洛索洛芬钠缓释微丸的制备与体外释放度研究

摘 要 目的：制备洛索洛芬钠缓释微丸,并考察其体外释药行为。方法: 采用挤出滚圆法制备洛索洛芬钠载药丸芯,再用Eudragit RL 30D和Eudragit RS 30D 进行包衣,制成洛索洛芬钠缓释微丸,并考察缓释微丸的体外释药行为。结果: 以Eudragit RL 30D和Eudragit RS 30D的比例为20∶80作为洛索洛芬钠载药丸芯的缓释包衣材料,包衣增重为20%,增塑剂用量为10%,滑石粉用量为45%时,制备的洛索洛芬钠缓释微丸在12 h内能够平稳释药且释药完全。结论:制备的洛索洛芬钠缓释微丸释药行为较好,有望应用于工业生产。     

洛索洛芬钠缓释微丸的制备

目的:本文拟制备洛索洛芬钠缓释微丸,以期达到降低毒副作用,维持平稳的血药浓度,提高病人顺应性之目的.方法:采用Eudragit(r)NE 30D水分散体作为包衣材料,用流化床悬浮包衣法对洛索洛芬钠微丸进行缓释包衣.结果:以释放度为指标,通过对包衣工艺及处方影响因素的考察,确定了包衣工艺.     

克拉霉素缓释包衣微丸的制备及体外释放度研究

目的制备克拉霉素缓释包衣微丸,并对其体外释放度进行考察。方法采用挤出滚圆技术制备克拉霉素含药微丸。以优化的丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混和水分散体为包衣材料,采用流化床包衣技术,制备缓释包衣微丸。考察自制缓释微丸的体外释药速率,并与市售的克拉霉素缓释胶囊进行比较。结果通过释药行为的评价,得到优化的包衣处方为5∶1的Eudragit NE30D和Eudragit L30D-55混和包衣材料,其体外释放行为在不同的pH溶出介质中与市售制剂产品没有明显差异,体外释药过程符合一级释放模型。结论采用挤出滚圆和流化床技术,以及优化的Eudragit NE30D和Eudragit L30D-55混和水分散体包衣材料,成功制备了克拉霉素缓释包衣微丸。     

离心造粒法制备托拉塞米缓释小丸胶囊及其释放度考察

目的:制备托拉塞米缓释小丸胶囊。方法:采用离心造粒粉末层积法制备托拉塞米小丸,用丙烯酸树脂水分散体包衣,并对包衣小丸的释药特征进行探讨。结果:微晶纤维素(MCC)空白母核32～40目的收率约80.2%,含药素丸20～24目收率约87.6%,使用Eudragit NE30D包衣液,包衣增重10%。托拉塞米缓释胶囊体外释药行为较好地符合Higuchi方程。结论:在优化的工艺条件下可制得表面光滑、圆整度高的托拉塞米缓释小丸。     

盐酸青藤碱缓释微丸的研制

目的制备盐酸青藤碱缓释微丸,并对其体外释药情况进行研究。方法采用离心造粒技术制备微晶纤维素空白丸核和盐酸青藤碱含药丸芯,以聚丙烯酸树脂Eudragit NE 30D为包衣液制成膜控缓释微丸,考察包衣增重、抗粘剂用量等因素对缓释微丸释放度的影响。结果通过单因素考察确定了包衣液处方,所制备的微丸具有明显的缓释特征,体外释药过程符合一级动力学模型。结论用聚丙烯酸树脂Eudragit NE30D作为包衣材料所得缓释微丸符合24 h缓释要求。     

非诺贝特缓释微丸的制备及释放度研究

目的：制备非诺贝特缓释微丸。方法：采用BZJ-360M离心包衣造粒机制备微晶纤维素空白丸核和非诺贝特含药素丸，并在此基础上进行丙烯酸树脂水分散体（Eudragit NE 30D）包衣。用释放度测定法考察影响药物释放的各种因素，对包衣微丸体外释药机制进行研究。结果：包衣材料为Eudragit NE 30D，增重3％时包衣微丸呈现良好的缓释效果，体外释药过程基本符合Higuchi方程：Q=0．436＋30．316t^1/2／（r=0．9997）。结论：成功的制备了非诺贝特缓释微丸。     

