Self‐micellizing solid dispersion of tacrolimus: Physicochemical and pharmacokinetic characterization

生物利用度 结晶度 药代动力学 再结晶(地质) 无定形固体 化学 口服 溶解度 吸收(声学) 材料科学 溶解 色谱法 核化学 药理学 有机化学 医学 结晶学 古生物学 复合材料 生物
作者
Keisuke Makino,Ryota Tsukada,Atsushi Kambayashi,Kohei Yamada,Hideyuki Sato,Satomi Onoue
出处
期刊:Biopharmaceutics & Drug Disposition [Wiley]
卷期号:44 (6): 387-395
标识
DOI:10.1002/bdd.2373
摘要

Abstract The present study was undertaken to develop a self‐micellizing solid dispersion (SMSD) of tacrolimus (TAC) to improve the biopharmaceutical properties of TAC. An SMSD formulation of TAC (SMSD/TAC) and amorphous solid dispersion formulation of TAC (ASD/TAC) were prepared with Soluplus ® , an amphiphilic copolymer, and hydroxypropyl cellulose, respectively. Physicochemical properties were characterized in terms of morphology, crystallinity, storage stability, interaction of TAC with Soluplus ® , and micelle‐forming potency; pharmacokinetic behavior was also evaluated in rats. Tacrolimus in both formulations was in an amorphous state. After storage at 40°C/75% relativity humidity for 4 weeks, there were no significant changes in the crystallinity of TAC between nonaged and aged SMSD/TAC, whereas slight recrystallization was observed in aged ASD/TAC. The results of circular dichroism (CD) and infrared spectroscopic analyses were indicative of the potent drug–polymer interaction in SMSD/TAC, possibly leading to the prevention of recrystallization. Compared with other TAC samples, SMSD/TAC exhibited significant improvement in the dissolution behavior of TAC through the immediate formation of fine micelles. After the oral administration of TAC samples (10 mg TAC/kg) to rats, there was marked enhancement in systemic exposure to TAC with both formulations; in particular, SMSD/TAC achieved an increase in bioavailability ca. 20‐fold higher than crystalline TAC. The SMSD approach might provide an effective dosage form for TAC with enhanced physicochemical stability and oral absorption.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
量子星尘发布了新的文献求助10
1秒前
1秒前
1秒前
33关闭了33文献求助
1秒前
ZZD完成签到 ,获得积分10
1秒前
LW发布了新的文献求助20
1秒前
鲜于飞薇发布了新的文献求助10
1秒前
1秒前
2秒前
SciGPT应助HANK2024采纳,获得10
2秒前
3秒前
研究生发布了新的文献求助10
3秒前
4秒前
4秒前
研友_VZG7GZ应助荷兰香猪采纳,获得10
4秒前
研友_VZG7GZ应助gaterina采纳,获得10
5秒前
万能图书馆应助Dominic采纳,获得10
5秒前
5秒前
ygtrece完成签到,获得积分10
5秒前
SciGPT应助哦耶zyy采纳,获得10
5秒前
ding应助汤飞柏采纳,获得10
5秒前
wade发布了新的文献求助10
6秒前
三新荞发布了新的文献求助10
6秒前
6秒前
专注的白柏完成签到,获得积分10
6秒前
standing发布了新的文献求助10
7秒前
7秒前
8秒前
8秒前
8秒前
徐峰桥发布了新的文献求助10
8秒前
寒冷手链发布了新的文献求助10
8秒前
8秒前
Lucas应助久久久悦采纳,获得10
8秒前
hi发布了新的文献求助10
9秒前
9秒前
10秒前
11秒前
12秒前
djiwisksk66应助凄惨惨戚采纳,获得10
12秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3971125
求助须知:如何正确求助?哪些是违规求助? 3515824
关于积分的说明 11179811
捐赠科研通 3250971
什么是DOI,文献DOI怎么找? 1795610
邀请新用户注册赠送积分活动 875897
科研通“疑难数据库(出版商)”最低求助积分说明 805207