不同分子量葡聚糖-地塞米松连接物的体外靶向释药特性不同分子量葡聚糖-地塞米松连接物的体外靶向释药特性

目的筛选具有结肠靶向性的葡聚糖-地塞米松连接物,探讨葡聚糖分子量对连接物体外释药特性的影响。方法将不同分子质量葡聚糖-地塞米松连接物与大鼠胃肠道不同部位内容物稀释液一起孵育,采用反相高效液相色谱法检测地塞米松及地塞米松琥珀酸单酯的释放情况。结果在160 min孵育过程中,胃内容物中未检测到释放的地塞米松及地塞米松琥珀酸单酯;DexD26和DexD50在结肠及盲肠内容物中释放出地塞米松(包括地塞米松琥珀酸单酯)的总量分别是其在小肠近端及小肠远端内容物中释放总量的4.0和3.6倍;DexD2和DexD7.6在结肠及盲肠内容物中释放出地塞米松(包括地塞米松琥珀酸单酯)的总量分别是其在小肠近端及小肠远端内容物中释放总量 的2.0和1.9倍。结论葡聚糖分子质量对连接物的体外释药特性有明显影响,大分子质量葡聚糖-地塞米松连接物具有较大的结肠定位释放潜力。     

地塞米松-葡聚糖酯大鼠体内结肠靶向性

目的：建立地塞米松—葡聚糖酯(DSD)体内含量测定方法，并考察DSD体内结肠靶向性。方法：以Sprague-Daule雄性大鼠为实验动物，灌胃给药法分别给予DSD(实验组)和相当剂量的地塞米松(DEX)(对照组)，高效液相色谱法(HPLC)考察血液、胃、近端小肠、运端小肠、育肠、结肠内容物中DEX分布情况。结果：DSD给药后，血液及胃内容物中游离DEX含量显著低于对照组，盲肠、结肠中药物含量百分率分别为44．35％-83.31％，10．22％-20．52％，远过错高于对照组(盲肠，结肠药物含量百分率分别为0．05％-24．67％，0．79％-3．15％)。结论：DSD经盲肠、结肠中特异性酶类水解后释放出游离DEX，大大降低了DEX的全身吸收，具有良好的结肠靶向性。     

酶依赖结肠靶向地塞米松-葡聚糖酯及其片剂的研究

目的　研制口服结肠定位释放药物的地塞米松 葡聚糖酯及其片剂。方法　通过丁二酸酐搭桥 ,合成地塞米松 葡聚糖酯前体药物 ;紫外光谱、红外光谱、核磁共振谱和质谱法鉴定结构 ;湿法制粒 ,普通压制法制备片剂 ;HPLC法测定体内外地塞米松的含量。结果　合成的地塞米松 葡聚糖酯为目标化合物 ,制得的地塞米松 葡聚糖酯片剂在结肠释放出大部分原药。结论　达到了设计目标 ,有进一步开发研究价值     

酶依赖结肠靶向地塞米松-葡聚糖酯及其片剂的研究

目的　研制口服结肠定位释放药物的地塞米松 葡聚糖酯及其片剂。方法　通过丁二酸酐搭桥,合成地塞米松 葡聚糖酯前体药物;紫外光谱、红外光谱、核磁共振谱和质谱法鉴定结构;湿法制粒,普通压制法制备片剂;HPLC法测定体内外地塞米松的含量。结果　合成的地塞米松葡聚糖酯为目标化合物,制得的地塞米松葡聚糖酯片剂在结肠释放出大部分原药。结论　达到了设计目标,有进一步开发研究价值     

地塞米松当归多糖前体药在大鼠体内的结肠靶向释药研究

目的:探讨以当归多糖为载体的地塞米松前体药在大鼠胃肠道内的转运及活性药物的释放情况。方法:地塞米松及其当归多糖前体药按1.96mg·kg-1(以地塞米松量计)给大鼠灌胃,采用高效液相色谱法检测地塞米松在大鼠胃肠道不同部位的分布及血药浓度变化。结果:地塞米松当归多糖前体药灌胃后,释放出的地塞米松只分布在盲肠和结肠的内容物及粘膜中,在胃和小肠的内容物及粘膜中未检测到地塞米松释放;释放出的地塞米松吸收缓慢,达峰时间(tmax)为7.2h,血浆药物峰浓度(Cmax)为42μg·L-1,曲线下面积(AUC)为334μg·h·L-1。地塞米松灌胃后,药物主要分布在胃、小肠近端及小肠远端的内容物和粘膜中,药物吸收迅速,tmax为2.2h,Cmax为2120μg·L-1,AUC为11875μg·h·L-1。结论:以当归多糖为载体的地塞米松前体药具有良好的结肠定位转释作用,有可能成为一种具有良好应用前景的结肠炎治疗药物。     

