.W. Optimization of self-microemulsifying drug delivery system for phospholipid complex of telmisartan using D-optimal mixture design. PLoS One, 2018, 13(12), e0208339.
[http://dx.doi.org/10.1371/journal.pone.0208339] [PMID: 30517187]
[13]
Jin, X.; Zhang, Y.; Xiao, L.; Zhao, Z. optimization of extended zero-order release gliclazide tablets using D-optimal mixture design. Yakugaku Zasshi, 2008, 128(10), 1475-1483.
[http://dx.doi.org/10.1248/yakushi.128.1475] [PMID: 18827468]
[14]
Choi, Y.W.; Yeom, D.W.; Song, Y.S.; Kim, S.R.; Lee, S.G.; Kang, M.H.; Lee, S.K. Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design. Int. J. Nanomedi, 2015, 10, 3865-3877.
[http://dx.doi.org/10.2147/IJN.S83520] [PMID: 26089663]
[15]
Subudhi, B.B.; Mandal, S. Self-microemulsifying drug delivery system: formulation and study intestinal permeability of ibuprofen in rats. J. Pharm., 2013, 2013, 328769.
[http://dx.doi.org/10.1155/2013/328769] [PMID: 26555973]
[16]
Cui, S.; Nie, S.; Li, L.; Wang, C.; Pan, W.; Sun, J. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine. Drug Dev. Ind. Pharm., 2009, 35(5), 603-611.
[http://dx.doi.org/10.1080/03639040802488089] [PMID: 19040178]
[17]
Parmar, N.; Singla, N.; Amin, S.; Kohli, K. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. Colloids Surf. B Biointerfaces, 2011, 86(2), 327-338.
[http://dx.doi.org/10.1016/j.colsurfb.2011.04.016] [PMID: 21550214]
[18]
Mura, P.; Furlanetto, S.; Cirri, M.; Maestrelli, F.; Marras, A.M.; Pinzauti, S. Optimization of glibenclamide tablet composition through the combined use of differential scanning calorimetry and d-optimal mixture experimental design. J. Pharm. Biomed. Anal., 2005, 37(1), 65-71.
[http://dx.doi.org/10.1016/j.jpba.2004.09.047] [PMID: 15664744]
[19]
Singh, B.; Khurana, L.; Bandyopadhyay, S.; Kapil, R.; Katare, O.O.P. Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential. Drug Deliv., 2011, 18(8), 599-612.
[http://dx.doi.org/10.3109/10717544.2011.604686] [PMID: 22008038]
[20]
Agrawal, A.G.; Kumar, A.; Gide, P.S. Self emulsifying drug delivery system for enhanced solubility and dissolution of glipizide. Colloids Surf. B Biointerfaces, 2015, 126, 553-560.
[http://dx.doi.org/10.1016/j.colsurfb.2014.11.022] [PMID: 25576032]
[21]
Singh, G.; Pai, R.S. Trans -resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies. Drug Deliv., 2015, 22(4), 522-530.
[http://dx.doi.org/10.3109/10717544.2014.885616] [PMID: 24512464]
[22]
Chintalapudi, R.; Murthy, T.E.G.K.; Lakshmi, K.R.; Manohar, G.G. Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine. Int. J. Pharm. Investig., 2015, 5(4), 205-213.
[http://dx.doi.org/10.4103/2230-973X.167676] [PMID: 26682191]
[23]
Liu, Q.; Mai, Y.; Gu, X.; Zhao, Y.; Di, X.; Ma, X.; Yang, J. A wet-milling method for the preparation of cilnidipine nanosuspension with enhanced dissolution and oral bioavailability. J. Drug Deliv. Sci. Technol., 2020, 55, 101371.
[http://dx.doi.org/10.1016/j.jddst.2019.101371]
[24]
Martin, A.; Bustamante, P. Physical Pharmacy; Waverly International: Maryland, USA, 1993.
[25]
Aukema, H.; Campbell, L. Oil nutrition and utilization.Canola chemistry, production, processing and utilization; Daun, J.K.; Eskin, M.N.A; Hickling, D., Ed.; AOCS Press: USA, 2011, pp. 245-280.
