Optimization of tamsulosin hydrochloride controlled release pellets coated with Surelease and neutralized HPMCP

This study was to optimize the coating level in the development of controlled release pellets coated with Surelease and neutralized hydroxypropyl methylcellulose phthalate (HPMCP) by a computer optimization technique based on a response surface methodology utilizing polynomial equation. A full factorial 3(2) design was used for the optimization procedure with coating level (X(1)) and HPMCP content (X(2)) as the independent variables. The drug release percent at 2, 3 and 5 h were the target responses, which were restricted to 12-39% (Y(1)), 44-70% (Y(2)) and 70-100% (Y(3)), respectively. The quadratic model was well fitted to the data, and the resulting equation was used to predict the responses in the optimal region. It was shown that the optimized coating formulation was achieved at the ratio of 3:1 (Surelease: neutralized HPMCP) with 20% coating level. The optimized formulation showed release profiles and responses, which were close to predicted responses. Therefore, a full factorial 3(2) design and optimization technique can be successfully used in the development of optimized coating formulations based on Surelease and neutralized HPMCP to achieve a controlled release drug delivery system containing tamsulosin hydrochloride.     

盐酸坦洛新胃漂浮缓释小丸的制备与体外释放

目的研制盐酸坦洛新胃漂浮缓释小丸并考察其体外释放特性。方法采用液中干燥法制备胃漂浮小丸,以收率、圆整度、平均粒径、释放度和漂浮性为指标,考察处方工艺因素对小丸性能的影响。结果圆整度较好,小丸收率质量分数在75%以上,随搅拌速度增加粒径减小,体外缓释8 h,漂浮效果较好。结论盐酸坦洛新胃漂浮缓释小丸具有较好的漂浮及缓释性能,是一种较理想的口服缓释制剂。     

盐酸坦索罗辛缓释微丸胶囊的制备及处方工艺考察

目的:制备盐酸坦索罗辛缓释微丸胶囊。方法:采用苏丽丝、雅克宜、欧巴代II作为包衣材料,用流化床底喷溶液上药法制备载药微丸,并进行缓释包衣。结果:以释放度为指标,通过对包衣工艺及处方影响因素的考察,确定了包衣处方工艺。结论:本研究处方工艺简便,重现性良好,可能适合工业化生产。     

Some problems for dosage form based on questionnaire surveying compliance in patients taking tamsulosin hydrochloride

After the dosage form of tamsulosin hydrochloride was changed from a capsule to on orally disintegrating tablet (ODT, Harnal D), we often received patient complaints and noted an increase in noncompliance with medication regimens. The change in dosage form appeared to cause poor compliance by patients who had become accustomed to the light pink/white capsule over many years. Therefore, we carried out a questionnaire survey of patients taking the ODT form to determine the effects of changing the dosage form and the usefulness of the ODT. Most (92%) of respondents took the ODT with water. In addition, 16% missed taking the medicine after the change in dosage form. ODT is a dosage form that is easy to take for patient with dysphagia, or those on restricted water intake. However, it appears that elderly men and patients with visual disorders cannot distinguish the ODT from other medicines and this affects patient compliance. In conclusion, all pharmaceutical companies should consider the design of medications in terms of coloration, indications, or shape in anticipation of the aging society in future, so that patients can distinguish them. Furthermore, sufficient pharmaceutical care is needed to improve both compliance and safety management for the elderly.     

盐酸二甲双胍缓释微丸的制备及体外释放度考察

目的:制备盐酸二甲双胍(metformin hydrochloride,MH)缓释微丸,并考察其体外释药行为。方法:通过离心造粒法制得MH微丸,以乙基纤维素水分散体(Surelease),丙烯酸树脂水分散体(EudragitNE30D,RS30D)作为膜控释包衣材料,通过流化床包衣制备MH缓释微丸,并考察不同包衣材料、包衣增重、固化时间、释放介质对释放度的影响。结果:离心造粒制得微丸圆整度好,有一定强度,适合包衣,Surelease包衣增重11%时所得的缓释微丸在12 h具有明显的缓释效果,不受释放介质的影响,为零级释放,且12 h释放可以达到85%以上。释放机制主要是通过无孔膜扩散作用。结论:通过离心造粒并用Surelease包衣的MH缓释微丸缓释效果明显,且为零级释放。     

