硝苯地平-海藻酸钠骨架缓释片的制备及处方工艺优化

目的：研制硝苯地平-海藻酸钠骨架缓释片并优化处方工艺。方法：以海藻酸钠为缓释骨架材料,乳糖为填充剂,硬脂酸镁为润滑剂,乙醇为黏合剂,湿法制粒并制备硝苯地平骨架缓释片。在处方单因素考察的基础上,选择对缓释片释放行为影响较大的3个处方因素——海藻酸钠用量、磷酸氢钙用量和海藻酸钠黏度,以累积释放度为指标,利用正交实验设计L9（34）对缓释片处方进行优化。考察制备的硝苯地平骨架缓释片的释放机制。将自制缓释片的体外释放行为和大鼠体内药动学与市售缓释片进行比较。结果：在3个处方因素中,磷酸氢钙用量对硝苯地平-海藻酸钠骨架缓释片的体外释放度影响最大,最佳处方组成为45%海藻酸钠、20%磷酸氢钙和黏度为105m Pa·s的海藻酸钠。处方优化的硝苯地平骨架缓释片体外释放行为符合一级动力学方程,属于Baker-Lonsdale球形扩散机制。与市售产品相比,自制缓释片的缓释效果更好;其经口给予大鼠后,硝苯地平的tmax明显延长,药物作用时间延长及生物利用度提高。结论：自制的硝苯地平-海藻酸钠骨架缓释片具有明显的缓释效果,并优于市售产品。     

卡托普利混合骨架片的处方筛选及优化

目的:研制混合骨架的卡托普利缓释片.方法:采用两因素六水平的均匀设计法筛选混合骨架片的优化处方,其中,两因素为缓释骨架材料HPMC K4M和蜡质888(Compritol 888);六水平指这两种缓释材料6种不同的用量.结果:最终优化处方中缓释材料HPMC K4M用量为20%,Compritol 888用量为30%.结论:用优化的处方,工艺制备的3批卡托普利缓释片体外释放良好,质量稳定.     

阿奇霉素壳聚糖-海藻酸钠肠溶微球的制备和评价

目的:制备阿奇霉素壳聚糖-海藻酸钠肠溶微球,并评价各因素对微球性质的影响.方法:以壳聚糖-海藻酸钠为基质材料,采用复凝聚法制备阿奇霉素壳聚糖-海藻酸钠肠溶微球.通过单因素考察研究对粒径、收率和包封率影响较大的因素,以包封率和释放度为指标进行正交设计优化最佳处方.结果:海藻酸钠浓度为3％、氯化钙浓度为2.5％、壳聚糖浓度为0.25％和投药量为20％为最佳处方.该处方制得的微球形态圆整,粒径分布合理,包封率和收率均较高.体外溶出试验表明,该条件制得的微球在酸中的释放量小于10％,可减少阿奇霉素的胃肠道不良反应;在pH6.8的缓冲液中快速释放,能迅速达到最小抑菌浓度(MIC).结论:阿奇霉素壳聚糖-海藻酸钠肠溶微球能有效避免药物在酸性环境中释放.     

阿司匹林壳聚糖-海藻酸钠微囊处方优化与释药机制研究

目的:制备阿司匹林壳聚糖-海藻酸钠微囊(ACSPM),并研究其处方优化与释药机制。方法:设计正交试验,以包封率为指标优化ACSPM处方并制备微囊,测定其释放度并通过释放动力学模型方程拟合探讨其释药机制。结果:所得微囊大小及含量均匀,最优处方中海藻酸钠浓度、壳聚糖浓度、海藻酸钠与阿司匹林比例分别为3.0%、1.0%、1∶4,体外释放符合Higuchi方程和Peppas方程。结论:该微囊制备工艺方法简单,释药机制以药物扩散为主兼有骨架溶蚀的non-Fickian过程。     