吲哚美辛结肠靶向胶囊的制备及体外释药评价

目的 开发一种结肠靶向胶囊,使吲哚美辛达到结肠部位实现靶向释放。方法 以蘸胶工艺制备不溶性半透膜囊体,灌装药物后以果胶片封住囊体,外套上普通胶囊壳后外包肠溶衣,进行体外释放试验。结果 该给药系统在人工胃液中不变形,药物不释放,采用PEG-2 000∶CA为60%的不溶性囊体,包衣增重90%,药物∶NaCl为1∶1制备的胶囊,药物在人工肠液中3 h释放<10%,在人工结肠液中10 h药物释放超过70%,基本释放完全,达到结肠定位释放要求。结论 吲哚美辛结肠靶向胶囊能实现在结肠定位释放药物。     

西米替丁结肠靶向生物粘附释药胶囊的制备

目的：研制西米替丁结肠靶向生物粘附释药胶囊。方法：处方药湿法制粒，干燥后装胶囊，采用紫外分光光度法测定含量。结果：含量测定方法回收率为98.56%，RSD为1.64%。结论：方法准确，可有效地控制该制剂的质量。     

靶向结肠释药系统

靶向结肠释药系统盛杰古丽萍王晓文（中国人民解放军第４７３医院兰州７３００７０）时辰治疗学的新观点即选择在自身组织生物节律周期中适当时刻施以治疗方案，用最小的适宜剂量的药物力求达到高效、低毒、副作用少的目的。心血管病多在清晨发作；哮喘多发生在凌晨３～５...     

前药--一种可靠的口服结肠靶向释药系统

综述了近年来前药的发展状况，并评价了各类前药的特点和发展前景。前药技术作为一种可靠的口服结肠靶向释药系统，不仅能减少药物的口服剂量，降低副作用并且增加了药效。     

奥沙利铂脂质体的制备及体外释药研究

目的：制备一种包封率较高的奥沙利铂脂质体,并考察该脂质体的体外性质。方法采用多种方法制备奥沙利铂脂质体,通过单因素试验和正交试验最终确定脂质体处方。采用高效液相色谱法检测脂质体包封率, ZetaPlus 激光粒度分析仪测定脂质体粒径。同时,采用高效液相色谱法、原子吸收光谱法两种方法考察了该脂质体的体外释放情况。结果与薄膜分散法和 pH 梯度法相比,通过逆相蒸发法制备得到的了奥沙利铂脂质体包封率更高;在此基础上进行的处方筛选试验确定了最优处方工艺为药脂比1∶7.5,胆磷比1∶2,超声功率195 W,超声时间3 min;体外释放试验结果表明,通过高效液相色谱法和原子吸收光谱法测定的奥沙利铂脂质体24 h 的累计释放率分别为25.0%和33.6%。结论通过逆相蒸发法制备得到的奥沙利铂脂质体包封率高,且具有较高的稳定性和一定的缓释作用。     

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.     

Comparative in vitro study of different chitosan-complexing agent conjugates.

In this study we analysed the bioadhesive properties and the enzyme inhibitory effects of different chitosan-complexing agent conjugates. Etylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), respectively, were covalently attached to chitosan by the formation of amide bonds between the primary amino group of the polymer and the carboxylic acid groups of the complexing agents. Whereas almost each primary amino groups of chitosan could be modified by EDTA, DTPA was bound to only 63.8 +/- 5.8% (n = 3; +/- SD) of the amino groups of chitosan. The remaining primary amino groups of the chitosan-DTPA conjugate lead to strongly reduced adhesive properties, with a maximum detachment force of 3.0 +/- 1.3 mN in contrast to the chitosan-EDTA conjugate with 81.7 +/- 9.9 mN in the tensil studies described here (n = 4; +/- SD). However, both polymer conjugates displayed an inhibitory effect towards the zinc-dependent proteases carboxypeptidase A (EC 3.4.17.1) and aminopeptidase N (EC 3.4.11.2). The results of this comparative study should provide substantial knowledge for the development of bioadhesive polymers as auxiliary agents for the peroral administration of peptide and protein drugs.     

