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经口腔颊部给药含普萘洛尔负载纳米颗粒的粘膜粘附混合膜。

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles.

作者信息

Kraisit Pakorn, Limmatvapirat Sontaya, Luangtana-Anan Manee, Sriamornsak Pornsak

机构信息

Division of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Pathumthani 12120, Thailand.

Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.

出版信息

Asian J Pharm Sci. 2018 Jan;13(1):34-43. doi: 10.1016/j.ajps.2017.07.006. Epub 2017 Jul 24.

DOI:10.1016/j.ajps.2017.07.006
PMID:32104376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7032168/
Abstract

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10-20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10-30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

摘要

本研究的目的是制备并表征载有盐酸普萘洛尔(PNL)的纳米颗粒饱和的羟丙基甲基纤维素(HPMC)/聚卡波非(PC)粘膜粘附共混膜,以提高经历首过代谢的药物的渗透性。分别采用离子交联法和流延成膜技术制备纳米颗粒和粘膜粘附共混膜。制备了含载PNL纳米颗粒的HPMC/PC共混膜(PN膜)和不含纳米颗粒的含PNL(80mg/膜)的HPMC/PC共混膜(PP膜)中不同浓度的PNL(70、80、90mg/膜),以测试其溶胀性、粘膜粘附性、释放度、渗透性和物理化学性质。扫描电子显微镜(SEM)图像显示,含80mg/膜PNL的PN膜(PN膜-80)表面部分光滑,有褶皱出现,且有球形、分散良好的纳米颗粒。PN膜-80表面纳米颗粒的尺寸约为100nm,这与使用光散射技术观察到的纳米颗粒尺寸相似。所有PN膜和PP膜的溶胀指数(SI)在第一个时间段(10 - 20分钟)大幅增加,分别在20分钟和30分钟达到溶胀平衡。对于PN膜,PNL的浓度影响粘膜粘附性能,且PNL量增加时趋于更高。在早期时间点(10 - 30分钟)发现所有共混膜制剂均为速释。120分钟后,PN膜-70的释放低于其他PN膜。使用猪颊粘膜进行的渗透研究表明与PP膜相比,膜中包含纳米颗粒增加了PNL的渗透性。因此,颊部给药含载PNL纳米颗粒的粘膜粘附共混膜可能是一种用于经历首过代谢药物的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/a6083339357a/ajps453-fig-0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/b89e3abed67e/ajps453-ga-5001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/5608250cab90/ajps453-fig-0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/2ec64ac7f0fc/ajps453-fig-0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/45b0d5c31bbf/ajps453-fig-0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/d4667e9ad84d/ajps453-fig-0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/e17877d62394/ajps453-fig-0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/a6083339357a/ajps453-fig-0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/b89e3abed67e/ajps453-ga-5001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/5608250cab90/ajps453-fig-0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/2ec64ac7f0fc/ajps453-fig-0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/45b0d5c31bbf/ajps453-fig-0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/d4667e9ad84d/ajps453-fig-0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/e17877d62394/ajps453-fig-0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c55/7032168/a6083339357a/ajps453-fig-0006.jpg

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