Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin

Pavan Ram Kamble; Karimunnisa Sameer Shaikh

doi:10.1055/a-1332-2037

Planta Medica, Inhaltsverzeichnis

Planta Med 2022; 88(01): 79-90
DOI: 10.1055/a-1332-2037

Formulation and Delivery Systems of Natural Products

Original Papers

Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin

Pavan Ram Kamble

Progressive Education Societyʼs Modern College of Pharmacy, Yamunanagar, Nigdi, Pune, Maharashtra, India (Affiliated with Savitribai Phule Pune University)

,

Karimunnisa Sameer Shaikh

Progressive Education Societyʼs Modern College of Pharmacy, Yamunanagar, Nigdi, Pune, Maharashtra, India (Affiliated with Savitribai Phule Pune University)

› Institutsangaben

Abstract

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X₁ (oil) and X₂ (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were − 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

Key words

Plumbago zeylanica - Plumbaginaceae - solubility - SNEDDS - bioavailability - plumbagin

Volltext

Referenzen

References
1 Alpana R. Effect of Plumbago zeylanica in hyperlipidaemic rabbits and its modification by vitamin E. Indian J Pharmacology 1996; 28: 161-166
2 Kodati DR, Burra S, Goud PK. Evaluation of wound healing activity of methanolic root extract of Plumbago zeylanica L. in wistar albino rats. Asian J Plant Sci Res 2011; 1: 26-34
3 Christudas S, Veeramuthu D, Paul A, Savarimuthu I. Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats. Food Chem. Toxicol 2012; 50: 4356-4363
4 Vijayakumar R, Senthilvelan M, Ravindran R, Sheela DR. Plumbago zeylanica action on blood coagulation profile with and without blood volume reduction. Vascul Pharmacol 2006; 45: 86-90
5 Dai Y, Hou LF, Chan JP. Inhibition of immediate allergic reactions by ethanol extract from Plumbago zeylanica stems. Biol Pharm Bull 2004; 27: 429-432
6 Bopaiah CP, Pradhan N. Central nervous system stimulatory action from the root extract of Plumbago zeylanica in rats. Phytother Res 2001; 15: 153-156
7 Lin LC, Yang LL, Chou CJ. Cytotoxic naphthoquinones and plumbagic acid glucosides from Plumbago zeylanica . Phytochemistry 2003; 62: 619-622
8 Luo P, Wong YF, Ge L, Zhang ZF, Liu Y, Liu L, Zhou L. Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-κB activation. J Pharmacol Exp Ther 2010; 335: 735-742
9 Jeyachandran R, Mahesh A, Cindrella L, Sudhakar S, Pazhanichamy K. Antibacterial activity of plumbagin and root extracts of Plumbago Zeylanica L. Acta Biol Crac Ser Bot 2009; 51: 17-22
10 Shinde PV, Wadekar MP. Structural, thermal and antifungal activity studies of isomeric Sm(III) Juglonates. Der Pharma Chemica 2015; 7: 231-239
11 Bothiraja C, Pawar AP, Mali AJ, Shaikh KS. Improved pharmaceutical properties of surface modified plumbagin bioactive crystals. Int J Surf Sci Eng 2013; 7: 181-195
12 Singh UV, Udupa N. Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma. Indian J Physiol Pharmacol 1997; 41: 171-175
13 Sheik DSP, Abdulla A, Basuvaraj SK, Jasmespandi A, Kasi P. Synthesis, characterization, and DNA binding studies of nanoplumbagin. J Nanomater 2014;
14 Rajalakshmi S, Pawar AP, Mali AJ, Chellampillai B. Crystal engineering of bioactive plumbagin using anti-solvent precipitation, melt solidification and sonocrystallization techniques. Mater Res Express 2014; 1: 1-19
15 Kumar MR, Aithal BK, Udupa N, Reddy MS, Raakesh V, Murthy RS, Raju DP, Rao BS. Formulation of plumbagin loaded long circulating pegylated liposomes: in vivo evaluation in C57BL/6J mice bearing B16F1 melanoma. Drug Deliv 2011; 18: 511-522
16 Mandala RSK, Aithal K, Anandam A, Shavi G, Nayanabhirama U, Arumugam K. Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamics evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma. Drug Deliv 2010; 17: 103-113
17 Rajendra N, Mohammed H, Touseef H, Devi R. Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution. Saudi Pharm J 2015; 23: 528-540
18 Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv 2015; 22: 552-561
19 Kazi M, Al-Swairi M, Ahmad A, Raish M, Alanazi FK, Badran MM, Khan AA, Alanazi AM, Hussain MD. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: preparation, in vitro and in vivo assessment. Front Pharmacol 2019; 10: 459
20 Kassema AA, Mohsen AM, Ahmed RS, Essam TM. Self-nanoemulsifying drug delivery system (SNEDDS) with enhanced solubilization of nystatin for treatment of oral candidiasis: design, optimization, in vitro and in vivo evaluation. J Mol Liq 2016; 218: 219-232
