Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology

Author:

Alalaiwe Ahmed1ORCID,Alsenaidy Mohammad A.2,Almalki Ziyad S.3ORCID,Fayed Mohamed H.4ORCID

Affiliation:

1. Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia

2. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

3. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia

4. Department of Pharmaceutics, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt

Abstract

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10–40% w/w) and partially pre-gelatinized starch (PPGS; 2–10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

Funder

Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia

Publisher

MDPI AG

Subject

Pharmaceutical Science

Reference25 articles.

1. Management of Pulmonary Hypertension in the Pediatric Patient;Epstein;Cardiol. Clin.,2022

2. Effectiveness and short-term survival associated with adding sildenafil to conventional therapy in the management of children with pulmonary hypertension;William;Prog. Pediatr. Cardiol.,2020

3. Design and physicochemical stability studies of paediatric oral formulations of sildenafil;Provenza;Int. J. Pharm.,2014

4. Orally disintegrating mini-tablets (ODMTs)—A novel solid oral dosage form for paediatric use;Stoltenberg;European J. Pharm. Biopharm.,2011

5. WHO (World Health Organisation) (2023, February 19). 3, Flexible Solid Oral Dosage: Dispersible Formulations of Amoxicillin, Revised WHO Classification and Treatment of Pneumonia in Children at Health Facilities: Evidence Summaries, Available online: https://www.ncbi.nlm.nih.gov/books/NBK264163/.

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3