Donepezil Base: Physicochemical Characterization, HPLC Method Development, Validation and its Application for the Determination of Shelf Life in Developed Solid Lipid Nanoparticles

Author(s): Mohd Yasir*, Udai V. Singh Sara, Iti Chauhan, Dheeraj Bisht, Dinesh Puri, Jayendra Maurya

Journal Name: Current Nanomedicine
Formerly Recent Patents on Nanomedicine

Volume 10 , Issue 1 , 2020

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Abstract:

Background/Objectives: Donepezil (DPL) is available as the hydrochloride salt (DPL-HCL) which is highly water-soluble, prompting leakage of the drug into water phase during solid lipid nanoparticles (SLNs) preparation which leads to reduce the entrapment efficiency as well as drug content. So, the drug was converted into its base form i.e. donepezil base (DPL base). The main objective of the work was to study the physicochemical characterization and identification of DPL base and to compare it with parent DPL-HCL, to develop a High-Performance Liquid Chromatography (HPLC) method for the detection of DPL base in SLNs. The develop method was used for the determination of shelf life of drug in SLNs.

Methods: DPL-HCL was converted into DPL base simply by alkalization of DPL- HCL with NaOH and then extracted into dichloromethane (DCM) followed by drying to obtain DPL base. The HPLC method was developed and validated to quantify the DPL base for the determination of its shelf life in SLNs. The drug content in the developed SLNs was determined by extracting the DPL base using methanol as a solvent. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ).

Results: DPL-HCL was successfully converted into DPL base with a yield value of 88.61%. The optimized mobile phase was comprised of 0.02 M phosphate buffer (pH 7.4), methanol and Acetonitrile (ACN) (40:50:10 v/v/v). The pH of mobile phase was adjusted with o-phosphoric acid. The linearity range of the developed method was found to be 0.5-80 µg/mL with LOD and LOQ value 0.086 and 0.263 µg/ml respectively. The shelf life of the DPL base in SLNs was found to be 2.29 years.

Conclusion: The HPLC method for donepezil base was successfully developed and validated. RSD values for validated parameters were < 2, indicating the authenticity of the developed method. The method was successfully used for the determination of shelf life of the drug in SLNs.

Keywords: Donepezil, high-performance liquid chromatography, shelf life, solid lipid nanoparticles, validation, hydrochloride salt (DPL-HCL).