羟基喜树碱半固体脂质纳米粒的制备和体外释药特性

目的：制备羟基喜树碱的半固体脂质纳米粒（HCPT-SSLN），初步考察其体外释药规律。方法：采用乳化蒸发-低温固化法制备HCPT-SSLN；用激光粒度仪测定其粒径和ξ电位；考察其混悬液和冻千粉的物理稳定性；用透析法考察其体外释药性质。结果：HCPT-SSLN纳米粒平均粒径为130．5nm，裁药量为2．51％，包封率为79．19％，ξ电位为-33．1mV;室温（25℃）和4℃下放置6个月，纳米粒冻干粉和混悬液外观、粒径及包封率无明显变化；体外释药规律符合Weibull方程lnln[1／（1-Q）]=0．26331nt＋0．0509（R^2=0．9485）。结论：制备的HCPT-SSLN包封率高，稳定性好，大小均匀，体外释药具有缓释特点。     

Ciprofloxacin-loaded bovine serum albumin microspheres: preparation and drug-release in vitro

Ciprofloxacin albumin microspheres were prepared by the spray drying technique, with bovine serum albumin as the natural biodegradable wall material. The spherical microspheres, flowed well, were organic solvent free and in the size range 1 ~ 5 #119 m. The drug release from the microspheres could be retarded by further thermal denaturation. The sustained-release microspheres were suitable for dry powder inhaled lung drug delivery systems.     

Ciprofloxacin-loaded bovine serum albumin microspheres: preparation and drug-release in vitro.

Ciprofloxacin albumin microspheres were prepared by the spray drying technique, with bovine serum albumin as the natural biodegradable wall material. The spherical microspheres, flowed well, were organic solvent free and in the size range 1-5 microm. The drug release from the microspheres could be retarded by further thermal denaturation. The sustained-release microspheres were suitable for dry powder inhaled lung drug delivery systems.     

Characterization and in vitro release of methotrexate from gelatin/methotrexate conjugates formed using different preparation variables

The purpose of this study was to evaluate effects of preparation variables on the composition of gelatin-methotrexate conjugates, and to evaluate their in vitro stability. Conjugation variables of pH, amount of conjugating agent 1-ethyl-3-(diaminopropyl)carbodiimide HCl (EDC), and methotrexate (MTX), with unfractionated gelatin were examined. Conjugate composition was determined spectrophotometrically. The molar ratios of MTX to gelatin in the conjugates ranged from 5.9 to 64.9. Molar ratios increased with molecular weight (MW) of gelatin in the conjugate, but the weight ratio was constant. This common conjugating procedure, however, produces by-product crosslinking and produces a mix of covalent MTX binding to carboxyl and amino groups of the gelatin. For release studies, gelatin was fractionated by size exclusion spectra (SEC) into MW of 21, 91, and 195 kDa prior to conjugation. MTX release from conjugates in dialysis cassettes at 25, 37, and 50 degrees C, in isotonic pH 7.4, buffer over 72 h was assayed by high performance liquid chromatography (HPLC). There was no effect of gelatin MW on MTX release. MTX release was approximately linear and attained 2.3, 7.2, and 13% by 72 h at 25, 37, and 50 degrees C, respectively, for the 91 kDa conjugates. First-order release rate constants were 0.23 x 10(-3), 0.95 x 10(-3), and 1.8 x 10(-3) x h(-1), respectively. The calculated activation energy for MTX release was 15.8 kcal/mol. Rate constants and the activation energy for MTX release are consistent with hydrolysis of a peptide bond. Non-degraded MTX species were found in the release medium at amounts similar to free MTX and were attributed to MTX polymers and MTX/gelatin fragments < 10 kDa.     

High-amylose carboxymethyl starch matrices for oral sustained drug-release: in vitro and in vivo evaluation.

High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation.