盐酸伊伐布雷定单层渗透泵控释片的制备与体外释药行为
Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets
-
摘要: 制备日服1次的盐酸伊伐布雷定（IVB）单层渗透泵控释片。建立了释放度测定方法，单因素考察助悬剂、促渗剂和老化条件等对释药曲线的影响。以片芯中聚氧乙烯（PEO）的用量、控释衣膜中聚乙二醇（PEG）的比例和包衣增重进行3因素3水平的正交设计。最终处方为IVB 16.25 mg，PEO N80 60 mg，羟丙甲基纤维E5 10 mg，乳糖111.75 mg，硬脂酸镁2 mg；包衣液中PEG 15%，醋酸纤维素85%，包衣增重7.5%。体外释药行为表明，药物释放不受环境pH影响，无剂量倾泻风险，释药动力为膜内外渗透压差。IVB渗透泵片能够降低给药次数，提高患者的顺应性，具有临床应用价值。Abstract: In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.
-
Keywords:
- ivabradine /
- osmotic pump /
- preparation /
- in vitro release /
- orthogonal design /
- dose dumping
-
-
[1] . Pharmacol Res，2006，53（5）：424-434. [2] Li JD，Gan T. The clinical application of If current inhibitor ivabradine［J］. J Clin Cardiol（临床心血管病杂志），2020，36（3）：212-214. [3] Electronic Medicines CompendiumUK.Summary of product characteristics of procoralan［EB/OL］.（ 2019-01-25 ）［2021-01-06 ］.https：//www.medicines.org.uk/emc/product/166/smpc .[4] Mullasari A，investigatorsPROFICIENT. Efficacy and safety of ivabradine once-daily prolonged-release versus twice-daily immediate-release formulation in patients with stable chronic heart failure with systolic dysfunction：a randomized，double-blind，phase 3 non-inferiority （PROFICIENT） study［J］. Cardiol Ther，2020，9（2）：505-521. [5] Xu X，Wei YL，Ji W，et al. Pharmacokinetic profile of ivabradine hemisulfate sustained-release tablets administered in Chinese healthy volunteers：an open-label，randomized，single-dose，three-period crossover study［J］. Biomed Chromatogr，2019，33（11）： e4662 .[6] Ma L. Progress in osmotic pump drug delivery system［J］. J China Pharm Univ（中国药科大学学报），2014，45（6）：726-730. [7] Thombre AG，Appel LE，Chidlaw MB，et al. Osmotic drug delivery using swellable-core technology［J］. J Control Release，2004，94（1）：75-89. [8] Malaterre V，Ogorka J，Loggia N，et al. Oral osmotically driven systems：30 years of development and clinical use［J］. Eur J Pharm Biopharm，2009，73（3）：311-323. [9] Zhu L，Qin C，Wu JL，et al. Preparation and in vitro evaluation of pregabalin controlled porosity osmotic pump tablets［J］. J China Pharm Univ（中国药科大学学报），2019，50（1）：53-58. [10] Masciocchi N，Aulisio A，Bertolini G，et al. Disclosing the extensive crystal chemistry of Ivabradine hydrochloride，in its pure and solvated phases［J］. Powder Diffr，2013，28（3）：200-206. [11] Zhou XB，Zhu JR，Liu JY，et al. Crystal structures and properties of two hydrated conglomerate forms of the heart-rate-lowering agent ivabradine hydrochloride［J］. Acta Crystallogr C Struct Chem，2019，75（ Pt 5 ）：545-553.[12] Waterman KC，MacDonald BC，Roy MC. Extrudable core system：development of a single-layer osmotic controlled-release tablet［J］. J Control Release，2009，134（3）：201-206. [13] Smith AP，Moore TW，Westenberger BJ，et al. In vitro dissolution of oral modified-release tablets and capsules in ethanolic media［J］. Int J Pharm，2010，398（1/2）：93-96. [14] Jedinger N，Khinast J，Roblegg E. The design of controlled-release formulations resistant to alcohol-induced dose dumping：a review［J］. Eur J Pharm Biopharm，2014，87（2）：217-226. [15] Costa P，Sousa Lobo JM. Modeling and comparison of dissolution profiles［J］. Eur J Pharm Sci，2001，13（2）：123-133. -
期刊类型引用(3)
1. 李翰铭，尹虹，张金伟，吴燕，邢佳丽，刘雨欣，赵利刚. 盐酸伊伐布雷定缓释微丸的制备工艺及其药动学研究. 沈阳药科大学学报. 2024(07): 875-882 . 
百度学术
2. 梁兆丰. 乙基纤维素对托法替布缓释片释放影响的研究. 今日药学. 2022(10): 747-751 . 百度学术
3. 黄京山，李伟，邵伟. 硫酸羟氯喹控释片的制备和溶出度检测. 山东化工. 2022(23): 77-80 . 百度学术
其他类型引用(1)
计量
- 文章访问数: 196
- HTML全文浏览量: 14
- PDF下载量: 652
- 被引次数: 4
下载:
