Delivery of Prazosin Hydrochloride from Osmotic Pump System Prepared by Coating the Core Tablet with an Indentation

The preparation of an osmotic pump tablet was simplified by elimination of laser drilling using prazosin hydrochloride as the model drug. The osmotic pump system was obtained by coating the indented core tablet compressed by the punch with a needle. A multiple regression equation was achieved with the experimental data of core tablet formulations, and then the formulation was optimized. The influences of the indentation size of the core tablet, environmental media, and agitation rate on drug release profile were investigated. The optimal osmotic pump tablet was found to deliver prazosin hydrochloride at an approximately constant rate up to 24 hr, and independent on both release media and agitation rate. Indentation size of core tablet hardly affected drug release in the range of 0.80–1.15 mm. The method that is simplified by elimination of laser drilling may be promising for preparation of an osmotic pump tablet.     

Preparation of monolithic osmotic pump system by coating the indented core tablet.

A method for the preparation of monolithic osmotic pump tablet was obtained by coating the indented core tablet compressed by the punch with a needle. Atenolol was used as the model drug, sodium chloride as osmotic agent and polyethylene oxide as suspending agent. Ethyl cellulose was employed as semipermeable membrane containing polyethylene glycol 400 as plasticizer for controlling membrane permeability. The formulation of atenolol osmotic pump tablet was optimized by orthogonal design and evaluated by similarity factor (f2). The optimal formulation was evaluated in various release media and agitation rates. Indentation size of core tablet hardly affected drug release in the range of (1.00-1.14) mm. The optimal osmotic tablet was found to be able to deliver atenolol at an approximately constant rate up to 24h, independent of both release media and agitation rate. The method that is simplified by coating the indented core tablet with the elimination of laser drilling may be promising in the field of the preparation of osmotic pump tablet.     

夹芯渗透泵片用于水不溶性药物的控制释放夹芯渗透泵片用于水不溶性药物的控制释放

目的研究夹芯渗透泵片用于水不溶性药物的24 h控制释放。方法以硝苯吡啶为模型药物,制备夹芯渗透泵片,研究处方、释药孔径等因素对夹芯渗透泵片释药规律的影响,并考察包衣的机械性质。结果药物层中聚氧乙烯和膨胀层中氯化钾对释药的正面影响最大。在0.50～1.40 mm,孔径对释药影响不大。醋酸纤维素包衣牢固可靠,能承受0.34～2.85 MPa的内压。结论夹芯渗透泵片能24 h匀速释放水不溶性药物。环境介质和搅拌对释药的影响不大。与市售双层渗透泵片相比,夹芯渗透泵片免去了打孔前的药物层辨认过程,制备过程简化。     

Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet

In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require laser drilling to form the drug delivery orifice is described. The bilayer-core consisted of two layers: (a) push layer and (b) drug layer, and was made with a modified upper tablet punch, which produced an indentation at the center of the drug layer surface. The indented tablets were coated by using a conventional pan-coating process. Although the bottom of the indentation could be coated, the side face of the indentation was scarcely sprayed by the coating solution and this part of the tablet remained at least partly uncoated leaving an aperture from which drug release could occur. Nifedipine was selected as the model drug. Sodium chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and croscarmellose sodium as expanding agent. The indented core tablet was coated by ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for controlling the membrane permeability. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f(2)). It was found that the optimal OPT was able to deliver nifedipine at an approximate zero-order up to 24 h, independent on both release media and agitation rates. The preparation of bilayer-core OPT was simplified by coating the indented core tablet, by which sophisticated technology of the drug layer identification and laser drilling could be eliminated. It might be promising in the field of preparation of bilayer-core OPT.     

阿替洛尔单层芯渗透泵片的制备

目的以阿替洛尔为模型药物研究单层芯渗透泵片简化的制备方法，并进行处方优化。方法用自行设计的带针冲头压制带孔单层片芯， 以乙基纤维素为膜材包衣制备渗透泵片， 采用相似因子为指标筛选处方。结果 单层芯渗透泵片的片芯处方、包衣膜组成及厚度是影响释药的主要因素。在1.00～1.14 mm，片芯孔径对释药影响不大。结论本制备方法可免去激光打孔过程，制得的阿替洛尔单层芯渗透泵片能24 h匀速释药。     

Solubility-modulated monolithic osmotic pump tablet for atenolol delivery.