烟酸凝胶骨架缓释片的处方工艺研究

目的:优化烟酸凝胶骨架缓释片处方工艺。方法:采用亲水凝胶骨架材料羟丙基甲基纤维素(HPMC)的2种型号K15M、E15-LV及辅料磷酸氢钙的处方用量为因素设计正交试验,以体外释放度为考察指标,优化烟酸凝胶骨架缓释片的处方,并进行批内和批间体外释放度验证试验。结果:优化处方为HPMC(K15M、E15-LV)分别为4%、40%,磷酸氢钙为25%。所制烟酸凝胶骨架缓释片可持续释药12h,批内释放均一性及批间重现性均良好。结论:所选烟酸凝胶骨架缓释片处方合理,工艺简单。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果EEM的最优处方为:海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

星点设计-效应面法优化尼可地尔胃漂浮缓释片制剂处方

目的:应用星点设计-效应面法对尼可地尔胃漂浮缓释片进行处方优化。方法:采用粉末直接压片法,以制剂辅料中HPMC、十八醇和碳酸氢钠的用量为考察因素,以1,4,8 h的累积释放度和漂浮性能为评价指标,应用星点设计-效应面法优化制剂处方,并对胃漂浮缓释片释药机理做初步研究。结果:最佳制剂处方为:HPMC 60 mg、十八醇40 mg、碳酸氢钠30 mg;经处方验证,体外累积释放度的预测值与实测值偏差<5%,起漂时间<5 min,续漂时间>8 h;经Ritger-Peppas方程拟合,n=0.5357,提示该缓释片体外释放为非Fick扩散,具扩散与骨架溶蚀的双重机制。结论:应用星点设计-效应面法优选出了最佳制剂处方,按最佳制剂处方制备的尼可地尔胃漂浮缓释片具有良好的漂浮性能和缓释特性,制备方法简便。     

中心复合设计法优化盐酸左氧氟沙星缓释片处方

目的:采用中心复合设计法预测盐酸左氧氟沙星缓释片的最优处方。方法:选用羟丙基甲基纤维素和乙基纤维素为骨架材料制备盐酸左氧氟沙星缓释片。采用中心复合设计法,选择体外累积释放百分率为考察指标,对羟丙基甲基纤维素和乙基纤维素用量2个考察因素自变量进行多元线性回归和二项式拟合,对缓释片的最优处方进行预测,并分析缓释片的释药机制。结果:经预测分析,获得最优处方。通过相似因子法比较显示,由此优化处方所制缓释片释放度实测值与预测值基本相符。缓释片体外释药符合一级动力学特征,释药机制为非Fick-ian扩散。结论:中心复合设计法预测性良好,可用于优化处方。     

球面对称设计筛选罗沙替丁缓释片的处方及其释放度考察

目的研究球面对称设计法在缓释片处方优化中的应用并考察其释放度。方法采用球面对称设计法,以海藻酸钠、羟丙基甲基纤维素、十八醇用量3因素为考察对象,对罗沙替丁缓释片的处方进行优化并制备缓释片;另测定释放度,并对数据进行评分及统计学分析。结果采用球面对称设计法,可得到影响因素的二项式方程和优化处方,且试验值与预测值非常接近。结论采用球面对称设计法对罗沙替丁缓释片的处方进行优化和预测可行。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的 对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法 以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果 EEM的最优处方为：海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论 EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

Formulation and In vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures

In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f₂ metric values and found to be similar to the commercial product Bricanyl^®. Reproducible data were obtained when scale-up of the formulation was performed.     

pH-independent sustained release matrix tablet containing doxazosin mesylate: Effect of citric acid

