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.     

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.     

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.     

盐酸普萘洛尔药物树脂渗透泵控释制剂的设计

目的:制备以盐酸普萘洛尔药物树脂复合物为含药片芯的渗透泵控释片。方法:通过单因素考察,以2f相似因子法筛选适宜的辅料。结果:聚氧乙烯PEO(N80)和NaCl被选为主要辅料。结论:药物树脂复合物可压性极差,需要一种黏度大、可压性好的辅料使之成型。通过验证PEO满足实验要求。离子交换树脂所载药物需要一定离子强度才能被交换释放,NaCl作为离子型促渗剂,与非离子型促渗剂相比能更快、更多地释放药物。此外,NaC l还具有补充渗透泵外环境中用于交换药物所消耗的离子的作用,预防患者由于长期服用诱发体内电解质紊乱。     

Gastrointestinal transit of an osmotic tablet drug delivery system

The gastrointestinal transit of a radiolabelled osmotic tablet drug delivery system has been monitored in groups of young and elderly healthy subjects, using gamma scintigraphy. The gastric emptying and small intestinal transit times were similar for both groups of subjects. The units were observed to move through the gastrointestinal tract at about the same rate as the released contents, arriving at the caecum on average 7 h after dosing. The data suggest that tablet adhesion to the mucosal surface is unlikely to be the mechanism responsible for the side effects reported for the indomethacin formulation Osmosin.     

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.     

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.     

普萘洛尔药物树脂渗透泵在犬体内的药动学及体内外相关性评价

目的对制备的普萘洛尔药物树脂渗透泵片在Beagle犬体内药动学进行研究并对体内外相关性做出评价。方法对6条Beagle犬进行双周期双交叉实验,利用高效液相色谱法测定不同时间Beagle犬血浆中的药物浓度,用DAS 2.0统计软件计算有关药动学参数。以紫外分光光度计测定普萘洛尔树脂渗透泵控释片的体外释放浓度,Wanger-Nelson法计算体内吸收百分数,进行体内外相关性评价。结果药物树脂渗透泵体外释放具有2 h时滞,2～14 h恒速释药,24 h累积释放90%以上。体内吸收5 h后达到最低有效浓度,普萘洛尔树脂渗透泵片与普通片主要药动学参数分别为t_(max)(11.0±s 1.1)和(3.0±0.6)h;t_(1/2) (6±4)和(3.2±0.6)h;c_(max)(128±11)和(750±55)μg·L~(-1);AUC_(0-∞)(2583±508)和(2 708±386)μg·h·L~(-1),且体内外相关性较好。结论普萘洛尔树脂渗透泵片的时滞现象为时辰给药提供了可能,且血药浓度平稳,与普通片相比可较长时间保持有效血药浓度。     

口服渗透泵制剂的研究进展

通过查阅国内外相关文献,对口服渗透泵制剂的释药机制、种类及影响其药物释放的因素进行综述。口服渗透泵的发展日趋成熟,为了更好地满足患者的用药需求,应开发适合工业化生产的渗透泵制剂。     

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。     

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...     

吲达帕胺微孔渗透泵片的设计与制备

目的 设计并制备吲达帕胺微孔渗透泵片剂.方法通过单因素考察和正交试验设计,以释放度为指标筛选优化处方.结果 以微晶纤维素(MCC)、可压性淀粉、乳糖、氯化钠、羟丙基甲基纤维素(HPMC) K4M、十二烷基硫酸钠为片芯材料;以醋酸纤维素、聚乙二醇(PEG) 400、邻苯二甲酸二乙酯(DEP)的丙酮溶液为包衣液,制备了...     

渗透泵药物传递系统制备技术研究进展

渗透泵药物传递系统由于能够平稳的释放药物,且释药不易受药物的理化性质、病人生理因素及摄入食物的影响,日益受到药学工作者的关注.目前,已经上市销售的渗透泵片数目对比10年前增长了近1倍.该文简述了渗透泵药物传递系统的结构分类、详细介绍了口服渗透泵制备技术近年来的研究进展.     

