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直接压片法制备氯沙坦口腔崩解片:提高儿科患者顺应性的经济有效方法。

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

机构信息

Departamento de Biología, Bioquímica y Farmacia-Universidad Nacional del Sur (UNS), Bahía Blanca, Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Buenos Aires, Argentina.

出版信息

AAPS PharmSciTech. 2024 Apr 8;25(4):79. doi: 10.1208/s12249-024-02796-9.

Abstract

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

摘要

开发合适的剂型对于儿童有效的药物治疗至关重要。口腔崩解片(ODTs)是一种有吸引力的剂型,它可以避免吞咽问题,确保剂量准确,并且易于给药,因为它在口腔中崩解。本研究旨在开发含有氯沙坦钾(LP)的 ODT 用于治疗儿童动脉高血压。通过直接压片的具有成本效益的制造工艺生产的 ODT 由稀释剂、超级崩解剂、助流剂和润滑剂的混合物组成。测试了五种超级崩解剂(交联羧甲基纤维素钠、两种等级的交联聚维酮、交联羧甲基淀粉钠和预胶化淀粉)(两种浓度),并与三种稀释剂(甘露醇、乳糖和山梨糖醇)结合。因此,根据崩解时间、硬度和脆性,评估了三十种制剂。两种表现出最佳崩解时间(<30 s)、硬度和脆性(≤1.0%)结果的制剂被选为进一步评估的最有前途的制剂。这些 ODTs 表现出良好的药物-赋形剂相容性、可压性和流动性能。体外溶出研究表明药物具有“非常快速”的释放。初步稳定性研究强调了需要进行保护性包装。在密封容器中储存 12 个月后,所有质量特性均保留了适当的结果。总之,成功开发和表征了 ODTs,表明有可能开发出最终原型,从而改善儿童动脉高血压的治疗效果。

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