The aim of this study was to develop a pH-independent sustained release matrix tablets of doxazosin mesylate. The matrix tablets were prepared by direct compression technique using polyethylene oxide, sodium alginate and citric acid as a pH modifier. Formulations were evaluated for an in vitro drug release study, erosion study, and the microenvironmental pH was studied using the pH indicator methyl red. For formulations without citric acid, the extent and rate of drug release in simulated gastric fluid were much higher than those in simulated intestinal fluid. By adding the citric acid, the drug release rate in simulated intestinal fluid was increased, and microenvironmental pH values within the tablets were maintained at low pH during drug release. Furthermore, drug release from the matrix tablet containing 20% w/w citric acid was comparable to that from a commercial product, Cardura® XL, and a pHindependent release could be achieved. Therefore, the incorporation of citric acid as a pH modifier to Polyethylen oxide-sodium alginate matrix tablets effectively produced pHindependent doxazocin mesylate release profiles.     

Hybrid drug delivery system for oropharyngeal,cervical and colorectal cancer – in vitro and in vivo evaluation

The present investigation was designed with the intention to formulate a versatile 5-fluorouracil(5-FU) matrix tablet surpassing issues associated with current conventional chemotherapeutic drug delivery systems. The novel 5-FU matrix tablet fulfills therapeutic needs by engineering matrix tablets utilizing chitosan–sodium alginate interpolyelectrolyte complex (IPEC). IPEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The matrix tablets were formulated utilizing IPEC alone and in combination with chitosan, sodium alginate and sodium deoxycholate as permeation enhancer. Pharmaceutical properties, swelling studies, in vitro dissolution and diffusion studies, mucoadhesive studies and in vivo studies were performed for formulated 5-FU. The selected chitosan–sodium alginate IPEC offers pH independent 5-FU release in comparison to alone or physical mixture of chitosan and sodium alginate. Furthermore, novel matrix tablets demonstrated significantly higher bioadhesive properties with controlled 5-FU release without the initial burst effect and also demonstrated a higher permeation of 5-FU. To conclude, the developed novel 5-FU matrix tablets pave way as an excellent alternative for cancer treatment which could potentially minimize the dose dependent side effects and provide better patient compliance.     

In vitro characterization and release study of Ambroxol hydrochloride matrix tablets prepared by direct compression

A series of either hydrophilic or hydrophobic polymers were used to prepare controlled release Ambroxol hydrochloride (AMX) matrix tablets by direct compression. Both the compatibility and flow properties of AMX/polymer mixtures were investigated. The effect of the amount and type of polymer on the physical properties and in vitro drug release was studied and compared to commercially available Ambroxol^® SR capsules. A kinetic study of the release profile of AMX from the prepared matrix tablets was performed. All excipients used in the study were compatible with the model drug. AMX/drug mixtures containing sodium alginate (NA) and hydroxypropylmethyl cellulose (HPMC) showed better flow properties than other polymers used in the study. The in vitro drug release studies showed that matrix tablets formulae containing 10% HPMC (S7) or a combination of 30% NA and 5% HPMC (Ah) exhibited a higher ability to control the release of AMX. The kinetic study revealed that a diffusion controlled mechanism prevailed except when carbopol was used. Formula Ah followed a non-fickian diffusion mechanism similar to Ambroxol^® SR capsules. Both formulae S7 and Ah could be considered as potential candidates for formulation of AMX controlled release matrix tablets.     

鱼腥草素钠缓释片的制备及体外释放特性研究

目的制备鱼腥草素钠缓释片,并考察其体外释放特性。方法分别采用羟丙基甲基纤维素（HPMC）、联合应用HPMC与乙基纤维素（EC）作为骨架材料制备鱼腥草素钠缓释片,以累积释放度为指标,评价其体外释放特性。结果HPMC黏度及用量、EC用量对药物的释放有较大影响,填充剂对药物的释放几乎无影响。缓释片释药结果符合Higuchi方程。结论所制备的鱼腥草素钠缓释片缓释性能良好,其释放机制为非Fick’s扩散。     

