A COMPREHENSIVE DESIGN EXPERT SCREENING APPROACH FOR  OPTIMIZING THE TRANSDERMAL DONEPEZIL DELIVERY IN  ALZHEIMER'S DISEASE MANAGEMENT

Bariki Rajasekhar; Haranath Chinthaginjala

doi:10.48165/abr.2024.26.01.62

Authors

Bariki Rajasekhar Department of Pharmaceutical Sciences, JNTUA, Ananthapuramu – 515 001, Andhra Pradesh (India) 2
Haranath Chinthaginjala Department of Pharmaceutics, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K. R. Palli Cross, Ananthapuramu – 515 721, Andhra Pradesh (India)

DOI:

https://doi.org/10.48165/abr.2024.26.01.62

Keywords:

Design, donepezil, flexibility, permeation, transdermal patches

Abstract

Transdermal patches offer a significant advantage for systemic Donepezil (DPZ) absorption by bypassing hepatic first-pass metabolism, which otherwise produces inactive Donepezil N-oxide and other hydroxylated metabolites. These patches enable the controlled and continuous release of medication into the bloodstream through intact skin over an extended period.This study aimed to develop and characterize DPZ transdermal patches using a central composite design. The patches were prepared with PVP K30, HPMC K15, and modified chitosan through the solvent-casting technique. The central composite design generated by Design Expert software was used to analyze the impact of independent variables on the response.FTIR analysis was conducted to examine DPZ-excipient interactions. The formulations of Donepezil transdermal patches (DTDP) demonstrated excellent physicochemical properties, including appearance, thickness, weight uniformity, folding endurance (FE), elongation at break, DPZ content, moisture content, and tensile strength. Among the formulations, DTDP-11 exhibited the highest DPZ release at 8, 16, and 24 hours.The patches were flexible, with a breakpoint at 161 folds. Tensile strength across all batches ranged between 0.422 and 0.433 mg cm⁻² h⁻¹, and the moisture content was within acceptable limits. In vitro testing confirmed consistent DPZ permeation across all patches, with DTDP-11 showing the best performance, indicating enhanced DPZ release.The study concluded that using HPMC K15 (125 mg), PVP K30 (40 mg), and modified chitosan (65.9 mg) effectively facilitated prolonged permeation and flexibility in DPZ transdermal patches.

Downloads

Download data is not yet available.

References

Adelman, M. and Louis, L. 2023. A novel formulation: Donepezil patch. The Senior Care Pharmacist, 38(7): 300-304.

Adlimoghaddam, A., Neuendorff, M., Roy, B. and Albensi, B.C. 2018. A review of clinical treatment considerations of donepezil in severe Alzheimer's disease. CNS Neuroscience and Therapeutics, 24(10): 876-88.

Ahad, H.A., Ishaq, B.M., Shaik, M. and Bandagisa, F. 2016. Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone. Pakistan Journal of Pharmaceutical Sciences, 29(3): 945-951.

Ahad, H.A., Kumar, C.S., Anuradha, C. and Reddy, K.K. 2011. A novel mucilage from Ficus glomerata fruits for transdermal patches: Taking indomethacin as a model drug. Iranian Journal of Pharmaceutical Sciences, 7(1): 25-36.

550 Bariki Rajasekhar and Haranath Chinthaginjala

Alhaushey, L. and Ahmad, R.D. 2023. Formulation and evaluation of celecoxib transdermal patches. Research Journal of Pharmacy and Technology, 16(4): 1574-1580.

Alzheimer's Association. 2019. Alzheimer's disease facts and figures. Alzheimer's & Dementia, 15(3): 321-387.

Amarachinta, P.R., Sharma, G., Samed, N., Chettupalli, A.K., Alle, M. and Kim, J.C. 2021. Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect. Journal of Nanobiotechnology, 19 (1): 1-5.

Ashfaq, A., Riaz, T., Waqar, M.A., Zaman, M. and Majeed, I. 2024. A comprehensive review on transdermal patches as an efficient approach for the delivery of drug. Polymer-Plastics Technology and Materials, 63(8): 1045-1069.

Buck, A., Rezaei, K., Quazi, A., Goldmeier, G., Silverglate, B. and Grossberg, G.T. 2024. The donepezil transdermal system for the treatment of patients with mild, moderate, or severe Alzheimer’s disease: A critical review. Expert Review of Neurotherapeutics, 24(6): 607-614.

Dinh, L., Lee, S., Abuzar, S.M., Park, H. and Hwang, S.J. 2022. Formulation, preparation, characterization, and evaluation of dicarboxylic ionic liquid donepezil transdermal patches. Pharmaceutics, 14(1): 205-220.

Jajoo, V.S., Shrirame, D.S., Sawale, A.V. and Atram, S.C. 2023. Formulation and evaluation of transdermal patch for the treatment of migraine. Journal of Drug Delivery and Therapeutics, 13(5): 47-52.

Jyothika, L.S.K., Ahad, H.A., Haranath, C., Kousar, S., Pal Gowd, H.D. and Sadiya, S.H. 2022. Types of transdermal drug delivery systems: A literature report of the past decade. Research Journal of Pharmaceutical Dosage Form and Technology, 14(2): 157-162.

