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Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset o...

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Autores principales: AlAli, Amer S., Aldawsari, Mohammed F., Alalaiwe, Ahmed, Almutairy, Bjad K., Al-Shdefat, Ramadan, Walbi, Ismail A., Fayed, Mohamed H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231530/
https://www.ncbi.nlm.nih.gov/pubmed/34204781
http://dx.doi.org/10.3390/pharmaceutics13060870
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author AlAli, Amer S.
Aldawsari, Mohammed F.
Alalaiwe, Ahmed
Almutairy, Bjad K.
Al-Shdefat, Ramadan
Walbi, Ismail A.
Fayed, Mohamed H.
author_facet AlAli, Amer S.
Aldawsari, Mohammed F.
Alalaiwe, Ahmed
Almutairy, Bjad K.
Al-Shdefat, Ramadan
Walbi, Ismail A.
Fayed, Mohamed H.
author_sort AlAli, Amer S.
collection PubMed
description Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 3(2) full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in C(max) and AUC(0)–∞ with short t(max) compared to the market product (Viagra(®)). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.
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spelling pubmed-82315302021-06-26 Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique AlAli, Amer S. Aldawsari, Mohammed F. Alalaiwe, Ahmed Almutairy, Bjad K. Al-Shdefat, Ramadan Walbi, Ismail A. Fayed, Mohamed H. Pharmaceutics Article Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 3(2) full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in C(max) and AUC(0)–∞ with short t(max) compared to the market product (Viagra(®)). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance. MDPI 2021-06-12 /pmc/articles/PMC8231530/ /pubmed/34204781 http://dx.doi.org/10.3390/pharmaceutics13060870 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
AlAli, Amer S.
Aldawsari, Mohammed F.
Alalaiwe, Ahmed
Almutairy, Bjad K.
Al-Shdefat, Ramadan
Walbi, Ismail A.
Fayed, Mohamed H.
Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title_full Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title_fullStr Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title_full_unstemmed Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title_short Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique
title_sort exploitation of design-of-experiment approach for design and optimization of fast-disintegrating tablets for sublingual delivery of sildenafil citrate with enhanced bioavailability using fluid-bed granulation technique
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231530/
https://www.ncbi.nlm.nih.gov/pubmed/34204781
http://dx.doi.org/10.3390/pharmaceutics13060870
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