化学药物口服缓控释制剂体内外相关性研究

《口服缓控释制剂药学研究技术指导原则》中多处提到了体内外相关性,文中试图通过对体内外相关性(IVIVC)的定义、创建、评价和应用等方面的介绍,对IVIVC可行性的评估以及IVIVC与生物豁免和释放度质量标准的关系的讨论,帮助研发者理解该指导原则的相关内容。     

盐酸安非他酮缓释片处方筛选及体外释放评价

目的 筛选盐酸安非他酮缓释片的处方及缓释层包衣增重。方法 分别以盐酸安非他酮缓释片片芯的物理参数及缓释片的释放曲线为考察指标,通过调整片芯处方中填充剂、润滑剂、助流剂及缓释层包衣增重,确定了盐酸安非他酮缓释片的处方。结果 当片芯处方中采用微晶纤维素KG802、山嵛酸甘油酯和胶体二氧化硅时可获得片面较好的片芯,当处方中缓释层增重为4.0%时制得的缓释片分别在0.1 N盐酸溶液、pH 4.5醋酸盐和pH 6.8磷酸盐溶出介质中的释放曲线与原研制剂释放行为相似。结论 筛选的盐酸安非他酮缓释片处方合理。     

Design and evaluation of novel barrier layer technologies for controlling venlafaxine hydrochloride release from tablet dosage form

Abstract

Context: Venlafaxine Hydrochloride (VH) is a highly soluble and highly permeable antidepressant compound. Thus controlling VH release from tablet dosage form over a prolonged period is a challenge.

Objective: The objective of this work was to study the effect of various barrier layer formulation compositions, its orientations and manufacturing technology on release profile of highly soluble VH.

Materials and methods: Different barrier compositions and orientations were established on the same extended release formulations of VH using compression as well as film coating technologies. Barrier effectiveness in reducing the VH release was verified through in vitro dissolution studies.

Results and discussion: The “belly band” portion of the tablets was successfully oriented in different ways to develop bilayer as well as trilayer tablets. The compression technology had substantially reduced the VH release up to 16% in various compositions and orientation as compared to core tablet. The film coating technology had reduced the VH release up to 14% effectively; thereby shifting the dissolution curve to downside.

Conclusion: The explored “belly band” portion of the tablets had reduced the VH release substantially. These innovatively created different barrier orientation technologies hold the great promise of commercialization in future.     

Stability-indicative HPLC determination of donepezil hydrochloride in tablet dosage form

Asimple, selective, precise and stability-indicative high-performance liquid chromatography (HPLC) method of analysis of donepezil hydrochloride in tablet dosage form has been developed and validated. The drug undergoes degradation under acidic, basic, peroxide, photochemical and thermal conditions. The method has been statistically validated for linearity, accuracy, precision, limit of detection, limit of quantitation, solution stability, and selectivity according to ICH recommendations. Due to its simplicity and accuracy, the method can be used for routine drug quality control.     

Validated RP-HPLC and TLC methods for simultaneous estimation of tamsulosin hydrochloride and finasteride in combined dosage forms

Reversed-phase high-performance liquid chromatography (RP-HPLC) and thin-layer chromatography (TLC) methods have been developed and validated for simultaneous estimation of tamsulosin hydrochloride and finasteride in bulk drug and in combined dosage forms. RP-HPLC separation was achieved on a Phenomenex C18 column using methanol/0.02 mol L-1 ammonium acetate buffer/triethylamine (79.9 + 20 + 0.1, V/V/V) (pH 9.2) as mobile phase. TLC separation was achieved on an aluminium-backed layer of silica gel 60 F254 using toluene/methanol/triethylamine (9 + 1.5 + 1, V/V/V) as eluent. Quantification was achieved with photodiode array (PDA) detection at 235 nm over the concentration range 0.5-16 and 1-50 μg mL-1 with mean recovery of 99.8 ± 0.9 and 100.0 ± 0.8% for tamsulosin hydrochloride and finasteride, respectively, by the RP-HPLC method. Quantification was achieved with UV detection at 270 nm over the concentration range 100-2000 ng per spot and 250-5000 ng per spot with mean recovery of 98.9 ± 0.9 and 99.6 ± 0.7 % for tamsulosin hydrochloride and finasteride, respectively, by the TLC method. Both methods are simple, precise, accurate and sensitive and are applicable to the simultaneous determination of tamsulosin hydrochloride and finasteride in bulk drug and in combined dosage forms.     