[26]
Arya, S.S.; Salve, A.R.; Chauhan, S. Peanuts as functional food: A review. J. Food Sci. Technol., 2016, 53(1), 31-41.
[http://dx.doi.org/10.1007/s13197-015-2007-9] [PMID: 26787930]
[27]
Patel, A.R.; Vavia, P.R. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate. AAPS J., 2007, 9(3), E344-E352.
[http://dx.doi.org/10.1208/aapsj0903041] [PMID: 18170981]
[28]
StatEase®, Design-Expert® software version 13. Available From: https://www.statease.com/ [Accessed on: 27th Feb 2022].
[29]
Balakrishnan, P.; Lee, B.J.; Oh, D.H.; Kim, J.O.; Lee, Y.I.; Kim, D.D.; Jee, J.P.; Lee, Y.B.; Woo, J.S.; Yong, C.S.; Choi, H.G. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int. J. Pharm., 2009, 374(1-2), 66-72.
[http://dx.doi.org/10.1016/j.ijpharm.2009.03.008] [PMID: 19446761]
[30]
Amdoun, R.; Khelifi, L.; Khelifi-Slaoui, M.; Amroune, S.; Asch, M.; Assaf-ducrocq, C.; Gontier, E. The desirability optimization methodology; A tool to predict two antagonist responses in biotechnological systems: Case of biomass growth and hyoscyamine content in elicited Datura starmonium hairy roots. Iran. J. Biotechnol., 2018, 16(1), 11-19.
[http://dx.doi.org/10.21859/ijb.1339] [PMID: 30555836]
[31]
Bakhle, S.S.; Avari, J.G. Development and characterization of solid self-emulsifying Drug delivery system of cilnidipine. Chem. Pharm. Bull., 2015, 63(6), 408-417.
[http://dx.doi.org/10.1248/cpb.c14-00326] [PMID: 26027464]
[32]
Balakumar, K.; Raghavan, C.V. selvan, N.T.; prasad, R.H.; Abdu, S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf. B Biointerfaces, 2013, 112, 337-343.
[http://dx.doi.org/10.1016/j.colsurfb.2013.08.025] [PMID: 24012665]
[33]
Kallakunta, V.R.; Eedara, B.B.; Jukanti, R.; Ajmeera, R.K.; Bandari, S. A Gelucire 44/14 and labrasol based solid self emulsifying drug delivery system: Formulation and evaluation. J. Pharm. Investig., 2013, 43(3), 185-196.
[http://dx.doi.org/10.1007/s40005-013-0060-9]
[34]
Shah, V.P.; Tsong, Y.; Sathe, P.; Williams, R.L. Dissolution profile comparison using similarity factor, f2. Dissolut. Technol., 1999, 6(3), 15-15.
[http://dx.doi.org/10.14227/DT060399P15]
[35]
Guidance for industry. Dissolution testing of immediate release solid oral dosage forms, U.S. department of health and human services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 1997. Available From: https://www.fda.gov/media/70936/download#:~:text=The%20BCS%20suggests%20that%20for,is%20not%20limited%20by%20dissolution [Accessed on: 1st March 2022].
[36]
Kadu, P.J.; Kushare, S.S.; Thacker, D.D.; Gattani, S.G. Enhancement of oral bioavailability of atorvastatin calcium by self-emulsifying drug delivery systems (SEDDS). Pharm. Dev. Technol., 2011, 16(1), 65-74.
[http://dx.doi.org/10.3109/10837450903499333] [PMID: 20088679]
[37]
Balakrishnan, P.; Lee, B.J.; Oh, D.H.; Kim, J.O.; Hong, M.J.; Jee, J.P.; Kim, J.A.; Yoo, B.K.; Woo, J.S.; Yong, C.S.; Choi, H.G. Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS). Eur. J. Pharm. Biopharm., 2009, 72(3), 539-545.
[http://dx.doi.org/10.1016/j.ejpb.2009.03.001] [PMID: 19298857]

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