Optimization and evaluation of transdermal delivery system for nebivolol hydrochloride
DOI:
https://doi.org/10.69857/joapr.v12i3.580Keywords:
Transdermal drug delivery, Hypertension, Nebivolol hydrochloride, Central composite designAbstract
Background: Nebivolol hydrochloride, a β1-receptor antagonist known for its antihypertensive properties, boasts a plasma half-life of 10 hours and an oral bioavailability of 12%. In this study, we aimed to enhance the therapeutic effectiveness of Nebivolol hydrochloride and circumvent its extensive hepatic first-pass metabolism by developing transdermal matrix patches. Methodology: Utilizing Central Composite Design (CCD), nine formulations were devised, comprising Hydroxypropyl methylcellulose K15M and Eudragit S100 as independent variables, with 10% w/w triethyl citrate as the plasticizer. Key dependent variables were evaluated, including folding endurance, moisture content, tensile strength, in vitro drug release, and flux. Fourier transform infrared spectroscopy (FTIR) assessed the compatibility between the drug and polymer. Results and discussion: Among the formulations, FP8 demonstrated the highest drug release (85.88% over 24 hours), attributed to its elevated concentration of hydrophobic polymer. The optimized formulation was determined based on the results of dependent variables. Conclusion: These findings suggest that the developed matrix transdermal film holds promise as a potential candidate for sustained drug release over a 24-hour.
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Baryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nature Reviews Drug Discovery, 22, 387–409 (2023).
Vora D, Dandekar A, Bhattaccharjee S, Singh ON, Agrahari V, Peet MM, et al. Formulation development for transdermal delivery of raloxifene, a chemoprophylactic agent against breast cancer. Pharmaceutics, 14, 680 (2022).
Agrawal S, Gandhi SN, Gurjar P, Saraswathy N. Microneedles: An advancement to transdermal drug delivery system approach. Journal of Applied Pharmaceutical Science, 10, 149–159 (2020).
Adepu S, Ramakrishna S. Controlled drug delivery systems: current status and future directions. Molecules, 26, 5905 (2021).
Sabbagh F, Kim BS. Recent advances in polymeric transdermal drug delivery systems. Journal of Controlled Release, 341, 132–146 (2022).
Hemrajani C, Negi P, Parashar A, Gupta G, Jha NK, Singh SK, et al. Overcoming drug delivery barriers and challenges in topical therapy of atopic dermatitis: A nanotechnological perspective. Biomedicine & Pharmacotherapy, 147, 112633 (2022).
Halder S, Chakraborty P, Pradhan D, Bagchi A. Recent advancement in the method of transdermal drug delivery system: A review. Journal of Applied Pharmaceutical Research, 9, 06–09 (2021).
Üstündağ-Okur N, Yurdasiper A, Gündoğdu E, Homan Gökçe E. Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for improvement of oral bioavailability in treatment of hypertension: Polyethylene glycol versus chitosan oligosaccharide lactate. Journal of Microencapsulation, 33, 30–42 (2016).
Maslov LN, Naryzhnaya NV, Voronkov NS, Kurbatov BK, Derkachev IA, Ryabov VV, Vyshlov EV, Kolpakov VV, Tomilova EA, Sapozhenkova EV, Singh N, Fu F, Pei J. The role of β-adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β-adrenergic receptor agonists and antagonists protect the heart. Fundam Clin Pharmacol, 38, 658-73 (2024).
Farhoumand LS, Liu H, Tsimpaki T, Hendgen-Cotta UB, Rassaf T, Bechrakis NE, et al. Blockade of β-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures. International Journal of Molecular Sciences, 24, 5894 (2023).
Farmoudeh A, Rezaeiroshan A, Abbaspour M, Nokhodchi A, Ebrahimnejad P. Solid dispersion pellets: an efficient pharmaceutical approach to enrich the solubility and dissolution rate of deferasirox. BioMed Research International, 2020, 8583540 (2020).
Liu C, Guan Y, Tian Q, Shi X, Fang L. Transdermal enhancement strategy of ketoprofen and teriflunomide: the effect of enhanced drug-drug intermolecular interaction by permeation enhancer on drug release of compound transdermal patch. International Journal of Pharmaceutics, 572, 118800 (2019).
Singh A, Bali A. Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride. Journal of Analytical Science and Technology, 7, 25 (2016).
Garala KC, Shah PH. Influence of crosslinking agent on the release of drug from the matrix transdermal patches of HPMC/Eudragit RL 100 polymer blends. Journal of Macromolecular Science®, Part A: Pure and Applied Chemistry, 47, 273–281 (2010).
Shinde AJ, Garala KC, More HN. Development and characterization of transdermal therapeutics system of tramadol hydrochloride. Asian Journal of Pharmaceutics, 2 (4), 265 – 269 (2008).
Ghanma R, Naser YA, Kurnia Anjani Q, Hidayat Bin Sabri A, Hutton ARJ, Vora LK, Himawan A, Moreno-Castellanos N, Greer B, McCarthy HO, Paredes AJ, Donnelly RF. Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management. Int J Pharm, 660, 124342 (2024).
Buddhadev SS, C Garala K, S S, Rahamathulla M, Ahmed MM, Farhana SA, Pasha I. Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance. Drug Deliv, 31, 2288801 (2024).
Panda AK, Ramachandran D, Singh A, Thirumurugesan R, Mythili R. The effect of orientation and pore size on nano mechanical behaviour of Ag thin films: a comparison between experiment and atomistic simulation. Philosophical Magazine, 102, 2119–2162 (2022).
