Formulation and clinical evaluation of carbidopa/levodopa oral solution for the treatment of sepiapterin reductase deficiency

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Evelina Maines , Giorgio Temporin , Michela Fedrizzi , Alessandra Pasqualini , Lorenzo Junior Masnata , Annalisa Campomori , Alessandro Iodice , Giovanni Piccoli , Massimo Soffiati , Roberto Franceschi , Silvana Anna Maria Urru
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引用次数: 0

Abstract

Background

sepiapterine reductase deficiency (SRD) is a rare levodopa (L-dopa)-responsive disorder treated with a combination therapy of controlled-release L-dopa and carbidopa. The currently available formulation of controlled-release carbidopa/L-dopa does not entirely meet the requirements for the long-term therapy in pediatric patients. In fact, administration of a manufactured tablet at a dose intended for adults necessitates its adjustment to the child’s needs, as the splitting of the tablet into smaller portions or its dilution in water. It’s essential to emphasize that tablets must not be crushed, as this can compromise the controlled-release mechanism and affect the efficacy of the medication. At the moment, commercial liquid formulations are not available. Given these limitations, in house drug preparation in hospitals and community pharmacies is a valid option to ensure the proper therapeutic management of these patients.

Materials and methods

we described sample preparation, physical and microbiological analyses, taste testing, and tolerability of a 1:10 ratio carbidopa/L-dopa flavored (mint, raspberry, cacao, berries) and unflavored oral formulation (no sweetening agents were added). We also reported long-term follow-up of two pediatric patients with SRD.

Results

we documented the stability for 28 days at 25 °C of the liquid solution. All formulations were well-tolerated, and no adverse events were observed during or after assessing taste and tolerability. The long-term follow up of two patients was characterized by effective symptom control and optimal treatment adherence and compliance.

Conclusions

in-house liquid drug formulations can be a valid option for pediatric patients with SRD. Given the significant impact of taste on medication adherence, the use of flavoring agents in the development of liquid formulations of L-dopa/carbidopa results a very useful strategy to obtain optimal adherence in the pediatric population.

用于治疗sepiapterin还原酶缺乏症的卡比多巴/左旋多巴口服溶液的配方和临床评估。
背景:sepiapterine还原酶缺乏症(SRD)是一种罕见的左旋多巴(L-多巴)反应性疾病,可通过控释左旋多巴和卡比多巴联合疗法进行治疗。目前可用的卡比多巴/左旋多巴控释制剂并不完全符合儿童患者长期治疗的要求。事实上,如果按成人剂量服用已制成的药片,就必须根据儿童的需要进行调整,如将药片分成小份或用水稀释。必须强调的是,药片不能压碎,否则会破坏控释机制,影响药效。目前还没有商业液体制剂。材料和方法:我们介绍了 1:10 比例的卡比多巴/多巴风味(薄荷、覆盆子、可可、浆果)和无味口服制剂(未添加甜味剂)的样品制备、物理和微生物分析、口味测试和耐受性。我们还报告了对两名患有SRD的儿童患者的长期随访结果:我们记录了液体溶液在25°C下28天的稳定性。所有制剂的耐受性都很好,在评估口感和耐受性期间或之后均未发现不良反应。对两名患者的长期随访显示,他们的症状得到了有效控制,治疗的依从性和顺应性也达到了最佳水平。鉴于口感对服药依从性的重要影响,在开发左旋多巴/卡比多巴液体制剂时使用调味剂是一项非常有用的策略,可使儿科患者获得最佳的服药依从性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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