厄贝沙坦缓释微丸的制备及体外释药特性的考察

目的制备厄贝沙坦缓释微丸,并对其体外释放度进行考察。方法采用流化床包衣技术,以丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混合水分散体为包衣材料,制备缓释微丸。考察不同释放介质、转速对其体外释药行为的影响。结果优化后的包衣处方为Eudragit NE30D/Eudragit L30D-55的比例为4︰1,抗粘剂和致孔剂的用量分别为聚合物干重的75%及20%,增重10%,熟化24h,释放介质的p H值对微丸释药的影响最明显,其体外释药过程符合一级释药模型。结论成功制备了厄贝沙坦缓释微丸,经考察其释放度符合要求。     

对乙酰氨基酚缓释微丸的制备及释放度研究

目的制备对乙酰氨基酚缓释微丸,考察包衣处方等因素对微丸释放度的影响。方法采用离心-造粒法制备微晶纤维素空白丸核和对乙酰氨基酚微丸,并在此基础上采用甲基丙烯酸树脂(Eudragit RS30D/RL30D)包衣,制备对乙酰氨基酚缓释微丸。采用HPLC法测定对乙酰氨基酚缓释微丸释放度,单因素筛选包衣处方的优化参数。结果以Eudragit RS30D/RL30D比例为15:1(w/w),包衣增重为10%,柠檬酸三乙酯占包衣材料量的25%,滑石粉占包衣材料量的40%为包衣液,制备的对乙酰氨基酚释微丸释药曲线具有较好的缓释特性。结论制备的对乙酰氨基酚缓释微丸具有缓释特性且操作简便、工艺稳定。     

盐酸普拉克索缓释微丸的制备及体外释放度考察

目的:制备盐酸普拉克索缓释微丸。方法:采用挤出-滚圆法制备盐酸普拉克索微丸,再用EudragitRL30D和EudragitRS30D进行包衣,最终制成盐酸普拉克索缓释微丸,并用高效液相色谱法测定药物含量。结果:体外释放度实验显示,制备的盐酸普拉克索缓释微丸在24 h内平稳释放且释药完全。结论:用本方法制备的盐酸普拉克索缓释微丸体外释药平稳,释药规律符合一级释放模型。     

盐酸环丙沙星缓释微丸的研制

目的:制备盐酸环丙沙星缓释微丸(CPSP),并对其体外释药行为进行研究.方法:粉末层积法制备了缓冲型和非缓冲型2种微丸,分别以Eudragit RL 30D,RS 30D水分散体混合物和Eudragit NE 30 D,L 30D55水分散体混合物为包衣材料制备CPSP.分别考察了包衣增重、包衣液中聚合物比例及介质pH对CPSP体外释药行为的影响.结果:选取含有柠檬酸的缓冲型丸芯,包衣增重为7%,RL与RS质量比为1:1.5时,体外释放呈非pH依赖型;包衣增重为4%,Eudragit NE 30D与L 30D55质量比为1:1时释放较理想,体外释放呈显著的pH依赖性.结论:CPSP具有较好的释药性能及良好的缓释效果.     

Preparation and in vitro characterization of piroxicam enteric coated pellets using powder layering technique

The objective of this study was to develop piroxicam enteric coated pellets using nonpareil seeds by powder layering technique to minimize its gastrointestinal adverse effects. Inert seeds were prepared by incorporating sugar, Avicel PH 101 and lactose. The obtained cores were then treated by PVP 10 w/v % solution using centrifugal granulator (CF-granulator) and then coated with micronized piroxicam using HPMC solution (8 w/v %) as binder. The piroxicam pellets were finally coated with different polymers (Eudragit L30D-55, Eudragit L100, Eudragit NE30D, Acryleze, or mixture of Eudragits L30D-55 and NE30D) and plasticizers (triethyl citrate and polyethylene glycol 6000). Results showed that Eudragit L30D-55 with 3% weight gain accompanied with TEC produced suitable enteric coated pellets.     

