Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach

Sundaresan Nandhini , Kaliappan Ilango

Abstract


Background and purpose: Vasicine is a potential bronchodilator and can be used for the effective management of asthma and bronchitis. It has low absorption in the gastrointestinal tract due to its poor solubility thereby low bioavailability. The objective of this research was to develop a novel drug delivery system of vasaka extract to improve its bioavailability by enhancing the solubility and absorption of vasicine.

Experimental approach: Vasaka-loaded phytosomes were developed and optimized by thin-layer hydration technique using systematic quality by design approach. Box-Behnken design (32 factorial design) using Design-Expert software was employed to optimize phytosome wherein phosphatidylcholine concentration (X1), stirring temperature (X2), and stirring time (X3) were selected as independent variables. Yield (%), particle size (nm), and entrapment efficiency (%) were evaluated as responses. The optimized phytosome was characterized by studying the surface morphology such as FE-SEM and TEM analysis, thermal characteristics by thermal gravimetric analysis and spectral and diffraction studies by FTIR and XRD analysis and studying the dissolution behaviour of phytosome by in vitro release study.

Findings/Results: The percentage yield, particle size, and entrapment efficiency values of the phytosomes were found in the range of 30.03-97.03%, 231.0-701.4 nm, and 20.02-95.88% w/w, respectively. The optimized phytosome showed the zeta potential of -23.2 mV exhibited good stability and SEM and TEM analysis revealed the spherical shape and smooth particles with the uniform particle size distribution of phytosomes. The comparative in vitro drug release study of vasaka extract and phytosome revealed the sustained release characteristics of phytosome which reached 68.80% at 8 h compared to vasaka extract reached a maximum of 45.08% at 4 h.

Conclusion and implication: The results highlighted the importance of optimization of formulation development using quality by design strategy to achieve consistent quality of pharmaceutical products.

 

 


Keywords


Adhatoda vasica; Box Behnken design; Phosphatidylcholine; Phytosome; Vasicine.

Full Text:

PDF

References


Alkhamaiseh SI, Aljofan M. Prevalence of use and reported side effects of herbal medicine among adults in Saudi Arabia. Complement Ther Med. 2020;48:102255,1-6.

DOI: 10.1016/j.ctim.2019.102255.

Flores IS, Martinelli BC, Liao LM. High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) as a tool in the determination of biomarkers of Passiflora-based herbal medicines. Fitoterapia. 2020;142:104500,1-6.

DOI: 10.1016/j.fitote.2020.104500.

Yang K, Long XM, Cao JJ, Li YJ, Wu Y, Bai X, et al. An analytical strategy to explore the multicomponent pharmacokinetics of herbal medicine independently of standards: application in Gelsemium elegans extracts. J Pharm Biomed Anal. 2019;176:112833,1-13.

DOI: 10.1016/j.jpba.2019.112833.

Herbal medicine market research report-global forecast till 2023. July, 2019. Available from: https://www.marketresearchfuture.com/reports/herbal-medicine-market-3250.

Harwansh RK, Deshmukh R, Rahman MA. Nanoemulsion: Promising nanocarrier system for delivery of herbal bioactives. J Drug Deliv Sci Tec. 2019;51:224-233.

DOI: 10.1016/j.jddst.2019.03.006.

Kuncahyo I, Choiri S, Fudholi A, Rohman A, Martien R. Understanding the effect of lipid formulation loading and ethanol as a diluent on solidification of pitavastatin super-saturable SNEDDS using factorial design approach. Res Pharm Sci. 2019;14(5):378-390.

DOI: 10.4103/1735-5362.268198.

Ajazuddin, Saraf S. Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010;81(7):680-689.

DOI: 10.1016/j.fitote.2010.05.001.

Namdari M, Eatemadi A, Soleimaninejad M, Hammed AT. A brief review on the application of nanoparticle enclosed herbal medicine for the treatment of infective endocarditis. Biomed Pharmacother. 2017;87:321-331.

DOI: 10.1016/j.biopha.2016.12.099.

Kashyap S, Singh A, Mishra A, Singh V. Enhanced sustained release of furosemide in long circulating chitosan-conjugated PLGA nanoparticles. Res Pharm Sci. 2019;14(2):93-106.

DOI: 10.4103/1735-5362.253356.

Khogta S, Patel J, Barve K, Londhe V. Herbal nano-formulations for topical delivery. J Herb Med. 2019;20:100300,1-9.

DOI: 10.1016/j.hermed.2019.100300.

Nalini T, Kumari S, Basha K. Novel nanosystems for herbal drug delivery. World J Pharm Pharm Sci. 2017;6(5):1447-1463.

DOI: 10.20959/wjpps201705-9183.