A method for the preparation of monolithic osmotic pump tablet was obtained by modulating atenolol solubility with acid. Tartaric acid was used as solubility promoter, sodium chloride as osmotic agent and polyvinyl pyrrolidone as retardant agent. Ethyl cellulose was employed as semipermeable membrane containing polyethylene glycol 400 as plasticizer. The formulation of atenolol monolithic osmotic pump tablet was optimized by orthogonal design and evaluated by similarity factor (f(2)). The optimal monolithic osmotic pump tablet was found to be able to deliver atenolol at the rate of approximate zero-order up to 24h, independent of release media and agitation rate. The approach of solubility-modulated by acid-alkali reaction might be used for the preparation of osmotic pump tablet of other poorly water-soluble drugs with alkaline or acid groups.     

复方二甲双胍/格列吡嗪单室渗透泵片的释药机理

目的在以前的实验中研制了复方二甲双胍/格列吡嗪单室渗透泵片,但是其释药机理没有阐明。方法在本文中,主要考察了可能影响药物释放的三个限速因素(半透膜,片心和释药孔)。结果研究发现单位时间内透进渗透泵的水量同二甲双胍的释放速率基本相当,但远小于片心的溶出速率;孔径从0·4到0·8毫米对药物释放无显著影响;片心的渗透压主要由二甲双胍产生。结论从渗透泵系统的数学模型来看,主要限速步骤在于单位时间透过半透膜的水量,不是片心溶出速率和溶液从小孔的释放速率,片心的溶出速率同溶液从小孔的释放速率相等,因此渗透泵系统表现出零极释放。     

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。     

单层芯渗透泵片用于水不溶性药物的控制释放单层芯渗透泵片用于水不溶性药物的控制释放

渗透泵片是一种理想的口服控释制剂。国外已将其商品化并依靠它取得了很好的经济效益 ,国内从 2 0世纪 80年代开始研究 ,但是 ,在过渡到工业化时遇到困难[1] 。高速、准确地辨识双层芯渗透泵片的药物层是确保正确打释药孔的必须而又困难的环节 ,也是大规模工业化生产的主要障碍。本文[2 ] 研制的夹芯渗透泵片免去了药物层辨识过程。单层芯渗透泵片既免去药物层辨识过程 ,又简化片芯制备 ,更容易实现工业化生产。本工作研究片芯处方变量对单层芯渗透泵片释药的影响规律。材料与方法药品与仪器、硝苯吡啶定量法和体外释放度测定法等参照文献 [2 ]。单层芯渗透泵片制备　片芯成分在研钵中研磨混匀过 80目筛后 ,直接压成直径 8mm的单层芯片。以 2 5 %醋酸纤维素 (辅以 35 %的聚乙二醇和 5 %的三醋酸甘油酯 )丙酮溶液作包衣液 ,将片芯置于包衣锅内 ,吹入热空气 ,包衣层至 170 μm厚。将包衣片在 6 0℃干燥 2 4h。然后 ,在包衣片两侧各制备一个直径 0 5mm的释药孔。结果与讨论1　聚氧乙烯分子量对释药的影响聚氧乙烯 (PEO)分子质量为 30 0 0 0 0时释药最快 ,10 0 0 0 0和 90...     

盐酸青藤碱口服渗透泵控释片的制备及释药影响因素考察

目的制备了盐酸青藤碱口服渗透泵控释片 ,考察该制剂的释药影响因素及释药机理。方法利用正交设计优化处方 ,根据不同时间累积释放度考察药物的释放情况。结果制备了盐酸青藤碱口服渗透泵控释片 ,体外释药速度较市售缓释片缓慢、平稳。结论本制剂遵从以渗透压差为释药动力的释药模式 ,16h内呈现良好的零级释放特征 ,此后 ,随渗透泵内药量的减少 ,释放速度略下降     

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。     

Microporous bilayer osmotic tablet for colon-specific delivery

Microporous bilayer osmotic tablet bearing dicyclomine hydrochloride and diclofenac potassium was developed using a new oral drug delivery system for colon targeting. The tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan-coating process. The developed microporous bilayer osmotic pump tablet (OPT) did not require laser drilling to form the drug delivery orifice. The colon-specific biodegradation of pectin could form in situ delivery pores for drug release. The effect of formulation variables like inclusion of osmogen, amount of HPMC and NaCMC in core, amount of pore former in semipermeable membrane was studied. Scanning electron microscopic photographs showed formation of in situ delivery pores after predetermined time of coming in contact with dissolution medium. The number of pores was dependent on the amount of the pore former in the semipermeable membrane. In vitro dissolution results indicated that system showed acid-resistant, timed release and was able to deliver drug at an approximate zero order up to 24 h. The developed tablets could be effectively used for colon-specific drug delivery to treat IBS.     