[1]
Zhang P, Chen L, Gu W, Xu Z, Gao Y, Li Y. In vitro and in vivo evaluation of donepezil-sustained release microparticles for the treatment of Alzheimer’s disease. Biomaterials 2007; 28(10): 1882-8.
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.016] [PMID: 17196249]
[2]
McShane R, Westby MJ, Roberts E, et al. Memantine for dementia. Cochrane Database Syst Rev 2019; 3(6)CD003154
[PMID: 30891742]
[3]
Sugimoto H, Yamanishi Y, Iimura Y, Kawakami Y. Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr Med Chem 2000; 7(3): 303-39.
[http://dx.doi.org/10.2174/0929867003375191] [PMID: 10637367]
[4]
Ritchie CW, Ames D, Clayton T, Lai R. Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer disease. Am J Geriatr Psychiatry 2004; 12(4): 358-69.
[http://dx.doi.org/10.1097/00019442-200407000-00003] [PMID: 15249273]
[5]
Cheng DH, Tang XC. Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav 1998; 60(2): 377-86.
[http://dx.doi.org/10.1016/S0091-3057(97)00601-1] [PMID: 9632220]
[6]
Scarpini E, Scheltens P, Feldman H. Treatment of Alzheimer’s disease: current status and new perspectives. Lancet Neurol 2003; 2(9): 539-47.
[http://dx.doi.org/10.1016/S1474-4422(03)00502-7] [PMID: 12941576]
[7]
Rogers SL, Doody RS, Mohs RC, Friedhoff LT. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Arch Intern Med 1998; 158(9): 1021-31.
[http://dx.doi.org/10.1001/archinte.158.9.1021] [PMID: 9588436]
[8]
Kosasa T, Kuriya Y, Matsui K, Yamanishi Y. Inhibitory effects of donepezil hydrochloride (E2020) on cholinesterase activity in brain and peripheral tissues of young and aged rats. Eur J Pharmacol 1999; 386(1): 7-13.
[http://dx.doi.org/10.1016/S0014-2999(99)00741-4] [PMID: 10611458]
[9]
Radwan MA, Abdine HH, Al-Quadeb BT, Aboul-Enein HY, Nakashima K. Stereoselective HPLC assay of donepezil enantiomers with UV detection and its application to pharmacokinetics in rats. J Chromatogr B Analyt Technol Biomed Life Sci 2006; 830(1): 114-9.
[http://dx.doi.org/10.1016/j.jchromb.2005.10.031] [PMID: 16290074]
[10]
Pappa H, Farrú R, Vilanova PO, Palacios M, Pizzorno MT. A new HPLC method to determine Donepezil hydrochloride in tablets. J Pharm Biomed Anal 2002; 27(1-2): 177-82.
[http://dx.doi.org/10.1016/S0731-7085(01)00499-X] [PMID: 11682224]
[11]
Reddy U, Reddy KH, Bobbarala V, Penumajji S. RP- HPLC method development for the determination of assay of Donepezil hydrochloride. Int J Chem Anal Sci 2010; 1(4): 35-40.
[12]
Nakashima K, Itoh K, Kono M, Nakashima MN, Wada M. Determination of donepezil hydrochloride in human and rat plasma, blood and brain microdialysates by HPLC with a short C30 column. J Pharm Biomed Anal 2006; 41(1): 201-6.
[http://dx.doi.org/10.1016/j.jpba.2005.10.017] [PMID: 16321494]
[13]
Lu Y, Wen H, Li W, Chi Y, Zhang Z. Determination of donepezil hydrochloride in plasma by liquid chromatography-mass spectrometry. J Chromatogr Sci 2004; 42(5): 234-7.
[http://dx.doi.org/10.1093/chromsci/42.5.234] [PMID: 15189594]
[14]
Pillai S, Singhvi I. Application of orange dye for quantitation of donepezil hydrochloride from tablet formulation. Indian J Pharm Sci 2006; 68(5): 682-4.
[http://dx.doi.org/10.4103/0250-474X.29652]
[15]
Abbas SS, Fayez YM, Abdel Fattah Lel-S. Stability indicating methods for determination of Donepezil Hydrochloride according to ICH guidelines. Chem Pharm Bull (Tokyo) 2006; 54(10): 1447-50.
[http://dx.doi.org/10.1248/cpb.54.1447] [PMID: 17015988]
[16]
Sangshetti JN, Mahaparale PR, Paramane S, Shinde DB. Spectrophotometric estimation of donepezil hydrochloride in bulk and tablet formulation. Trends Appl Sci Res 2008; 3(1): 109-12.
[http://dx.doi.org/10.3923/tasr.2008.109.112]
[17]
Yasir M, Sara UVS, Chauhan I, et al. Solid lipid nanoparticles for nose to brain delivery of donepezil: formulation, optimization by Box–Behnken design, in vitro and in vivo evaluation. Artif Cells Nanomed Biotechnol 2018; 46(8)
[18]
Guo W, Quan P, Fan L, Cun D, Yang M. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study. Asian J Pharm Sci 2015; 10(2): 405-14.
[http://dx.doi.org/10.1016/j.ajps.2015.06.001]
[19]
Indian Pharmacopoeia. In: The indian pharmacopoeia commission, Ghaziabad. Delhi: The controller of publication. 1996. II: pp. A145-6.
[20]
Chadha R, Bhandari S. Drug-excipient compatibility screening--role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal 2014; 87(4): 82-97.
[http://dx.doi.org/10.1016/j.jpba.2013.06.016] [PMID: 23845418]
[21]
Rojanasthien N, Aunmuang S, Hanprasertpong N, Roongapinun S, Teekachunhatean S. Bioequivalence study of donepezil hydrochloride tablets in healthymale volunteers. ISRN Pharmacol 2012; 2012(1): 4-7.
[22]
Validation of analytical procedures: text and methodology International Conference on Harmonization, draft revised guidance on Q2 (R1) Current step 4 version 2005 November; 2005. November; 6-13.
[23]
Yasir M, Sara UVS, Som I. Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles. Br J Pharm Res 2017; 53(2): 1-13.
[24]
Holzer W. Unambiguous assignment of the 1H- and 13C-NMR spectra of propafenone and a thiophene analogue. Molecules 2001; 6(10): 796-802.
[http://dx.doi.org/10.3390/61000796]
[25]
Hanif M, Akhtar MF, Naeem S, et al. Development and validation of a new HPLC method for the detection of 5- fluorouracil in mobile phase and in plasma. Curr Pharm Anal 2018; 14(1): 3-7.


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Article Details

VOLUME: 10
ISSUE: 1
Year: 2020
Page: [48 - 62]
Pages: 15
DOI: 10.2174/2468187309666190923111541

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