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基于儿科生物药剂学考量研发适合儿童的迷你型卡维地洛口腔崩解片。

Development of an Age-Appropriate Mini Orally Disintegrating Carvedilol Tablet with Paediatric Biopharmaceutical Considerations.

作者信息

Khan Dilawar, Kirby Daniel, Bryson Simon, Shah Maryam, Mohammed Afzal Rahman

机构信息

Aston Pharmacy School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK.

Proveca Ltd., WeWork, No.1 Spinningfields, Quay Street, Manchester M3 3JE, UK.

出版信息

Pharmaceutics. 2021 Jun 3;13(6):831. doi: 10.3390/pharmaceutics13060831.

Abstract

Owing to considerable differences observed in anatomy and physiology between paediatric subsets, it has been well established that children respond to drugs differently compared to adults. Furthermore, from a formulation perspective, there is a distinct challenge to develop a dosage form that is capable of safely, accurately, and reliably delivering the dose across the whole paediatric population. Orally disintegrating mini-tablets (ODMT) have widely been considered as an age-appropriate formulation option that possess the ability for adequate dose flexibility, avoids swallowing difficulties, and exhibits superior stability due to its solid state. Within this study, two strengths (0.5 mg and 2 mg) of carvedilol ODMT formulations were developed using an excipient composition and load that is appropriate for paediatric use. The formulations demonstrated adequate mechanical strength (>20 N) and fast disintegration times (<30 s). Dissolution profiles observed were robust and comparable to the marketed conventional tablet formulation across various parts of the gastrointestinal (GI) tract in both the fed and fasted state, signifying appropriate efficacy, quality, and performance. As such, the formulations developed in this study show potential to address the need of an 'age-appropriate' formulation of carvedilol, as highlighted by the European Medicines Agency (EMA) Inventory of the Needs for Paediatric Medicine.

摘要

由于在儿科亚组之间观察到解剖学和生理学上存在相当大的差异,儿童对药物的反应与成人不同这一点已得到充分证实。此外,从制剂角度来看,开发一种能够在整个儿科人群中安全、准确且可靠地给药的剂型存在明显挑战。口腔崩解片(ODMT)已被广泛认为是一种适合儿童年龄的制剂选择,它具有剂量灵活性高、避免吞咽困难以及由于其固态而具有卓越稳定性的能力。在本研究中,使用适合儿科使用的辅料组成和用量,开发了两种规格(0.5毫克和2毫克)的卡维地洛口腔崩解片制剂。这些制剂表现出足够的机械强度(>20牛)和快速崩解时间(<30秒)。在进食和禁食状态下,观察到的溶出曲线稳定,并且在胃肠道(GI)的各个部位与市售常规片剂制剂相当,表明具有适当的疗效、质量和性能。因此,本研究中开发的制剂显示出满足卡维地洛“适合儿童年龄”制剂需求的潜力,正如欧洲药品管理局(EMA)儿科药品需求清单所强调的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e264/8227311/fbd1d8d67e79/pharmaceutics-13-00831-g001.jpg

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