硝苯地平双层控释片的制备与体外释放

目的:采用渗透泵技术,制备硝苯地平控释片,并进行体外释放研究。方法:采用单因素筛选处方,分别考察含药层高分子聚氧乙烯(PEO)相对分子质量、含药层渗透压活性物质、助推层中高分子PEO相对分子质量、助推层的含量、压力、包衣膜厚度和释药孔孔径等因素对释放度的影响。结果:通过系列研究,结果表明,衣膜的完整性、能否释放药物以及释药速度的快慢主要受含药层中高分子PEO的相对分子质量、渗透压活性物质和助推层中高分子PEO相对分子质量、含药层和助推层体积比及压力、孔径、半透膜等因素的影响。结论:自制的硝苯地平双层渗透泵控释片在体外释药条件下释药稳定,在3～14h内零级特征明显(r=0.9995)、平均释药量约为8%/h、衣膜完整。     

吲达帕胺微孔渗透泵片的制备与体外释药机制研究

目的制备吲达帕胺微孔渗透泵片剂并研究其体外释药机制。方法通过外观观察,测定不同衣膜、片芯、介质等条件变化时的体外释放度,考察其释药机制。结果吲达帕胺微孔渗透泵片体外释药行为符合零级释药模型;不同衣膜、片芯和渗透压介质对药物释放有显著影响;释放介质的pH值、溶出方法和转速对药物释放无显著影响。结论该片剂的释药动力主要为衣膜内外的渗透压差,药物在渗透压驱动下经微孔释药。     

盐酸维拉帕米脉冲控释片的制备及体外释放度研究

制备了渗透泵控释的盐酸维拉帕米片芯，依次包时滞衣层和控释衣层制得脉冲控释片。考察了时滞衣层增重和控释衣膜处方及增重对药物释放时滞和释放速率的影响，同时比较了制品在不同释放介质中的释药行为。结果显示，时滞衣层增重与脉冲控释片的释放时滞呈正相关（r=0．9959），但对药物的释放速率影响较小；控释衣膜中的致孔剂种类和用量及控释衣层增重对体外释药均有不同程度的影响；释药孔的数量对药物释放影响较小，但释药孔的减少可能会导致衣膜膨胀变形。脉冲控释片的体外释放不受介质pH的影响。     

西罗莫司单层高分子渗透泵控释片的制备及其体外释放特性研究

目的:制备西罗莫司单层高分子渗透泵控释片并考察其体外释放特性。方法:通过对片芯组成中的释药载体聚氧乙烯(PEO)的分子量、用量,促渗剂种类及氯化钠(NaCl)用量,包衣液中的聚乙二醇400(PEG400)用量,衣膜增重等设计单因素试验进行初步筛选,在此基础上以NaCl用量、衣膜增重、PEG400用量为因素,以释药方程的相关系数r为评价指标设计正交试验,考察并优化制剂处方及工艺,同时对其体外释放特性进行评价。结果:以PEO(Mw20000)30mg、NaCl70mg为片芯辅料,PEG4000.14g为包衣材料,衣膜增重12mg时制得的片剂最优,其零级释放特征显著,r=0.9954。结论:该制剂制备工艺简单,在体外可近恒速缓慢释放药物。     

盐酸二甲双胍渗透泵控释片的制备及体外释放度考察

目的研究盐酸二甲双胍渗透泵控释片的制备工艺及体外释药的影响因素。方法通过单因素考察和正交试验,优化制备工艺。结果盐酸二甲双胍渗透泵控释片的体外释药符合零级释放规律,释药速率受PEG种类、PEG用量、包衣膜重量影响较大,在一定范围内,释药孔大小、片芯硬度、溶出介质pH值和桨转速对其影响较小。结论盐酸二甲双胍渗透泵控释片工艺稳定,能够达到9h明显的恒速释药。     

丙烯酸树脂RS100和丙烯酸树脂RL100混合包衣制备法莫替丁渗透泵控释片

目的制备难溶性药物法莫替丁渗透泵型控释片,并考察其释药的影响因素,探讨药物释药规律。方法从渗透促进剂用量、阿拉伯胶用量、衣膜性质、释药孔径和转速等5个因素考察对释药的影响。结果制备了难溶性药物法莫替丁渗透泵型控释片,氯化钠、阿拉伯树脂胶、衣膜厚度是影响释药的主要因素。结论法莫替丁渗透泵型控释片工艺稳定,能够达到12 h明显的恒速释药。     

包衣处方对盐酸文拉法辛微孔渗透泵型控释片体外释药的影响

目的考察包衣处方对盐酸文拉法辛口服微孔渗透泵控释片体外释药的影响,并优选最佳包衣处方。方法考察聚乙二醇400(PEG400)的用量、包衣增量、邻苯二甲酸二丁酯(DBP)的种类和用量4个因素对释放的影响,并通过正交设计优化包衣处方。结果盐酸文拉法辛微孔渗透泵控释片的体外释药符合零级释放规律,释药速率受致孔剂、增塑剂、衣膜厚度的影响均较大。结论通过对包衣处方的优化,盐酸文拉法辛口服微孔渗透泵控释片能够恒速释药。     