Khan, D., Qindeel, M., Ahmed, N., Khan, A.U., Khan, S. and Rehman, A.U. 2020. Development of novel pH-sensitive nanoparticle-based transdermal patch for management of rheumatoid arthritis. Nanomedicine, 15(6): 603-624.

Kılıçaslan, D.J.C.S.J. 2024. Donepezil-squaric acid hybrid: Synthesis, characterization and investigation of anticholinesterase inhibitory, DNA binding and antioxidant properties. 45(2): 216-226.

Kriplani, P., Guarve, K. and Baghel, U.S. 2021. Formulation optimization and characterization of transdermal film of curcumin by response surface methodology. Chinese Herbal Medicines, 13(2): 274-285.

Kusuma, K., Subhash, P., Ahad, H.A., Poojari, S.J. and Abhishek, J. 2024. Deciphering the puzzle: A thorough examination of microsphere optimization through factorial design methodology, unveiling novel strategies and promising directions. Naturalista Campano, 28(1): 3143-3155.

Lee, B., Mahtab, M., Neo, T., Farooqi, I. and Khursheed, A.J.J. 2022. A comprehensive review of design of experiment (DOE) for water and wastewater treatment application - Key concepts, methodology and contextualized application. Journal of Water Process Engineering, 47(1): 102673. [https://doi.org/10.1016/j.jwpe.2022.102673].

Magalhães, S., Goodfellow, B.J. and Nunes, A.J.A.S.R. 2021. FTIR spectroscopy in biomedical research: How to get the most out of its potential. Applied Spectroscopy Reviews, 56(8): 869-907. Mohamed, F.A., Khashaba, P.Y., Shahin, R.Y. and El-Wekil, M.M. 2019. Tunable ternary nanocomposite prepared by electrodeposition for biosensing of centrally acting reversible acetyl cholinesterase inhibitor donepezil hydrochloride in real samples. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 567(1): 76-85.

Nakamura, Y., Kim, R., Nishiyama, K., Kikuchi, T., Ishikawa, I. and Aoki, H. 2023. Efficacy and safety of a transdermal donepezil patch in patients with mild‐to‐moderate Alzheimer's disease: A 24‐week, randomized, multicenter, double‐blind, parallel group, non‐inferiority study. Geriatrics & Gerontology International, 23(4): 275-281.

Padmaja, B. and Rani, S.S. 2024. Development of rosuvastatin calcium nano-carrier patches by central composite design. GSC Biological and Pharmaceutical Sciences, 27(3): 123-133.

Design expert approach for optimizing transdermal donepezil delivery 551

Pandey, A. and Gupta, S. 2023. Evaluation of formulated transdermal patches. Journal of Population Therapeutics and Clinical Pharmacology, 30(16): 793-798.

Pandey, P. and Pandey, M.M. 2021. Research Methodology Tools and Techniques. Bridge Center, Buzau, Romania.

Prabhu, K., Prabhu, P., Bhat, P. and Patil, S. 2021. Development and validation of a UV spectro photometric method for the estimation of donepezil hydrochloride in bulk and pharmaceutical formulations. Asian Journal of Pharmaceutical and Clinical Research, 14(1): 61-66.

Shravani, Y., Ahad, H.A., Haranath, C., Gari Poojitha, B., Rahamathulla, S. and Rupasree, A. 2021. Past decade work done on cubosomes using factorial design: A fast track information for researchers. International Journal of Life Sciences and Pharmaceutical Research, 11(1): 124- 135.

Shiyan, S., Marketama, M.M. and Pratiwi, G. 2021. Optimization transdermal patch of polymer combination of chitosan and HPMC-loaded ibuprofen using factorial designs. Pharmaciana, 11(3): 406-415.

Siafaka, P.I., Bülbül, E.Ö., Mutlu, G., Okur, M.E., Karantas, I.D., Okur, N.Ü.J.C. and Targets, N.D.D. 2020. Transdermal drug delivery systems and their potential in Alzheimer’s disease management. Journal of Current Drug Delivery, 19(5): 360-373.

Somadasan, S., Subramaniyan, G., Athisayaraj, M.S. and Sukumaran, S.K. 2024. Central composite design: An optimization tool for developing pharmaceutical formulations. Journal of Young Pharmacists, 16(3): 400-409.

Suksaeree, J., Maneewattanapinyo, P., Panrat, K., Pichayakorn, W., Monton, C.J.J.O.P. 2021. Solvent‐cast polymeric films from pectin and Eudragit® NE 30D for transdermal drug delivery systems. Journal of Polymers and the Environment, 29(1): 3174-3184.

Yongping, Z.H., Jian, X.U. and Weijie, X.I. 2028. Optimization of the matrix formulation of new indomethacin hydrophilic gel patches based on central composite design-response surface methodology and its molding process inspection. Herald of Medicine, 37(5): 593-599.

Zhang, X., Lian, S., Zhang, Y. and Zhao, Q. 2022. Efficacy and safety of donepezil for mild cognitive impairment: A systematic review and meta-analysis. Clinical Neurology and Neurosurgery, 213(1): 107134. [https://doi.org/10.1016/j.clineuro.2022.107134].