乙醇摄入对盐酸苯环壬酯控释片释放行为的影响

目的：考察乙醇摄入对盐酸苯环壬酯控释片释放行为的影响。方法：测定盐酸苯环壬酯控释片中盐酸苯环壬酯原料在不同浓度乙醇磷酸盐缓冲液（pH3.0）中溶解度;关键辅料WSR-HM、WSR-LM在不同浓度乙醇磷酸盐缓冲液（pH3.0）中的黏度;以0%、5%、20%、30%、40%乙醇磷酸盐缓冲液（pH3.0）为释放介质,考察并比较盐酸苯环壬酯控释片的体外累积释放度,并采用扫描电镜观察释放介质中不同浓度的乙醇对盐酸苯环壬酯控释片薄膜衣的表面结构和释药孔的影响。据此分析乙醇影响盐酸苯环壬酯控释片体外释放的原因。结果：盐酸苯环壬酯在pH3.0磷酸盐缓冲液和5%、20%、30%、40%乙醇磷酸盐缓冲液（pH3.0）中的溶解度分别为39.6,47.3,84.7,171.4,235.4 mg·mL^-1;WSR-HM、WSR-LM的黏度随释放介质中乙醇浓度的增加而下降;盐酸苯环壬酯控释片在pH 3.0磷酸盐缓冲液和5%乙醇磷酸盐缓冲液释放介质中的释放曲线相似（相似因子f₂=74）,但在20%、30%、40%乙醇磷酸盐缓冲液（pH3.0）释放介质中的释放度有显著变化;盐酸苯环壬酯控释片完全释放后,残留释药孔的直径分别为552,600,630,718,815 μm。结论：5%乙醇对盐酸苯环壬酯控释片的释放影响最小,而随着乙醇浓度的增加,乙醇通过改变盐酸苯环壬酯溶解度、WSR-HM及WSR-LM黏度和溶胀程度从而对盐酸苯环壬酯控释片的释放产生影响,并且乙醇浓度越大,体外释放越快。     

The influence of chitosan and sodium alginate and formulation variables on the formation and drug release from pellets prepared by extrusion/spheronisation

The influence of the incorporation of two oppositely charged hydrophilic natural polymers, chitosan and sodium alginate, alone and in combination, on the ability of formulations containing a model drug (paracetamol) to form spherical pellets by the process of extrusion/spheronisation and the properties of the pellets, has been undertaken. A statistically experimental design was employed to allow the major factors which determined the properties of the pellets, to be identified. A standardised procedure was used to prepare the pellets with a ram producing the extrudate for spheronisation. Statistical analysis of the results indicated that the formulation variables of the type and level of the polymer, the proportion of the model drug, and the proportion of the microcrystalline cellulose influenced (a) the quantity of liquid binder required to produce a good formulation (narrow size range and high value for the shape factor indicating sphericity), (b) the steady-state extrusion force, (c) the pellet perimeter, (d) the apparent pellet density and (e) the porosity of the pellets. The median size of the pellets of the "good formulation" could only be related to the chitosan and sodium alginate content of the formulations. The proportion of the drug, chitosan and sodium alginate content of the formulation significantly influenced the in vitro dissolution of the model drug (paracetamol). The drug release mechanism differed with the formulation variables, although if the pellets remained intact during the dissolution test, diffusion was the controlling mechanism. There was no significant advantage to be gained by using a mixture of the two polymers in terms of retarding drug release.     

Formulation and evaluation of a gastroretentive dosage form of labetalol hydrochloride

Labetalol hydrochloride (LBT), 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyl]-benzamide, a non-selective α, β-adrenoceptor antagonist is used in the treatment of hypertension. It shows variable bioavailability ranging from 10–80% which may be attributed to its minimum solubility in pH range 6 to 10, the pH conditions prevailing at the major site of absorption i.e. small intestine. Also due to its half life of 3 to 6 hrs it is administered twice daily. In the present work non-effervescent sustained release gastroretentive floating tablets of labetalol hydrochloride have been developed using various grades of HPMC and Poloxamer M127 as wetting agent. The tablets were evaluated for in vitro drug release, floating time, floating lag time, swelling studies etc. The tablets formulated with HPMC K4M CR and HPMC K15M CR along with Poloxamer showed negligible floating lag time with a total floating time over 12 hrs with complete release. Formulation was optimized using Stat-Ease Design Expert 7.1 software. Optimized batch was evaluated for the effect of change of osmolarity and pH on drug release, floating and swelling behaviour.     

