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.     

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.     

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。     

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.     

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。     

硫酸特布他林脉冲控释片的制备与释放机理研究硫酸特布他林脉冲控释片的制备与释放机理研究

目的制备硫酸特布他林双层包衣脉冲片，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。方法粉末直接压片法制备含渗透活性物质的片芯，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，并研究脉冲片的吸水动力学和膨胀行为。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、溶胀和渗透泵原理。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。     

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。     

Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.     

Preparation of monolithic osmotic tablet of quercetin loaded by solid dispersion

The objective of this study was to prepare monolithic osmotic tablet of quercetin for controlled drug release. Quercetin-PVP solid dispersion was prepared to enhance its solubility and dissolution rate. Solid dispersion, suspending agents, osmotic agents and other conventional excipients were used as tablet core composition and cellulose acetate (CA) with plasticizer as release controlling membrane. Different formulation variables, the amounts of PEO (polyethylene oxide), NaCl, plasticizer, and coating weight gain were optimized to gain the optimum formulation. The mechanism of drug release from monolithic osmotic tablet was also discussed. The optimal monolithic osmotic pump tablet could deliver quercetin at the rate of approximate zero-order up to 12 h, and the cumulative release was 90.74%. The developed monolithic osmotic system for quercetin loaded by solid dispersion was found to be a promising approach for controlled release of poorly-water soluble drug candidates.     

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...     

元胡止痛渗透泵片的制备和处方优化

目的:采用双层渗透泵技术制备元胡止痛渗透泵片并进行处方优化。方法:测定各处方在2,4,6,8,10,12 h时的累积释放度,以f₂相似因子作为释药曲线相似性的判断标准,采用单因素实验分别考察片芯处方和包衣处方对元胡止痛渗透泵片体外释药行为的影响。结果:含药层聚氧乙烯分子量和用量、促渗剂种类和用量、包衣增重可显著影响元胡止痛渗透泵片体外释药;助推层聚氧乙烯、促渗剂的用量对其体外释药无显著影响。优化处方制备的元胡止痛渗透泵片的释药方程为:Q=7.094t-4.188,r=0.9950,符合零级模型,且体外释药行为不受释放条件等因素影响。结论:采用双层渗透泵技术研制的元胡止痛渗透泵片制备工艺可行,缓释特征显著,可用于元胡止痛方的剂型现代化。     

Drug tablet thickness estimations using air-coupled acoustics

A non-contact/non-destructive acoustic technique for predicting the coating layer thickness of a drug tablet is presented. Quality of tablet coatings can play a major role in the effectiveness of drug delivery. Many pharmaceutical tablets consist of a tablet core and a coated outer cover. Variations in the tablet coating can be indicative of various process problems and, therefore, is of a concern for quality assurance. In the current non-contact measurement system, an air-coupled excitation and laser interferometric detection for predicting the coating layer thickness of a drug tablet is introduced. Drug tablets with different coating thicknesses are vibrated via an acoustic field generated by an air-coupled transducer in a frequency range sufficiently high to excite their several vibrational modes. The tablet surface vibrational responses are acquired at a number of measurement points by a laser interferometer in a non-contact manner. An iterative computational procedure, based on the FE method and Newton's method, was developed and demonstrated to extract the coating layer thicknesses of the tablets from a subset of the measured resonance frequencies.     

Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose: effect of coating conditions

An orally applicable nifedipine-loaded core tablets was coated using high viscosity grade HPMC (100,000 cps) in ethanol/water cosolvent. The release of coated tablet was evaluated using USP paddle method in 900 ml of simulated gastric fluid (pH 1.2) for 2 h followed by intestinal fluid (pH 6.8) for 10 h. The surface morphologies using scanning electron microscope and photo-images using digital camera of coated tablet during the release test were also visualized, respectively. The viscosity of hydro-alcoholic HPMC solution largely decreased as the amount of ethanol increased. There was no significant difference in viscosity among plasticizers used. The distinct and continuous coated layer was observed using scanning electron microscope. However, the surface morphologies were highly dependent on HPMC concentration and ratio of coating solvents. The higher ratio of ethanol/water gave a longer lag time prior to drug release. Lag time also increased as a function of the coating levels based on weight gains due to increased thickness of coated layer. Lag time is inversely correlated with HPMC concentration in ethanol/water (5:1) cosolvent. As the HPMC concentration slightly decreased from 3.8 to 3.2% in hydroalcoholic coating solution, a large increase of lag time was observed. As the swelling (mixing) time of high viscosity grade HPMC in ethanol/water cosolvent increased from 1 to 5 h, the release rate was decreased due to enough plasticization of polymer. Based on photo-imaging analysis, the coated tablet was initially swelled and gelled without erosion and disintegration over 5 h. The disintegration of the coated tablet was occurred approximately 7 h after dissolution, resulting in pulsed release of drug. The high viscosity grade HPMC can be applicable for polymeric coating after careful selection of solvent systems. The release behavior and lag time could be controlled by coating conditions such as HPMC concentration, ethanol/water ratio as a coating solvent, coating level and swelling (mixing) time of coating solution. The current time-controlled release tablet coated with high viscosity grade HPMC with a designated lag time followed by a rapid release may provide an alternative to site specific or colonic delivery of drugs. In addition, the release behavior can be matched with body's circadian rhythm pattern in chronotherapy.     