双氯芬酸钠肠溶微丸型片剂的研制

本文制备了双氯芬酸钠肠溶微丸型片剂。以丙烯酸树脂EudragitNE30D和EudragitL30D-55不同比例的混合物作为衣膜材料，对不同粒径大小的双氯芬酸钠速释丸芯进行不同增重水平的包衣，并与不同压缩特性和用量比例的缓冲微丸混合，压片。所得的双氯芬酸钠肠溶微丸型片剂在人工胃液中2 h内累积释放百分数<10%，在人工肠液中1 h内累积释放百分数为(83±2.42)%。结果表明EudragitNE30D与EudragitL30D-55以一定比例混合制备得到适合压片的肠溶微丸，硬脂酸制备的缓冲微丸可用于微丸型片剂的制备。     

Enteric coated HPMC capsules designed to achieve intestinal targeting.

The enteric coating of HPMC capsules containing paracetamol was investigated. Two enteric polymers, Eudragit L 30 D-55 and Eudragit FS 30 D were studied, which are designed to achieve enteric properties and colonic release, respectively. The capsules were coated in an Accela Cota 10, and, as shown by optical microscopy, resulted in capsules with a uniform coating. Scanning electron microscopy of the surface of the capsules illustrate that, in contrast to gelatin, HPMC has a rough surface, which provides for good adhesion to the coating. Dissolution studies demonstrated that capsules coated with Eudragit L 30 D-55 were gastro resistant for 2 h at pH 1.2 and capsules coated with Eudragit FS 30 D were resistant for a further 1 h at pH 6.8. The product visualisation technique of gamma scintigraphy was used to establish the in vivo disintegration properties of capsules coated with 8 mg cm(-2) Eudragit L 30 D-55 and 6 mg cm(-2) Eudragit FS 30 D. For HPMC units coated with Eudragit L 30 D-55, complete disintegration occurred predominately in the small bowel in an average time of 2.4 h post dose. For HPMC capsules coated with Eudragit FS 30 D, complete disintegration did not occur until the distal small intestine and proximal colon in an average time of 6.9 h post dose.     

对乙酰氨基酚肠溶小丸片的制备工艺研究和质量考察

目的:考察衣膜材料、缓冲小丸的种类以及用量对肠溶型小丸片释药行为的影响。方法:以Eudragit NE30D和FS30D分别与Eudragit L30D-55以不同比例混合后,对含有对乙酰氨基酚的小丸进行包衣。包衣小丸分别与不同的辅料混合后压制成片剂,通过比较压片小丸和未压片小丸释药曲线的相似度(f2)值,来考察包衣膜材的延伸性。同时采用铸膜法制备与包衣处方相同的游离膜,并考察游离膜的机械性能。结果:Eudragit NE30D或Eudragit FS30D与Eudragit L30D-55以2∶1,1∶1和1∶2混合包衣小丸,压成片剂和未压成片的小丸的溶出曲线f2值分别为82,70,65和70,58,41,表明EudragitNE30D和Eudragit FS30D在加入一定量的Eudragit L30D-55后仍可以保护小丸压片时不破裂。采用不同材料制备的缓冲小丸,与包衣小丸混合压片,缓冲材料的种类对片剂的溶出曲线影响不大,主要是通过影响片剂的硬度和崩解时限而影响片剂的质量。结论:Eudragit NE30D和Eudragit FS30D均有着良好的延展性,添加Eudragit L30D-55后延展性变差...     