响应面法优化肉苁蓉松果菊苷肠溶微球的制备

目的 制备肉苁蓉松果菊苷肠溶微球,筛选最佳制备工艺,并考察其体外释放特性。方法 用离子凝胶-干燥法制备肉苁蓉松果菊苷肠溶微球,以包封率为考察指标,用响应面法优化其制备工艺。结果 制备肉苁蓉松果菊苷肠溶微球最佳工艺参数：海藻酸钠浓度36.33 mg/ml、氯化钙浓度10.82 mg/ml、壳聚糖浓度10.93 mg/ml。结论 优选的工艺稳定、可行,制备的微球包封率高、缓释效果较好。     

葛根素缓释复合骨架片理化性质的研究

目的利用甲壳胺 海藻酸钠的聚合物作为新型缓控释制剂的复合骨架材料 ,并对其性质及影响因素进行研究。方法利用天然高分子材料甲壳胺 (CS) (阳离子型 )与海藻酸钠 (AL) (阴离子型 )模拟在体内条件下形成聚电解质复合物。通过DTA及IR图谱的峰值变化证明这种复合物确实存在 ,形成的关键是控制好两种电解质的比例。结果当WCS∶WAL=2∶3时 ,反应最完全。利用制成的聚电解质复合物 ,制备葛根素缓释复合骨架片 ,缓释效果符合中国药典规定。结论甲壳胺 海藻酸钠形成的复合物可以做缓、控释制剂的骨架材料。     

In vitro evaluation of chitosan coated- and uncoated-calcium alginate beads containing methyl salicylate-lactose physical mixture

Context: Methyl salicylate–lactose physical mixture (1:1 and 1:1.5 ratios) was incorporated into calcium alginate beads by a coacervation method involving an ionotropic gelation/polyelectrolyte complexation approach.

Objectives: This study aims to determine the influence of chitosan coating over the beads on drug entrapment efficiency (DEE) and release characteristics in artificial saliva compared to that of the uncoated beads.

Results and discussion: Changes in formulation parameters (gelation time, concentrations of Ca²⁺ and alginate) resulted in decrease in DEE of chitosan-uncoated beads (p?<?0.05). This is due to the combined effects of drug leach-out from the physical mixture by Ca²⁺ ions, alginate gel matrix cross-linking and free drug diffusion from chitosan-uncoated beads. However, an increment in the DEE was seen for chitosan-coated beads. A rapid drug release profile was noted for uncoated beads, but for chitosan-coated beads a sustained release profile was depicted depending upon the coating conditions. Chitosan-coated beads had reduced swelling and erosion properties and thus behaved as a physical barrier to drug release. Shifting from anomalous transport type to Fickian transport confirmed the formation of physical barrier onto chitosan-coated beads.

Conclusion: Calcium alginate beads could be used as a controlled-release system for methyl salicylate–lactose physical mixture.     

Release behaviour of diclofenac sodium dispersed in Gelucire® and encapsulated with alginate beads

Sustained release polymeric particles containing diclofenac sodium dispersed in Gelucire® matrix and encapsulated in calcium alginate shell were prepared with different drug-to-polymer ratios and also with different concentrations of sodium alginate for a fixed drug-to-polymer ratio in an aqueous environment. Spherical particles were formed by dropping an emulsion of diclofenac sodium in Gelucire® matrix, emulsified with sodium alginate, into calcium chloride solution. The gelled beads formed by ionotropic gelation of alginate with calcium ions showed sustained release of the water soluble drug in in-vitro release study. Drug release was a function of square-root of time, suggesting a matrix diffusion release pattern. The rate of release was significantly suppressed with increasing proportions of Gelucire® in the mixture. Sustained and complete release was achieved with Gelucire® of low melting point and low HLB value. No significant drug release occurred in a dissolution medium of pH 1.5, whereas complete release was observed at pH 6.8, consistent with considerable swelling of the alginate gel at this pH.     

Design,Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3² full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D_{1 h,}D_{6 h}) and time required to 90% drug release (t_90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.