Monolithic Osmotic Tablets for Controlled Delivery of Antihypertensive Drug

An oral monolithic osmotically controlled delivery system for nifedipine using asymmetric membrane technology was developed and evaluated. Unlike conventional osmotic systems, which require laser drilling, this system releases the drug in a controlled manner from asymmetric membrane coated core tablets. Asymmetric membrane is formed by dry process with phase inversion technology process using cellulose acetate as the coating material. Higher water influx of this membrane aids in delivery of nifedipine, which is highly water insoluble with low osmotic pressure. The porous structure of the membrane was confirmed by scanning electron microscopy. Influence of different osmotic agents on drug release was evaluated. In vitro release studies showed that as concentration of osmotic agents was increased, the drug release was also enhanced. Drug release from the developed monolithic system was independent of external agitation and pH of dissolution media. Comparative in vitro release data was obtained using different types of coating membranes like controlled porosity membrane and dense coating membrane with mechanically drilled orifice. Osmotic pressure generated in the system was determined using freezing point osmometer. The osmotic pressure developed was found to be linearly proportional to time and concentration of osmotic agent.     

Applicability of (SBE)7m-beta-CD in controlled-porosity osmotic pump tablets (OPTs)

The purpose of this study was to investigate the general application of a controlled-porosity osmotic pump tablet (OPT) utilizing (SBE)7m-beta-CD as both a solubilizer and an osmotic agent for drugs with varying physical properties. OPTs utilizing (SBE)7m-beta-CD were prepared for five poorly soluble and two highly water-soluble drugs. The Japanese Pharmacopoeia dissolution method was used to study the drug and (SBE)7m-beta-CD release from the OPTs. The drug concentration in the OPT core after the OPT was placed in the release medium for two hours was assayed gravimetrically and by HPLC. An appropriate composition ratio (ACR) of (SBE)7m-beta-CD to drug at which drug release from the OPT was complete and pH-independent within the physiological pH range of the GI tract was determined for each drug. The ACR values correlate to the drug concentration in the OPT core when the OPTs were placed in the release medium for two hours. The release profiles of prednisolone (a poorly water-soluble drug) and sodium chloride (a water-soluble compound) from the OPTs were almost the same as that of (SBE)7m-beta-CD. Also, the release rate of each drug per unit membrane surface area from the OPTs was similar, regardless of the differences in drug solubility. The present results confirmed that (SBE)7m-beta-CD serves as both a solubility modulator and as an osmotic pumping agent for OPTs, from which the release rate of both water-soluble and poorly water-soluble drugs can be controlled.     

奥沙西罗包衣控释片的制备及其质量评价

目的制备奥沙西罗包衣控释片,考察处方组成和工艺因素对制剂质量及体外释药行为的影响,并分析其释药机制。方法以乙基纤维素(EC-45cP)为骨架材料、乙基纤维素(EC-10cP)为成膜材料、聚乙二醇6000(PEG6000)为增塑剂,采用滚转包衣锅包衣,药物作为致孔剂控制药物释放,考察处方因素,片芯制备和包衣工艺等对制剂质量及体外释放行为的影响。结果片芯骨架材料用量、致孔剂用量、增塑剂用量、包衣厚度等因素对药物释放有明显影响。制剂体外释药行为符合零级动力学方程。结论薄膜包衣法制得奥沙西罗控释片,调整处方组成可获得12 h平稳释药的制剂。     

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.     

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.     

盐酸昂丹司琼渗透泵片的制备与体外释放

目的制备盐酸昂丹司琼渗透泵型控释片剂(OND-OPT)并考察体外释药特性。方法以锅包衣法制备OND-OPT。通过释放度试验筛选处方并考察OND-OPT的释放特性；通过均匀设计试验建立持续释药时间与衣膜厚度、衣膜中PEG含量和释药孔孔径的关系；考察OND-OPT的释药机制。结果释药孔朝向对不含HPMC的制剂释药有明显影响，而对含HPMC的制剂释药无影响。持续释药时间与衣膜厚度和衣膜中PEG含量有关，与释药孔孔径无显著关系。OND-OPT主要以渗透泵机制释放药物。结论通过调节衣膜厚度和衣膜中PEG含量，OND-OPT可以实现理想的药物控制释放。