Freag MS, Saleh WM, Abdallah OY. Laminated chitosan-based composite sponges for transmucosal delivery of novel protamine-decorated tripterine phytosomes: ex-vivo mucopenetration and in-vivo pharmacokinetic assessments. Carbohydr Polym. 2018;188:108-120.

DOI: 10.1016/j.carbpol.2018.01.095.

Montes C, Villaseñor MJ, Ríos Á. Analytical control of nanodelivery lipid-based systems for encapsulation of nutraceuticals: achievements and challenges. Trends Food Sci Tech. 2019;90:47-62.

DOI: 10.1016/j.tifs.2019.06.001.

Kapoor B, Gupta R, Gulati M, Singh SK, Khursheed R, Gupta M. The Why, Where, Who, How, and What of the vesicular delivery systems. Adv Colloid Interface Sci. 2019;271:101985,1-18.

DOI: 10.1016/j.cis.2019.07.006.

Silki W, Deepak K, Sarvesh M, Vaibhav T, Prakash KO. Potential and promises of phospholipid structured novel formulations for hepatoprotection. Int J Drug Dev Res. 2012;4(1):51-58.

Singh RP, Gangadharappa HV, Mruthunjaya K. Phospholipids: unique carriers for drug delivery systems. J Drug Deliv Sci Tec. 2017;39:166-179.

DOI: 10.1016/j.jddst.2017.03.027.

Khan MS, Krishnaraj K. Phospholipids: a novel adjuvant in herbal drug delivery systems. Crit Rev Ther Drug Carrier Syst. 2014;31(5):407-428.

DOI: 10.1615/critrevtherdrugcarriersyst.2014010634.

Gurumukhi VC, Bari SB. Fabrication of efavirenz loaded nano-formulation using quality by design (QbD) based approach: exploring characterizations and in vivo safety. J Drug Deliv Sci Tec. 2020;56(A):101545,1-18.

DOI: 10.1016/j.jddst.2020.101545.

Amasya G, Aksu B, Badilli U, Onay-Besikci A, Tarimci N. QbD guided early pharmaceutical development study: production of lipid nanoparticles by high pressure homogenization for skin cancer treatment. Int J Pharm. 2019;563:110-121.

DOI: 10.1016/j.ijpharm.2019.03.056.

Aksu NB, Yozgatlı V, Okur ME, Ayla Ş, Yoltaş A, Okur NÜ. Preparation and evaluation of QbD based fusidic acid loaded in situ gel formulations for burn wound treatment. J Drug Deliv Sci Tec. 2019;52:110-121.

DOI: 10.1016/j.jddst.2019.04.015.

Bonde S, Tambe K. Lectin coupled liposomes for pulmonary delivery of salbutamol sulphate for better management of asthma: formulation development using QbD approach. J Drug Deliv Sci Tec. 2019;54:101336,1-9.

DOI: 10.1016/j.jddst.2019.101336.

Colobatiu L, Gavan A, Mocan A, Bogdan C, Mirel S, Tomuta I. Development of bioactive compounds-loaded chitosan films by using a QbD approach-a novel and potential wound dressing material. React Funct Polym. 2019;138:46-54.

DOI: 10.1016/j.reactfunctpolym.2019.02.013.

Pallagi E, Jójárt-Laczkovich O, Németh Z, Szabó-Révész P, Csóka I. Application of the QbD-based approach in the early development of liposomes for nasal administration. Int J Pharm. 2019;562:11-22.

DOI: 10.1016/j.ijpharm.2019.03.021.

Hasnain MS, Javed MN, Alam MS, Rishishwar P, Rishishwar S, Ali S, et al. Purple heart plant leaves extract-mediated silver nanoparticle synthesis: optimization by Box-Behnken design. Mater Sci Eng C. 2019;99:1105-1114.

DOI: 10.1016/j.msec.2019.02.061.

Jazuli I, Annu, Nabi B, Moolakkadath T, Alam T, Baboota S, et al. Optimization of nanostructured lipid carriers of lurasidone hydrochloride using Box-Behnken design for brain targeting: in vitro and in vivo studies. J Pharm Sci. 2019;108(9):3082-3090.

DOI: 10.1016/j.xphs.2019.05.001.

Hossain MT, Hoq MO. Therapeutic use of Adhatoda vasica. Asian J Med Biol Res. 2016;2(2):156-163.

DOI: 10.3329/ajmbr.v2i2.29005.

Indian drug manufacturers' association, Indian herbal pharmacopoeia, India, Mumbai: India drug manufacturing association; 2002. pp: 33-39.

Singh A, Kumar S, Bajpai V, Kumar B. Simultaneous determination of pyrroquinazoline alkaloids and flavonoids in Adhatoda beddomei and Adhatoda vasica and their marketed herbal formulations using ultra-high-performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometer. Biomed Chromatogr. 2017;31(3):3827,1-22.

DOI: 10.1002/bmc.3827.