21 Constantinides PP, Scalart JP, Lancaster C, Marcello J, Marks G, Ellens H, Smith PL. Formulation and intestinal absorption enhancement evaluation of water in-oil microemulsions incorporating medium-chain glycerides. Pharm Res 1994; 11: 1385-1390
22 Baloch J, Sohail MF, Sarwar HS, Kiani MS, Khan GM, Jahan S, Rafay M, Chaudhry MT, Yasinzai M, Shahnaz G. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: in vitro and in vivo evaluation. Medicina 2019; 55: 210
23 Tonga Y, Zhangb Q, Shib W, Wanga J. Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS. Drug Deliv 2019; 26: 1155-1166
24 Sakloetsakuna D, Dünnhauptb S, Barthelmesb J, Pererab G, Bernkop-Schnürchb A. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration. Int J Biol Macromol 2013; 61: 363-372
25 Inugala S, Eedara BB, Sunkavalli S, Dhurke R, Kandadi P, Jukanti R, Bandari S. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: in vitro and in vivo evaluation. Eur J Pharm Sci 2015; 74: 1-10
26 Kamble PR, Shaikh KS. Effect of surfactants and cosurfactants on phase behaviour and physicochemical properties of self-nanoemulsifying drug delivery system loaded with plumbagin. Indo Global J Pharm Sci 2020; 10: 1-11
27 El-Assal MI, El-Gendy MA, Tadros MI, El-Gazayerly ON. Olmesartan medoxomil-loaded self-nanoemulsifying drug delivery systems: design, in vitro characterization, and pharmacokinetic assessments in rabbits via LC-Ms/Ms. IJPSR 2018; 9: 945-955
28 Kamisetti RR, Gupta RM. Solubility enhancement of ebastine by self–nanoemulsifying delivery strategy formulation, optimization and characterization. Int J Pharm Sci Nanotech 2017; 10 (04) 3779-3787
29 Talele S, Derle D. Solubility and thermodynamic modeling of quetiapine fumarate in self-nanoemulsifying drug delivery system (SNEDDS). Int J App Pharm 2018; 10: 127-132
30 Kamble PR, Shaikh KS, Chaudhari PD. Application of liquisolid technology for enhancing solubility and dissolution of rosuvastatin. Adv Pharm Bull 2014; 4: 197-204
31 Lia F, Rongfeng H, Bin W, Yun G, Gang C, Song G, Lei Y, Jihui T. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake. Acta Pharm Sin B 2017; 7: 353-360
32 Imada C, Takahashi T, Kuramoto M, Masuda K, Ogawara K, Sato A, Wataya Y, Kim H, Higaki K. Improvement of oral bioavailability of N-251, a novel antimalarial drug, by increasing lymphatic transport with long-chain fatty acid-based self-nanoemulsifying drug delivery system. Pharm Res 2015; 32: 2595-2608
33 Valicherla GR, Dave KM, Syed AA, Riyazuddin M, Gupta AP, Singh A, Wahajuddin. Mitra K, Datta D, Jiaur R, Gayen JR. Formulation optimization of docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity. Sci Rep 2016; 6: 26895
34 Patel G, Shelat P, Lalwani A. Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment. Drug Deliv 2016; 23: 3027-3042
35 Hyma P, Chandra A, Abbulu K. Formulation and characterization of telmisartan self-microemulsifying drug delivery system. Int J Pharm Phar Sci 2014; 6: 6120-6125
36 Balakumar K, Raghavan CV, Selvan NT, Prasad RH, 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
37 Chintalapudi R, Murthy T, Lakshmi KR, Manohar GG. Formulation, optimization, and evaluation of self emulsifying drug delivery systems of nevirapine. Int J Pharma Investig 2015; 5: 205-213
38 Beg S, Sandhu PS, Batra RS, Khurana RK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Deliv 2015; 22: 765-784
39 Singh D, Bedi N. Canagliflozin loaded SMEDDS: formulation optimization for improved solubility, permeability and pharmacokinetic performance. Int J Pharm Investig 2018; 49: 67-85
40 Tahnee JD, Shasha R, Thomas N, Clive AP. Novel nanostructured solid materials for modulating oral drug delivery from solid-state lipid-based drug delivery systems. AAPS J 2016; 18: 23-40
41 Jaimeen P, Gordhan C, Shruti D, Ankini P, Chhagan P. Self-nanoemulsifying powder of isotretinoin: preparation and characterization. J Powder Technol 2013;
42 Hsieh YJ, Lin LC, Tsai TH. Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2006; 844: 1-5
43 Yamaoka K, Nakagawa T, Uno T. Application of Akaikeʼs information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978; 6: 165-175
44 Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX. Prediction of human absorption on natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem 2006; 4: 605-610
45 Sharma P, Chawla HP, Panchagnula R. LC determination of cephalosporins in in-vitro rat intestinal sac absorption model. J Pharm Biomed Anal 2002; 27: 39-50

Zusatzmaterial

Supporting Information