盐酸青藤碱肠溶缓释微丸的制备

目的：制备盐酸青藤碱肠溶缓释微丸。方法：分别以Eudragit NE30D为缓释膜材，HPMC E5为隔离层膜材，Eudragit L30D-55为肠溶层膜材，采用流化床包衣法制备盐酸青藤碱肠溶缓释微丸，并考察缓释层、隔离层和肠溶层包衣增重对药物释放的影响。结果：制备的肠溶缓释微丸在人工胃液中释放度<10%，人工肠液中缓慢释放8 h。结论：该制备工艺简单易行，重现性好，有望应用于工业化生产。     

麝香保心pH依赖型梯度释药微丸的研究

目的制备麝香保心pH依赖型梯度释药微丸并进行体内外考察。方法分别以HPMC,Eudragit L-30D-55和Eudragit L100-Eudragit S100(1∶5)为包衣材料制备pH依赖型梯度释药微丸,并进行体外释放度、胃肠道转运和体内药代动力学研究。结果冰片和人参总皂苷体外释放度的f₂值为79.6,3种包衣微丸分别在胃、十二指肠和空回肠部崩解,由3种微丸组成的缓释胶囊中冰片的T_max与原丸剂相近,而C_max明显降低,相对生物利用度为96%。结论 缓释胶囊中的冰片和人参总皂苷在体外可同步缓释,在体内具有pH依赖性崩解溶散的特征,冰片作为指标性成分具有梯度缓释的药代动力学特点。     

Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.     

Design and study of ibuprofen disintegrating sustained-release tablets comprising coated pellets.

One challenge in tableting of sustained-release multiparticulates is maintaining the desired drug release after compaction. The aim of this study was to design sustained-release ibuprofen tablets which upon oral ingestion rapidly disintegrate into sustained-release pellets in which the integrity of the pellet core and/or coat is preserved. First free films composed of Eudragit RS 30D and RL 30D in 4:1 ratio and containing different levels of triethyl citrate (TEC) were prepared and tested to optimize the plasticizer level. Cured Eudragit based pellets with 60% ibuprofen loading which in our previous study showed proper mechanical properties for compression were coated with Eudragit RS 30D/RL 30D (4:1) containing 20% triethyl citrate at different coating levels. The mechanical properties of the coated pellets were tested. Polymer coated pellets were compacted into tablets either alone or with a blend of excipients comprising Avicel, PEG 4000, cross-linked PVP. A 3(2) full factorial design was used to optimize the filler blend composition. Effects of pellet to filler ratio, compression force and granulation of filler on tablet characteristics were investigated. Results of mechanical test showed that the coating of cured pellets had no significant effect on yield point and elastic modulus of the pellets. In the case of 5% coating level sustained release of ibuprofen over a period of 24h was achieved. The results obtained from tableting procedure showed that by selecting suitable filler blend (60% Avicel, 10% cross-linked PVP and 30% PEG 4000), compression force, and granulation of filler it was possible to prepare sustained-release tablets containing high ratio of coated pellets (even 80%) with desirable strength, disintegration time, and drug release rate. It was observed that compression force, pellet to filler ratio, composition of filler blend and granulation of fillers had no effect on drug release rate from compacted pellets but had significant influence on tablet strength, friability, and disintegration time. SEM graphs and in vitro release profiles for compacted pellets showed no apparent damage to the coated pellets as a result of the compaction process.     

Influence of an enteric polymer on drug release rates of theophylline from pellets coated with Eudragit RS 30D

The purpose of this research study was to investigate the influence of an enteric polymer on the drug release properties of theophylline pellets coated with Eudragit RS 30D. Theophylline pellets were coated with aqueous colloidal dispersions of Eudragit RS 30D containing various amounts of Eudragit L 100-55. The effect of storage conditions on the release of drug from coated pellets was determined as a function of the pH of the dissolution medium. The results from the dissolution study showed significant changes in the dissolution rate of theophylline from pellets coated with Eudragit RS 30D when cured at 40 degrees C for 4 days. No change in the drug release rate was observed when Eudragit L100-55 was present in the Eudragit RS 30D dispersion. Increasing the ratio of Eudragit L100-55 to Eudragit RS 30D resulted in faster drug release rates from the coated pellets. An increase in the pH of the dissolution medium was found to enhance drug release from the pellets coated with Eudragit RS 30D containing Eudragit L 100-55. Theophylline pellets when coated with Eudragit RS 30D containing the enteric polymer Eudragit L100-55 demonstrated no aging effects when stored at elevated temperatures. The overcoating of the pellets with Eudragit RD 100 did not affect the drug release profiles and prevented the particles from agglomerating during curing and storage.