度米芬渗透泵片的研制

目的:制备度米芬渗透泵片,并考察、分析其释药机制。方法:以均匀设计法优化包衣工艺,测定不同处方制剂累积释药百分率,研究渗透泵片的制剂学特征及释药机制。结果:致孔剂聚乙二醇-400用量和包衣膜厚度对药物释放均有影响。优化包衣工艺条件为聚乙二醇-400用量12%、包衣膜厚度10mg。喷雾速度、温度、转速对释药行为无影响。结论:改变度米芬渗透泵片包衣成分的组成,制剂可持续12h释药;该制剂释药机理包括扩散和渗透泵原理。     

盐酸维拉帕米口服渗透泵制剂释药特性的研究

以盐酸维拉帕米为模型药物，制备了口服渗透泵片，通过考察渗透泵片体外释药各过程的速率，研究口服渗透泵制剂释药的基本过程及其特性，结果表明盐酸维拉帕米口服渗透泵制剂的释药过程主要包括四个步骤，其中体外释药速率与由水渗透过膜过程所控制的药物释放速率接近，从而说明水渗透过膜是控速步骤。     

盐酸沙格雷酯渗透泵控释片的研制

目的：制备盐酸沙格雷酯渗透泵控释片。方法：采用单冲压片工艺，醋酸纤维素为包衣材料，制备渗透泵片，考察不同的渗透促进剂，包衣增重，释药孔大小对累积释药百分率的影响，并用高效液相法测定药物的含量和释放度。结果：采用柠檬酸为渗透促进剂，包衣处方为醋酸纤维素2％，聚乙二醇400用量8％、包衣增重7％，释药孔径0．5mm，得到渗透泵片在2h释药为9．5％，6h释药46．1％，12h释药96．01％。结论：通过调节促渗剂、包衣增重和释药孔径，盐酸沙格雷酯可以实现理想的药物控制释放。     

磷酸川芎嗪微孔渗透泵片的研制及释药机制研究

目的:制备磷酸川芎嗪微孔渗透泵片,并进行处方优化和释药机制考察。方法:利用单因素考察和正交试验设计,优化筛选出最佳处方;测定不同处方制剂累积释药百分率;并对其释药机制进行探讨。结果:包衣膜中致孔剂聚乙二醇400用量、片芯羟丙甲基纤维素含量、增塑剂邻苯二甲酸二丁酯用量、包衣增重为影响药物释放的4个重要因素。最优处方为聚乙二醇400用量10%,羟丙甲基纤维素用量5%,增塑剂10%,包衣增重12mg,制得微孔渗透泵片在12h内呈现零级控释释放特征(r=0.99981),累积释放率为94.2%,批间重现性良好,不受胃肠道环境影响;释药机制包括渗透泵机制和扩散机制,以渗透泵机制为主。结论:该微孔渗透泵片处方及制备工艺简单有效,12h零级释放特征显著,重现性好,可为工业生产提供理论依据。     

罗红霉素渗透泵型控释片处方工艺研究

目的：探讨罗红霉素渗透泵型控释片的处方工艺。方法：以罗红霉素（RXM）为模型药物,通过测定药物的释放度,考察促渗透剂、渗透聚合物种类及其用量、片芯硬度、释药孔径、包衣膜组成、包衣膜厚度对药物释放的影响。结果：PVP和增塑剂用量、包衣膜厚度和释药孔径对渗透泵型控释片的药物释放具有显著影响,一定范围内片芯硬度对药物释放的影响不明显。结论：选用500mg／mL的蔗糖作为渗透促进剂;200mg／mL的聚维酮-K30（PVP）为促渗透聚合物;包衣膜选用200mg／mL的PEG-6000。     

Factors Affecting the Release of Nifedipine from a Swellable Elementary Osmotic Pump

Oral osmotic devices including an elementary osmotic pump (EOP) are efficient systems for the delivery of drugs with high/moderately water-solublility. In this study we designed a new type of EOP for the efficient delivery of poorly water-soluble and practically insoluble drugs. In this system, called swellable elementary osmotic pump (SEOP), drug is released from the delivery orifice in the form of a very fine dispersion of drug in gel which is ready for dissolution and absorption. Factors affecting the release of drug from the SEOP containing a poorly water-soluble drug, nifedipine, were explored extensively. To this end, effect of swelling and wetting agents, orifice size, concentration of osmotic agent, and hydrophobic plasticizer were investigated. Interestingly, in the absence or low concentration of a hydrophobic plasticizer (caster oil), the osmotic devices did not retain their integrity in dissolution media. Caster oil in concentration of > 1% was necessary for tablets to retain their integrity during dissolution process. A zero-order release kinetics for nifedipine was achieved following the effective optimization of the concentrations of swelling agent, osmotic agent, wetting agent, and also size of orifice and membrane thickness in SEOP. The zero-order release lasted for 10 hr at pH 6.8 dissolution medium. The designed SEOP is suggested as an efficient controlled delivery system for oral delivery of a poorly water soluble drug such as nifedipine.     

