DESIGN, DEVELOPMENT, AND EVALUATION OF TRANSDERMAL PATCHES CONTAINING MEMANTINE HYDROCHLORIDE

SUMAN KUMAR VALEVETI; SHAILAJA PASHIKANTI

doi:10.22159/ijap.2023v15i5.48481

Authors

SUMAN KUMAR VALEVETI A. U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh https://orcid.org/0009-0000-3135-6999
SHAILAJA PASHIKANTI A. U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh https://orcid.org/0000-0002-3796-7106

DOI:

https://doi.org/10.22159/ijap.2023v15i5.48481

Keywords:

Alzheimer’s disease, Transdermal patches, Memantine hydrochloride, Box-Behnken designs, Ex-vivo studies, In vivo studies

Abstract

Objective: This study aimed to develop an effective transdermal drug delivery system of memantine hydrochloride (MH), an anti-Alzheimer's drug, to improve patient compliance and optimize drug therapy in patients with dementia who often have difficulties adhering to oral medication schedules.

Methods: Various transdermal patches of MH were prepared using the box-Behnken design of experiments with different polymer combinations. The fabricated patches were evaluated for properties like thickness, folding endurance, drug content uniformity, in vitro drug release, and diffusion studies. An optimal formulation was selected based on the results and further studied for pharmacokinetic parameters in rabbits. The results were compared to conventional tablets containing the same polymer combination.

Results: Formulation B2 containing Hydroxy Propyl Methyl Cellulose (HPMC) 137.5 mg, Ethyl Cellulose (EC) 400 mg, and xanthan gum 300 mg had a flux of 212.24 μg/cm²/h, the permeability of 2.32 cm/h, and 27.95% release at 8h, with first-order and non-Fickian drug release kinetics. It was non-irritating, and in vitro release studies showed sustained release for up to 48 h. In vivo studies in rabbits also indicated superior drug absorption and sustained release from the patches compared to tablets.

Conclusion: The optimized transdermal patch formulation had the potential to provide a prolonged release of MH for over 2 d and reduce the frequency of dosing. However, further studies are warranted to confirm the efficacy, safety, and pharmacokinetics of the patches in human models before clinical use.

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References

Alam MI, Alam N, Singh V, Alam MS, Ali MS, Anwer T. Type, preparation and evaluation of transdermal patch: a review. World J Pharm Pharm Sci. 2013;2(4):2199-233.

Kanasty R, Low S, Bhise N, Yang J, Peeke E, Schwarz M. A pharmaceutical answer to nonadherence: once weekly oral memantine for Alzheimer’s disease. J Control Release. 2019;303:34-41. doi: 10.1016/j.jconrel.2019.03.022, PMID 30928488.

Calhoun A, King C, Khoury R, Grossberg GT. An evaluation of memantine ER+ donepezil for the treatment of Alzheimer’s disease. Expert Opin Pharmacother. 2018;19(15):1711-7. doi: 10.1080/14656566.2018.1519022, PMID 30244611.

Hardainiyan S, Kumar K, Nandy BC, Saxena R. Design, formulation and in vitro drug release from transdermal patches containing imipramine hydrochloride as model drug. Int J Pharm Pharm Sci. 2017 Jun 1;9(6):220. doi: 10.22159/ijpps.2017v9i6.16851.

Bashyal S, Shin CY, Hyun SM, Jang SW, Lee S. Preparation, characterization, and in vivo pharmacokinetic evaluation of polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels for transdermal delivery of donepezil HCl. Pharmaceutics. 2020;12(3):270. doi: 10.3390/pharmaceutics12030270, PMID 32188083.

Kearney MC, Caffarel Salvador E, Fallows SJ, McCarthy HO, Donnelly RF. Microneedle-mediated delivery of donepezil: potential for improved treatment options in Alzheimer’s disease. Eur J Pharm Biopharm. 2016;103:43-50. doi: 10.1016/j.ejpb.2016.03.026, PMID 27018330.

MNJ, Chandrakala V, Srinivasan S. An overview: recent development in transdermal drug delivery. Int J Pharm Pharm Sci. 2022 Oct 1:1-9.

Choudhory N, Kaur T, Singh AP, Singh AP. Formulation and evaluation of maslinic acid-loaded transdermal patches. Int J Curr Pharm Sci. 2021 Nov 15:89-98. doi: 10.22159/ijcpr.2021v13i6.1933.

Walbi IA, Ahmad MZ, Ahmad J, Algahtani MS, Alali AS, Alsudir SA. Development of a curcumin-loaded lecithin/chitosan nanoparticle utilizing a box-behnken design of experiment: formulation design and influence of process parameters. Polymers. 2022;14(18):3758. doi: 10.3390/polym14183758, PMID 36145903.

Choudhury D, Dutta KN, Kalita R. A review on transdermal patches used as an anti-inflammatory agent. Asian J Pharm Clin Res. 2021 Dec 7:21-6. doi: 10.22159/ajpcr.2021.v14i12.43277.

Allena RT, Yadav HK, Sandina S. Sarat Chandra Prasad M. Preparation and evaluation of transdermal patches of metformin hydrochloride using natural polymer for sustained release. Int J Pharm Pharm Sci. 2012;4(3):297-302.

Vithoba SR, Velraj M. Optimization, formulation and characterization of Nano based TDDS of eplerenone. Int J App Pharm. 2023 Jan 7:227-33. doi: 10.22159/ijap.2023v15i1.45433.

Bahazeq AA, Syeda WN, Isba NF, Rehman M, Baqi UA. Assay of memantine hydrochloride by UV spectrophotometer. Int J Pharm Sci Res. 2019;10(1):27-30.

Alshetaili A, Almutairy BK, Alshehri SM, Repka MA. Development and characterization of sustained-released donepezil hydrochloride solid dispersions using hot melt extrusion technology. Pharmaceutics. 2021;13(2):213. doi: 10.3390/pharmaceutics13020213, PMID 33557076.

Chaurasia G. A review on pharmaceutical preformulation studies in formulation and development of new drug molecules. Int J Pharm Sci Res. 2016;7(6):2313-20.

Santhosam RD, Kannan S, Devi SL. Development and validation of RP-HPLC method for estimation of donepezil HCl from bulk and marketed dosage forms. J Chem Pharm Res. 2010;2(6):62-7.

Atia NN, Marzouq MA, Hassan AI, Eltoukhi WE. A rapid FTIR spectroscopic assay for the quantitative determination of memantine hydrochloride and amisulpride in human plasma and pharmaceutical formulations. Spectrochim Acta A Mol Biomol Spectrosc. 2020;236:118377. doi: 10.1016/j.saa.2020.118377, PMID 32330826.

Amjad M, Ehtheshamuddin M, Chand S, Hanifa SM, Asia R, Kumar GS. Formulation and evaluation of transdermal patches of atenolol. Adv Res Pharm Biol. 2011;1(2):12-23.

Saxena M, Mutalik S, Reddy MS. Formulation and evaluation of transdermal patches of metoclopramide hydrochloride. Indian Drugs. 2006;43(9):740-5.

Tanwar YS, Chauhan CS, Sharma A. Development and evaluation of carvedilol transdermal patches. Acta Pharm. 2007;57(2):151-9. doi: 10.2478/v10007-007-0012-x, PMID 17507312.

Patel RP, Patel G, Baria A. Formulation and evaluation of transdermal patch of aceclofenac. Int J Drug Del;1(1):41-51. doi: 10.5138/ijdd.2009.0975.0215.01005.

Bhatia C, Sachdeva M, Bajpai M. Formulation and evaluation of transdermal patch of pregabalin. Int J Pharm Sci Res. 2012;3(2):569.

Atılay Takmaz EA, Yener G. Effective factors on iontophoretic transdermal delivery of memantine and donepezil as model drugs. J Drug Deliv Sci Technol. 2021;63:102438. doi: 10.1016/j.jddst.2021.102438.

Kumar SS, Behury B, Sachinkumar P. Formulation and evaluation of transdermal patch of stavudine. Dhaka Univ J Pharm Sci. 2013;12(1):63-9. doi: 10.3329/dujps.v12i1.16302.

Mohabe V, Akhand R, Pathak AK. Preparation and evaluation of captopril transdermal patches. Boll Pharm Res. 2011;1(2):47-52.

Ganti SS, Bhattaccharjee SA, Murnane KS, Blough BE, Banga AK. Formulation and evaluation of 4-benzylpiperidine drug-in-adhesive matrix type transdermal patch. Int J Pharm. 2018;550(1-2):71-8. doi: 10.1016/j.ijpharm.2018.08.033, PMID 30125654.

Kusum Devi V, Saisivam S, Maria GR, Deepti PU. Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride. Drug Dev Ind Pharm. 2003;29(5):495-503. doi: 10.1081/ddc-120018638, PMID 12779279.

Kriplani P. Formulation and evaluation of transdermal patch of diclofenac sodium. GJPPS 2018;4(5). doi: 10.19080/GJPPS.2018.04.555647.

Jayaprakash S, Halith SM, Firthouse PM, Yasmin YM, Nagarajan M. Preparation and evaluation of celecoxib transdermal patches. Pak J Pharm Sci. 2010;23(3):279-83. PMID 20566440.

Shivalingam MR, Balasubramanian A, Ramalingam K. Formulation and evaluation of transdermal patches of pantoprazole sodium. Int J App Pharm. 2021 Sep 7:287-91. doi: 10.22159/ijap.2021v13i5.42175.

Singh A, Bali A. Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride. J Anal Sci Technol. 2016 Nov 28;7(1):25. doi: 10.1186/s40543-016-0105-6.

Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31. doi: 10.4103/0976-0105.177703, PMID 27057123.

Sheth NS, Mistry RB. Formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol. J Appl Pharm Sci. 2011;(Issue):96-101.

Banker GS. The theory and practice of industrial pharmacy. J Pharm Sci. 1970 Oct;59(10):1531.

Bala R, Sharma S. Formulation optimization and evaluation of fast dissolving film of aprepitant by using design of experiment. Bull Fac Pharm Cairo Univ. 2018;56(2):159-68. doi: 10.1016/j.bfopcu.2018.04.002.

Roy H. Box-Behnken design for optimization of formulation variables for fast dissolving tablet of urapidil. Asian J Pharm AJP. 2018;12(03).

Elballa W, Salih M. Influence of partially and fully pregelatinized starch on the physical and sustained-release properties of hpmc-based ketoprofen oral matrices. Int J Pharm Pharm Sci. 2022 Aug 1:29-34. doi: 10.22159/ijpps.2022v14i8.45031.

Farooqui P, Gude R. Formulation development and optimisation of fast dissolving buccal films loaded glimepiride solid dispersion with enhanced dissolution profile using central composite design. Int J Pharm Pharm Sci. 2023 Jun 1;15(6):35-54. doi: 10.22159/ijpps.2023v15i6.47992.

Shinde R, Velraj M. Formulation, optimization, and characterization of transdermal drug delivery systems containing eplerenone. Int J App Pharm. 2022 Jan 7;14(1):198-207. doi: 10.22159/ijap.2022v14i1.42827.