微孔渗透泵片的药物传递机制

口服渗透泵片以渗透压为驱动力，以零级释放动力学为释药特征，能在一定的时间内以恒定的释药速率释放药物，释药速率一般不受释放介质pH、搅拌速度及胃肠蠕动、食物等因素的影响，是理想的一种口服控释制剂。     

盐酸普鲁卡因胺渗透泵片剂的研究

本文研究了盐酸普鲁卡因胺(PA·HCl)渗透泵片的处方组成、制备工艺、体外溶出;建立了PA·HCl的紫外双波长分光光度法及血清和唾液中PA及其活性代谢物N-乙酰普鲁卡因胺(NAPA)共存下的高效液相色谱法,体内PA实验数据按双室模型,用电子计算机处理求得药动学参数。药动学—药效学数据显示血药浓度和唾药浓度均与药效变化规律相关。     

岩白菜素包合物渗透泵片体外释药机制研究

目的探索岩白菜素β-环糊精(β-CD)包合物渗透泵片的体外释药机制。方法通过考察可能影响药物释放的3个因素(包衣膜、片芯和释药孔),探讨其主要的释药动力和零级释药机制。结果水透膜的速率远小于片芯中药物的溶出速率及岩白菜素渗透泵片的释药速率;扩散与溶蚀机制对渗透泵片释药有影响。结论岩白菜素包合物渗透泵片的释药受多种机制共同影响;片芯的渗透压主要由岩白菜素包合物产生;体外释药的限速步骤为水透膜速率,因此渗透泵系统呈现出零级释放。     

Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride

The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.     

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。     

原料药粒径对盐酸普萘洛尔渗透泵片释药行为的影响

目的:研究原料药粒径等对盐酸普萘洛尔渗透泵片释药行为的影响。方法:取不同批号盐酸普萘洛尔及同批号重结晶前、后的原料药均按相同处方制备成渗透泵片,考察药物体外释放情况及释药24h后衣膜形态;并对上述不同原料药的粒径分别以光学显微镜和激光粒度分析仪进行证实。结果:以原料药粒径较小的渗透泵片释放完毕后衣膜变形,且不能维持零级释放,原料药粒径较大的渗透泵片结果与之相反。不同原料药经仪器证实粒径确有差异。结论:原料药的粒径可影响制备的渗透泵片的释放行为,提示性状稳定的原料药的合理选择在制剂过程中不可忽视。     

乌拉地尔渗透泵片的制备

目的:制备体外24h恒速释药的乌拉地尔渗透泵片。方法:以氯化钠和高、低分子量(4×106、2×105)的聚氧化乙烯(PEO)组成片芯,醋酸纤维素和聚乙二醇400为包衣液,制备乌拉地尔渗透泵片;采用相似因子(f2)为指标筛选片芯处方,并考察了其释药机制。结果:与理想释药曲线最接近的片芯处方组成为乌拉地尔60mg,氯化钠190mg,PEO(Mr4×106)90mg,PEO(Mr2×105)90mg,药物24h维持零级释放。结论:本渗透泵片制备方法简便,且零级释药特征明显。     

同离子效应对盐酸普萘洛尔渗透泵片释药速率的影响

目的:研究同离子效应对盐酸普萘洛尔渗透泵片中药物释放速率的影响。方法:采用释放度测定Ⅱ法(USP28版), 应用不同pH值、不同氯离子浓度的释放介质,考察药物累积释放度,得出其释放曲线,并结合不同介质的性质进行比较。结果:盐酸普萘洛尔渗透泵片在不同pH的介质中释放速率基本相同,而在不同氯离子浓度的介质中释放速率存在较大差异。结论:由于同离子效应,释放介质及片芯中的氯离子对盐酸普萘洛尔从渗透泵片中的释放存在较大的影响。