Dudhipala N, Phasha Mohammed R, Adel Ali Youssef A, Banala N. Effect of lipid and edge activator concentration on development of aceclofenac-loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation. Drug Development and Industrial Pharmacy, 46, 1334–1344 (2020).
Miranda M, Cova T, Augusto C, Pais AA, Cardoso C, Vitorino C. Diving into Batch-to-Batch Variability of Topical Products-a Regulatory Bottleneck. Pharmaceutical Research, 37, 1–17 (2020).
Kaur P, Alam T, Singh H, Jain J, Singh G, Broadway A. Organic Acids Modified Starch–CMC Based Biodegradable Film: Antibacterial Activity, Morphological, Structural, Thermal, and Crystalline Properties. Journal of Pure & Applied Microbiology, 17, 241 – 257 (2023).
Shirohiwala R, Rampurawala M, Agrawal V, Chinwala F, Patel M, Shah C, et al. Analysis of critical material attributes (CMAs) effect on aceclofenac transdermal patch. Pharma Science Monitor, 14, 111 – 127 (2023).
Kharia A, Singhai A, Gilhotra R. Formulation and evaluation of transdermal patch for the treatment of inflammation. Journal of Pharmaceutical Sciences and Research, 12, 780–788 (2020).
Pandey A, Gupta S. Evaluation of formulated transdermal patches. Journal of Population Therapeutics and Clinical Pharmacology, 30, 793–798 (2023).
Sheshala R, Anuar NK, Abu Samah NH, Wong TW. In vitro drug dissolution/permeation testing of nanocarriers for skin application: A comprehensive review. AAPS PharmSciTech, 20, 1–28 (2019).
Ansari M, Kazemipour M, Aklamli M. The study of drug permeation through natural membranes. International Journal of Pharmaceutics, 327, 6–11 (2006).
Rajesh G, Ramarao A, Sujitha P, Parveen M. Formulation and in vitro evaluation of naloxone transdermal patches. International Journal of Pharmacy & Therapeutics, 8(4), 160-169 (2017)
Song Y, Cong Y, Wang B, Zhang N. Applications of Fourier transform infrared spectroscopy to pharmaceutical preparations. Expert Opinion on Drug Delivery, 17, 551–571 (2020).
Bernal-Chávez SA, Romero-Montero A, Hernández-Parra H, Peña-Corona SI, Del Prado-Audelo ML, Alcalá-Alcalá S, et al. Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach. Journal of Biological Engineering, 17, 35 (2023).
Buya AB, Beloqui A, Memvanga PB, Préat V. Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery. Pharmaceutics, 12, 1194 (2020).
Raval MK, Garala KC, Patel JM, Parikh RK, Sheth NR. Functionality improvement of Chlorzoxazone by crystallo-co-agglomeration using multivariate analysis approach. Particulate Science and Technology, 39, 689–711 (2021).
Prodduturi S, Manek RV, Kolling WM, Stodghill SP, Repka MA. Water vapor sorption of hot‐melt extruded hydroxypropyl cellulose films: Effect on physico‐mechanical properties, release characteristics, and stability. Journal of Pharmaceutical Sciences, 93, 3047–3056 (2004).
Chevala NT, Jitta SR, Marques SM, Vaz VM, Kumar L. Polymeric microneedles for transdermal delivery of nanoparticles: Frontiers of formulation, sterility and stability aspects. Journal of Drug Delivery Science and Technology, 65, 102711 (2021).
Can AS, Erdal MS, Güngör S, Özsoy Y. Optimization and characterization of chitosan films for transdermal delivery of ondansetron. Molecules, 18, 5455–5471 (2013).
Garala K, Patel J, Patel A, Raval M, Dharamsi A. Influence of excipients and processing conditions on the development of agglomerates of racecadotril by crystallo-co-agglomeration. International Journal of Pharmaceutical Investigation, 2, 189 (2012).
Garala KC, Patel JM, Dhingani AP, Dharamsi AT. Quality by design (QbD) approach for developing agglomerates containing racecadotril and loperamide hydrochloride by crystallo-co-agglomeration. Powder Technology, 247, 128–146 (2013).
Takeuchi Y, Ikeda N, Tahara K, Takeuchi H. Mechanical characteristics of orally disintegrating films: Comparison of folding endurance and tensile properties. International Journal of Pharmaceutics, 589, 119876 (2020).
Das S, Sarkar P, Majee SB. Polymers in Matrix Type Transdermal Patch. International Journal of Pharmaceutical Sciences Review and Research, 73, 77–86 (2022).
Sharma A, Puri V, Kumar P, Singh I. Rifampicin-Loaded Alginate-Gelatin Fibers Incorporated within Transdermal Films as a Fiber-in-Film System for Wound Healing Applications. Membranes (Basel), 11, 7 (2020).
Malviya R, Tyagi A, Fuloria S, Subramaniyan V, Sathasivam K, Sundram S, et al. Fabrication and Characterization of Chitosan—Tamarind Seed Polysaccharide Composite Film for Transdermal Delivery of Protein/Peptide. Polymers, 13, 1531 (2021).
Phatale V, Vaiphei KK, Jha S, Patil D, Agrawal M, Alexander A. Overcoming skin barriers through advanced transdermal drug delivery approaches. Journal of Controlled Release, 351, 361–380 (2022).
Riccio BVF, Silvestre ALP, Meneguin AB, Ribeiro TdC, Klosowski AB, Ferrari PC, et al. Exploiting polymeric films as a multipurpose drug delivery system: a review. AAPS PharmSciTech, 23, 269 (2022).
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