Gupta OP, Anand KK, Ghatak BJ, Atal CK. Vasicine, alkaloid of Adhatoda vasica, a promising uterotonic abortifacient. Indian J Exp Biol. 1978;16(10):1075-1077.

Atal CK. Chemistry and pharmacology of vasicine-a new oxytocic and abortifacient. India: Regional research laboratory; 1980. pp: 15-18.

Chakraborty A, Brantner AH. Study of alkaloids from Adhatoda vasica Nees on their anti-inflammatory activity. Phytother Res. 2001;15(6):532-534.

DOI: 10.1002/ptr.737.

Srinivasarao D, Jayarraj IA, Jayarraj R, Prabha ML. A study on antioxidant and anti-inflammatory activity of vasicine against lung damage in rats. Ind J Allergy Asthma Immunol. 2006;20(1):1-7.

Dash RP, Chauhan BF, Anandjiwala S, Nivsarkar M. Comparative pharmacokinetics profile of Vasa Swaras with vasicine and vasicinone. Chromatographia. 2010;71:609-615.

DOI: 10.1365/s10337-010-1517-x.

Singh B, Sharma RA. Pyrroloquinazoline alkaloids from tissue cultures of Adhatoda vasica and their antioxidative activity. Am J Phytomed Clin Therapeut. 2014;2:403-412.

Maryana W, Rachmawati H, Mudhakir D. Formation of phytosome containing silymarin using thin layer-hydration technique aimed for oral delivery. Mater Today: Proceedings. 2016;3(3):855-866.

DOI: 10.1016/j.matpr.2016.02.019.

Arora D, Nanda S. Quality by design driven development of resveratrol loaded ethosomal hydrogel for improved dermatological benefits via enhanced skin permeation and retention. Int J Pharm. 2019;567:118448,1-13.

DOI: 10.1016/j.ijpharm.2019.118448.

Negi P, Singh B, Sharma G, Beg S, Raza K, Katare OP. Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv. 2016;23(3):941-957.

DOI: 10.3109/10717544.2014.923067.

Beg S, Saini S, Bandopadhyay S, Katare OP, Singh B. QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil employing multivariate statistical techniques. Drug Dev Ind Pharm. 2018;44(3):407-420.

DOI: 10.1080/03639045.2017.1395459.

Semalty A, Semalty M, Singh D, Rawat MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem. 2010;67:253-260.

DOI: 10.1007/s10847-009-9705-8.

Semalty A, Semalty M, Singh D, Rawat MSM. Phyto-phospholipid complex of catechin in value added herbal drug delivery. J Incl Phenom Macrocycl Chem. 2012;73:377-386.

DOI: 10.1007/s10847-011-0074-8.

Shaker S, Gardouh AR, Ghorab MM. Factors affecting liposomes particle size prepared by ethanol by ethanol injection method. Res Pharm Sci. 2017;12(5):346-352.

DOI: 10.4103/1735-5362.213979.

Vyas T, Dash RP, Anandjiwala S, Nivsarkar M. Formulation and pharmacokinetic evaluation of hard gelatin capsule encapsulating lyophilized Vasa Swaras for improved stability and oral bioavailability of vasicine. Fitoterapia. 2011;82(3):446-453.

DOI: 10.1016/j.fitote.2010.12.005.

Malik JK, Sharma A, Singh S, Jain S. RETRACTED: nanosuspension of vasicine from Adhatoda vasica: isolation and characterization. Drug Invent Today. 2013;5(1):32-38.

DOI: 10.1016/j.dit.2013.03.005.

Tan Q, Liu S, Chen X, Wu M, Wang H, Yin H, et al. Design and evaluation of a novel evodiamine-phospholipid complex for improved oral bioavailability. AAPS PharmSciTech. 2012;13(2):534-547.

DOI: 10.1208/s12249-012-9772-9.

Dhore PW, Dave VS, Saoji SD, Bobde YS, Mack C, Raut NA. Enhancement of the aqueous solubility and permeability of a poorly water soluble drug ritonavir via lyophilized milk-based solid dispersions. Pharm Dev Technol. 2017;22(1):90-102.

DOI: 10.1080/10837450.2016.1193193.

Freitas C, Müller RH. Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. Int J Pharm. 1998;168(2):221-229.

DOI: 10.1016/S0378-5173(98)00092-1.

Yue PF, Zhang WJ, Yuan HL, Yang M, Zhu WF, Cai PL, et al. Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid–phospholipid complex. AAPS PharmSciTech. 2008;9(1):322-329.

DOI: 10.1208/s12249-008-9040-1.

Perrut M, Jung J, Leboeuf F. Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes: part I: micronization of neat particles. Int J Pharm. 2005;288(1):3-10.

DOI: 10.1016/j.ijpharm.2004.09.007.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.