Controlled porosity osmotic pump for the delivery of flurbiprofen

Controlled porosity osmotic pump contains water-soluble additives in the coating membrane, which in contact with aqueous environment dissolves and results in formation of micro porous membrane. The resulting membrane is substantially permeable to both water and dissolved drug. The drug release from this type of system is independent of pH and follows zero order kinetics. In the present investigation, effort has been made to study release mechanism of drug having low water solubility by means of controlled porosity osmotic pump. The capsule membrane was prepared by phase inversion technique. The phase inversion was carried by dipping the stainless steel mould in a 15% solution of cellulose acetate containing varying amounts of pore-forming agent, glycerol (50% to 70% w/w), followed by quenching in an aqueous solution (10% w/v glycerol), which resulted in the formation of the asymmetric membrane. The delivery orifices so formed were confirmed by release of an encapsulated dye from the capsule and scanning electron microscope (SEM). The drug selected for this study, Flurbiprofen, has low water solubility and hence is unable to create osmotic pressure to cause drug release. To enhance the solubility and its osmotic pressure, this study was conducted with a solubility enhancer sodium lauryl sulfate (SLS). The quantity of SLS was predetermined by conducting a solubility study of flurbiprofen with SLS. Release rate studies revealed that less than 10% of drug was released from the system without SLS, while about 75% release was observed from systems containing SLS. The release rate increased as the concentration of pore forming agent increased.     

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。     

丹酚酸B渗透泵控释片的制备

目的:研究丹酚酸B渗透泵控释片的处方及工艺,并对影响累积释放度的各种因素进行考察。方法:以体外累积释放度作为评价指标,采用单因素考察确定最优处方。结果:促渗剂的种类及剂量、聚乙二醇的种类及剂量、包衣增重对累积释放度有显著影响,片芯硬度、释药孔径、释放介质及转速对累积释放度无显著影响。结论:丹酚酸B渗透泵控释片在12 h内呈现良好的零级释放(r=0.993 1),药物累积释放比较完全(>92%)。     

Controlled porosity osmotic pump system for the delivery of diclofenac sodium: in-vitro and in-vivo evaluation

Abstract

The objective of this study was to develop controlled porosity osmotic pump (CPOP) tablets of diclofenac sodium (DS). The influence of different cores (polymers and osmogens) and coats (thickness and porosigen content) on DS release were studied. Results revealed that decreasing HPMC viscosity grade from 4000cp (K4M) to 15cp (E15) increased DS release. While increasing the tablet coat thickness decreased DS release. The presence of osmogen increased DS release in the following rank: mannitol?>?lactose?>?avicel. There was a direct relationship between increasing PEG-400 in the coating solution and the amount of drug released in all formulations studied, except in one condition. A comparative bioavailability study using a selected CPOP formulation (T) versus the innovator product (R) revealed that CPOP tablet maintained a less fluctuated DS plasma concentration for up to 24?h with a detected mean C_max of 836.8?±?142.4 and 445.0?±?81.0?ng/mL for R and T, respectively. There were no statistically significant differences between R and T, concerning AUC_0?24 and AUC_0?∞. Moreover, the appearance of the multi-peak phenomenon, which is frequently observed with DS absorption, was found in only 25% of volunteers in case of T versus 75% in case of R.     

Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

Elementary osmotic pump (EOP) is a unique extended release (ER) drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA), respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30) and sodium lauryl sulfate (SLS). The plasticizer amount and molecular weight (MW) together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM) thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.     

格列齐特推拉式渗透泵的制备

目的:优化格列齐特推拉式渗透泵的处方,并对影响释放度的各种因素进行考察。方法:以紫外分光光度法对格列齐特推拉式渗透泵的体外释放度曲线进行测定,应用f2因子法为手段,对不同处方中药物释放曲线的相似性进行评价,对处方进行优化。结果:包衣增重、片心硬度及助推层中氯化钠的用量对药物的释放曲线有显著影响,释药孔径大小、转速以及打片时的填料顺序对释放曲线无显著性影响。结论:应用推拉式渗透泵系成功制备了格列齐特渗透泵,控释时间达12 h。     

双氯芬酸钠药物树脂复合物的体外释放特性

目的:制备双氯芬酸钠药物树脂复合物,对其体外释药动力学进行考察。方法:采用不同交联度的离子交换树脂以静态法制备双氯芬酸钠药物树脂复合物并对双氯芬酸钠药物树脂复合物释放的影响因素进行考察。结果:随着树脂交联度的减小,树脂对双氯芬酸钠的载药速率变快,载药量增加。体外释药动力学研究表明,双氯芬酸钠药物树脂的释药速率随着温度的升高和溶出介质中离子强度的增大而加快;而且与树脂本身性质也有关,释药速率随着树脂交联度和粒径的减小而增大;双氯芬酸钠药物树脂的释放为pH依赖型。结论:双氯芬酸钠药物树脂的释药速率与释放温度、溶出介质的离子强度和pH值及树脂交联度和粒径有关。