Factors affecting the release of nifedipine from a swellable elementary osmotic pump

Oral osmotic devices including an elementary osmotic pump (EOP) are efficient systems for the delivery of drugs with high/moderately water-solubility. In this study we designed a new type of EOP for the efficient delivery of poorly water-soluble and practically insoluble drugs. In this system, called swellable elementary osmotic pump (SEOP), drug is released from the delivery orifice in the form of a very fine dispersion of drug in gel which is ready for dissolution and absorption. Factors affecting the release of drug from the SEOP containing a poorly water-soluble drug, nifedipine, were explored extensively. To this end, effect of swelling and wetting agents, orifice size, concentration of osmotic agent, and hydrophobic plasticizer were investigated. Interestingly, in the absence or low concentration of a hydrophobic plasticizer (caster oil), the osmotic devices did not retain their integrity in dissolution media. Caster oil in concentration of > 1% was necessary for tablets to retain their integrity during dissolution process. A zero-order release kinetics for nifedipine was achieved following the effective optimization of the concentrations of swelling agent, osmotic agent, wetting agent, and also size of orifice and membrane thickness in SEOP. The zero-order release lasted for 10 hr at pH 6.8 dissolution medium. The designed SEOP is suggested as an efficient controlled delivery system for oral delivery of a poorly water soluble drug such as nifedipine.     

尼莫地平渗透泵型控释片的研制及释药影响因素考察

目的制备中剂量难溶性药物尼莫地平单室渗透泵型控释片 ,并考察其释药机理及影响释药因素 ,探讨药物释药规律。方法单因素考察影响释药的因素。结果制备了中剂量难溶性药物尼莫地平单室渗透泵型控释片 ;氯化钠、阿拉伯树脂胶、衣膜厚度及增塑剂的用量是影响释药的主要因素。结论尼莫地平单室渗透泵型控释片工艺稳定 ,能够达到 12h明显的恒速释药     

Novel two-step release system for the traditional Chinese medicine compound Danshen

A novel two-step release system for the traditional Chinese medicine compound Danshen was developed by combining an effervescent osmotic pump tablet (EOPT) and a pulsed-released tablet (PT) of compound Danshen into one hard capsule. The EOPT of Danshen was prepared with sodium chloride, mannitol, hydroxypropylmethylcellulose (HPMC), and sodium bicarbonate as osmotic agents. The osmotic pressure from EOPT was greatly enhanced by carbon dioxide generated from the reaction between sodium bicarbonate and acidic components from Danshen. It was shown that the tested Danshen components could be completely released from the prepared EOPT following a zero-order release for up to 12 h. The PT of compound Danshen was a three-layer coated tablet composed of organic acid and osmotic agents. Eudragit RL, HPMC and the mixture of EC and Eudragit RS, RL were the major constituents of the separation layer, swelling layer and controlling release membrane, respectively. The swelling test of the PT indicated that swelling is a prerequisite for drug release from this PT device. In addition, the swelling behavior further suggested the drug release mechanism of PT involves diffusion, the osmotic pumping effect, and organic acid-induced effect, among which the osmotic pumping effect was the most important. Moreover, there was no significant difference among the five active constituents in their release profiles from the final combined two-step release system of compound Danshen.     

生物粘附性达那唑缓释栓剂的处方筛选与体外释放度考察

目的 :生物粘附性达那唑栓剂的处方筛选 ,并考察其体外释放规律。方法 :以羟丙甲基纤维素 (HPMC)为缓释材料 ,将等量聚乙二醇6000(PEG6000)和聚乙二醇600(PEG600)以熔融法制备含不同HPMC量的缓释栓剂 ,考察释放度与HPMC用量之间的关系。结果 :随着HPMC用量增加 ,栓剂释药减慢 ,当HPMC与PEG的比例为1∶6 5时 ,栓剂中药物在体外12h内缓慢释放 ,符合一级释放规律。结论 :生物粘附性骨架材料HPMC能延缓达那唑从栓剂中释放 ,当HPMC与PEG的比例为1∶6 5时栓剂能达到设计要求。     

硫酸沙丁胺醇脉冲控释片的研制

目的:制备硫酸沙丁胺醇双层包衣脉冲片,考察处方及释放条件对体外释药行为的影响,解析其释放机理.方法:混合粉末直接压片,滚转包衣锅法分别包溶胀层和控释衣层.通过测定释放度研究脉冲片的制剂学特征.结果:双层包衣片以脉冲形式释放,释药时滞随控释衣层厚度增加而延长,释药速度减小;渗透压活性物质和溶胀层可提高快速释放期的释药速率.溶出介质pH值和搅拌速度对释药行为无影响.释药机理包括扩散、溶胀和渗透泵机理.结论:调整控释衣膜厚度和组成可获得理想的脉冲释药行为,满足时辰治疗的要求.本给药系统设计可推广应用于水溶性药物的脉冲给药系统研究.