DONEPEZIL HYDROCHLORIDE LOADED SOLID LIPID NANOPARTICLES: FORMULATION, IN VITRO–IN VIVO PHARMACOKINETIC AND PHARMACODYNAMICS EVALUATION

REKHA DEVI A.; VIDYAVATHI M.

doi:10.22159/ijap.2022v14i3.44145

Authors

REKHA DEVI A. Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati, 517502, India https://orcid.org/0000-0001-8348-4351
VIDYAVATHI M. Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati, 517502, India https://orcid.org/0000-0001-6089-3080

DOI:

https://doi.org/10.22159/ijap.2022v14i3.44145

Keywords:

Solid Lipid Nanoparticle, Optimization, Donepezil HCl, Particle size, Entrapment efficiency

Abstract

Objective: The aim of the present study was to design and in vitro–in vivo evaluation of Donepezil Hydrochloride solid lipid nanoparticles (DHSLN).

Methods: A modified solvent injection method was used to produce Donepezil-loaded solid lipid nanoparticles. A Response Surface Method 3-factor, 2-level Box-Behnken design was applied to study the effect of independent variables on dependent variables. Then it was coated with tween 80 for ease of permeability through the blood-brain barrier due to intact absorption of solid lipid nanoparticles. The prepared SLN was evaluated for particle size, zeta potential analysis, Entrapment efficiency, In vitro drug release study, Field Emission-scanning electron microscopy, In vivo Pharmacokinetic and Pharmacodynamics studies.

Results: The results of coated optimized formulation showed an average particle size of 185.8 nm, entrapment efficiency of 78.52±2.54%, and in vitro drug release of 98.62±3.14% at 36h at pH 7.4. The pharmacokinetic data show higher C_max and improved bioavailability, which was also supported by behavioural changes observed in locomotor activity for surface-modified SLN formulation.

Conclusion: Thus, the current study successfully designed, developed an optimized SLN formulation. The surface-modified SLN proved to enhance the permeability of the drug through barrier, which led to the enhancement of Donepezil bioavailability and locomotor activity.

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References

Garces A, Amaral MH, Sousa Lobo JM, Silva AC. Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cutaneous use: a review. Eur J Pharm Sci. 2018;112:159-67. doi: 10.1016/j.ejps.2017.11.023, PMID 29183800.

Lopez Garcia R, Solid Ganem Ronder V. Lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): occlusive effect and penetration enhancement ability. J Cosmet Dermatol Sci Appl. 2015;5:62-72.

Goo Yoon Park W, In Soo Yoon. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Recent Advances in Drug Delivery. 2013;43:353-62.

Brito Raj S, Chandra Sekhar KB, Bhaskar Reddy K. Formulation, optimization and in vitro evaluation of lipid nanoparticles containing anti-hypertensive drug. Int J Res Pharm Sci. 2015;6:127-30.

Sahu MK, Soni GC, Prajapati SK. Nanostructured lipid carrier: the second generation of solid lipid nanoparticle. Int J Pharm Res Scholars. 2012;1:226-35.

Souto EB, Wissing SA, Barbosa CM, Muller RH. Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. Eur J Pharm Biopharm. 2004;58(1):83-90. doi: 10.1016/j.ejpb.2004.02.015, PMID 15207541.

Bruton Laurence, Parker Keith, Blumenthal Donald. Lain buxton, goodman and gilman’s manual of pharmacology and therapeutics; 2008.

Offermanns Stefan, Rosenthal Walter. Encyclopedia of molecular pharmacology. 2nd ed; 2008.

Garud Akanksha, Singh Deepti, Garud Navneet. Solid lipid nanoparticles (SLN): method, characterization and applications. Int Curr Pharm J. 2012;1(11):384-93. doi: 10.3329/icpj.v1i11.12065.

British Pharmacopoeia. Volume I and II. 7th ed; 2009. p. 1083-6, 5397-401.

Pharmaceutical manufacturing Encyclopedia. 3rd ed; 2 and 4(873-876):040-3042.

Uner Melike, Karaman Ecem Fatma, Aydogmuş Zeynep. Solid lipid nanoparticles and nanostructured lipid carriers of loratadine for topical application: physicochemical stability and drug penetration through rat skin. Trop J Pharm Res. 2014;13(5):653-60. doi: 10.4314/tjpr.v13i5.1.

Fang Jia You, Fang Chia Lang, Liu Chi Hsien, Su Yu Han. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm. 2008;70(2):633-40. doi: 10.1016/j.ejpb.2008.05.008, PMID 18577447.

Bhaskar Kesavan, Krishna Mohan Chinnala Krishna, Lingam Meka, Jagan Mohan Somagoni, Venkateswarlu Vobalaboina, Madhusudan Rao Yamsani, Bhaskar Kesavan, Anbu Jayaraman, Ravichandran Velayudam. Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: in vitro and in vivo characteristics. Drug Dev Ind Pharm. 2009;35(1):98-113. doi: 10.1080/03639040802192822, PMID 18665979.

Gonullu Umit, Uner Melike, Yener Gulgun, Karaman Ecem Fatma, Aydogmuş Zeynep. Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery. Acta Pharm. 2015;65(1):1-13. doi: 10.1515/acph-2015-0009, PMID 25781700.

Bhaskar Reddy K, Jyostna M, Audinarayana N, Madhavi Latha C, Mohanambal E. The enhancement effect of surfactants on the penetration of nitrendipine through rat skin. Indian J Nov Drug Deliv. 2012;4:38-42.

Muller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54Suppl 1:S131-55. doi: 10.1016/s0169-409x(02)00118-7, PMID 12460720.

Ravi Punna Rao, Aditya N, Kathuria Himanshu, Malekar Srinivas, Vats Rahul. Lipid nanoparticles for oral delivery of raloxifene: optimization, stability, in vivo evaluation and uptake mechanism. Eur J Pharm Biopharm. 2014;87(1):114-24. doi: 10.1016/j.ejpb.2013.12.015, PMID 24378615.

Gupta Vivek Kumar, Karar PK. Optimization of process variables for the preparation of chitosan alginate nanoparticles. Int J Pharm Sci. 2011;3:7880.

Yassin Alaa Eldeen B, Anwer Md Khalid, Mowafy Hammam A, El-Bagory Ibrahim M, Bayomi Mohsen A, Alsarra Ibrahim A. Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci. 2010;7(6):398-408. doi: 10.7150/ijms.7.398, PMID 21103076.

Sharma A, Mehta V, Parashar A, Patrwal R, Malairaman U. Solid lipid nanoparticle: fabricated through nanoprecipitation and their physicochemical characterization. Int J Pharm Pharm Sci. 2016;8(10):144-8. doi: 10.22159/ijpps.2016v8i10.13207.

Mangesh Bhalekar R, Prashant Upadhaya, Ashwini Madgulkar. Solid lipid nanoparticles incorporated transdermal patch for improving the permeation of piroxicam. Asian J Pharm. 2016;10:45-50.

Baek Jong Suep, Cho Cheong Weon. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake. Eur J Pharm Biopharm. 2017;117:132-40. doi: 10.1016/j.ejpb.2017.04.013, PMID 28412471.

Xing R, Mustapha O, Ali T, Rehman M, Zaidi SS, Baseer A, Batool S, Mukhtiar M, Shafique S, Malik M, Sohail S, Ali Z, Zahid F, Zeb A, Shah F, Yousaf A, Din F. Development, characterization, and evaluation of SLN-loaded thermoresponsive hydrogel system of topotecan as biological macromolecule for colorectal delivery. BioMed Res Int. 2021;2021:9968602. doi: 10.1155/2021/9968602, PMID 34285920.

Din Fakhar Ud, Jin Sung Giu, Choi Han Gon. Particle and gel characterization of irinotecan-loaded double-reverse thermosensitive hydrogel. Polymers. 2021;13(4):551. doi: 10.3390/polym13040551, PMID 33668441.

Yu Guo, Ali Zakir, Sajjad Khan Anam, Ullah Kalim, Jamshaid Humzah, Zeb Alam, Imran Muhammad, Sarwar Sadia, Choi Han Gon, Ud Din Fakhar. Preparation, pharmacokinetics, and antitumor potential of miltefosine-loaded nanostructured lipid carriers. Int J Nanomedicine. 2021;16:3255-273. doi: 10.2147/IJN.S299443, PMID 34012260.

Khan Anam Sajjad, Ud Din Fakhar, Ali Zakir, Bibi Maryam, Zahid Fatima, Zeb Alam, Mujeeb-Ur-Rehman, Khan Gul Majid. Development, in vitro and in vivo evaluation of miltefosine loaded nanostructured lipid carriers for the treatment of cutaneous leishmaniasis. Int J Pharm. 2021;593:120109. doi: 10.1016/j.ijpharm.2020.120109.

Ganesan Palanivel, Ramalingam Prakash, Karthivashan Govindarajan, Ko Young Tag, Choi Dong Kug. Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases. Int J Nanomedicine. 2018;13:1569-83. doi: 10.2147/IJN.S155593, PMID 29588585.

Gaspar Diana P, Faria Vasco, Quintas Joao P, Almeida Antonio J. Targeted delivery of lipid nanoparticles by means of surface chemical modification. Curr Org Chem. 2017;21(23):2360-75. doi: 10.2174/1385272820666161031161101.

Veerabhadra Rao G, Radha GV, Krishnaji Rao M, Brito Raj S, Bhaskar Reddy K. Formulation, optimization and in vitro evaluation of lovastatin drug loaded solid lipid nanoparticles. Int J Pharm Res. 2020;12:3721-9.

Goppert Torsten M, Muller Rainer H. Protein adsorption patterns on poloxamer-and poloxamine-stabilized solid lipid nanoparticles (SLN). Eur J Pharm Biopharm. 2005;60(3):361-72. doi: 10.1016/j.ejpb.2005.02.006, PMID 15996577.

Selvaraj Brito R, Sridhar Seshaiah K, Kesavan Bhaskar R, Palagati Sucharitha. Application of statistical tooling techniques for designing of carvedilol nanolipid transferosomes and its dermatopharmacokinetic and pharmacodynamic studies. Pharm Nanotechnol. 2020;8(6):452-70. doi: 10.2174/2211738508666200928164820, PMID 32988361.

Schwarz C, Mehnert W, Lucks JS, Muller RH. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J Control Release. 1994;30(1):83-96. doi: 10.1016/0168-3659(94)90047-7.

Kovacevic AB, Muller RH, Savic SD, Vuleta GM, Keck CM. Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: preparation, characterization and physical stability investigation. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2014;444:15-25. doi: 10.1016/j.colsurfa.2013.12.023.

Qushawy M, Nasr A. Solid lipid nanoparticles (sln) as Nano drug delivery carriers: preparation, characterization and application. Int J Appl Pharm. 2020;12:1-9.

Maaben S, Schwarz C, Mehnert W, Lucks JS, Yunis Specht F, Muller BW. Comparison of cytotoxicity between polyester nanoparticles and solid lipid nanoparticles (SLN). Proceedings of the International Symposium Control Rel Bioact Mater. 1993;20:490-1.

Muller RH, Maassen S, Weyhers H, Mehnert W. Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J Drug Target. 1996;4(3):161-70. doi: 10.3109/10611869609015973, PMID 8959488.