浅析丙戊酸钠在癫痫病中的应用及剂型选择

丙戊酸钠作为常用一线抗癫痫药,目前在临床的应用较为广泛。本文对丙戊酸钠在癫痫治疗中的应用、作用机理、毒副作用以及丙戊酸钠的剂型发展作一介绍。     

载阿霉素海藻酸钠纳米粒的制备及体外释药行为研究

目的以海藻酸钠(sodium alginate,ALG)为材料,制备载阿霉素海藻酸钠纳米粒(doxorubicin loading nanoparticles,DOX-ALG-NPs),并对其载药、释药特性进行研究。方法采用微乳-离子交联法制备空白海藻酸钠纳米粒(ALG-NPs),以吸附法载药制备阿霉素海藻酸钠纳米粒(DOX-ALG-NPs)。采用效应面法对ALG-NPs的处方进行优化,并考察ALG-NPs悬液浓度、药载比、孵育时间及孵育温度对ALG-NPs载药性能的影响。对DOX-ALG-NPs的基本性质及体外释药行为进行考察。结果成功制备了粒径为(262.0±4.5)nm的ALG-NPs及粒径为(159.8±8.1)nm、包封率及载药量分别为(94.2±0.5)%和(19.05±0.085)%的DOX-ALG-NPs。与原料药DOX相比,DOX-ALG-NPs在生理盐水与PBS(pH=7.4)中均呈现明显的缓释作用,在生理盐水和PBS中2 h与5 h时分别释放药物(38.1±1.5)%与(55.5±1.1)%、(40.0±1.8)%与(48.1±2.5)%,24 h时分别释放(73.1±3.2)%、(60.3±3.4)%。结论所制备的DOX-ALG-NPs形态圆整,粒径小且分布均匀,包封率及载药量较高,具有缓释性能,有望用作抗癌药物传递系统。     

The influence of pellet shape and surface properties on the drug release from uncoated and coated pellets

The crystallisation of amorphous salbutamol sulphate prepared by spray drying was monitored using a humidity controlled microbalance (Dynamic Vapour Sorption apparatus, Surface Measurement Systems) combined with a near-infrared probe. Amorphous salbutamol sulphate was prepared by spray drying from a solution in water. The particles were then analysed using scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, isothermal microcalorimetry and water vapour sorption analysis combined with near-infrared spectroscopy (NIR). Isothermal microcalorimetry and water vapour sorption combined with NIR spectroscopy were able to detect the transition from the amorphous to crystalline state. However while the isothermal microcalorimeter showed only a classic crystallisation exotherm when the material was exposed at 75% RH, the DVS-NIR results at the same humidity highlighted a more complex process. When exposed at 75% RH, the uptake of water was followed by crystallisation that was detected using NIR. The expulsion of water after crystallisation was very slow and at a constant rate whether the material was exposed to 75 or 0% RH. The NIR and DVS studies indicated that the material had crystallised very soon after exposure to high RH. The water that was expelled during crystallisation was not displaced from the particles and remained associated with the particles for many days. This study showed that the use of gravimetric analysis together with NIR spectroscopy provided valuable information on the dynamics of the crystallisation of salbutamol sulphate. The retention of water within recently crystallised salbutamol is potentially important to the behaviour of dosage forms containing the amorphous (or partially amorphous) form of this drug.     

海藻酸钠骨架材料中药物释放的影响因素

目的以海藻酸钠为亲水骨架材料，考察药物从海藻酸钠骨架片中释放的体外影响因素。方法以茶碱为模型药物，采用直接压片法制备了茶碱海藻酸钠亲水骨架片，通过对骨架片膨胀性、吸水性以及溶蚀性的考察，研究了影响药物从海藻酸钠骨架材料中释放的体外因素。结果茶碱海藻酸钠骨架片的释药速率和释药机理与骨架片中海藻酸钠粘度、释放介质pH值、离子强度以及转速均有关。结论海藻酸钠能有效地控制骨架片中药物的释放，是一种优良的亲水骨架材料。