异噻唑啉酮微胶囊的制备表征及释放行为

以二异氰酸酯(TDI)、聚乙二醇4000(PEG)、二羟甲基丙酸(DMPA)和三乙胺(TEA)为原料,制备可水乳化的聚氨酯(WPU).以合成的WPU为囊壁、以异噻唑啉酮衍生物(Sea-nine 211)为囊芯,通过乳化自组装得到防污剂Sea-nine 211微胶囊,用红外光谱、粒径分布和扫描电镜对胶囊进行表征,并采用分...     

Development of Novel Sustained Release Bioadhesive Vaginal Tablets of Povidone Iodine

Iodine has long been used as an antiseptic for the prevention and treatment of vaginal infections. The present study was aimed at the development of rapidly disintegrating, bioadhesive and sustained release vaginal tablets of an iodophore, polyvinylpyrrolidone (povidone iodine), their evaluation and comparison with the marketed formulations. The formulation development included drug-excipient compatibility studies, optimization of performance parameters like disintegration time, bioadhesion and drug release profile and comparison of physical properties and performance parameters with the marketed formulation. The developed formulation provided a sustained release of polymer complexed iodine (up to 8 hrs), rapid disintegration (< 1 min.), desired bioadhesive properties and retention for a prolonged time.     

预交联法制备海藻酸钠复合微球及其缓释性能

采用预交联法制备海藻酸钠(SA)/凹土(ATP)复合微球(PCM)以克服常规制备方法导致微球交联不均匀的缺陷,从而改善微球的缓释性能。将ATP先与Ca~(2+)进行部分离子交换制备Ca~(2+)-ATP,然后在与SA复合过程中同时进行预交联形成交联密度有所提高的微球内核,再采用滴注法制备该复合微球。利用红外光谱、扫描电镜和电子照片对微球结构和形貌进行表征,考察了Ca~(2+)浓度对PCM力学强度、溶胀率、载药和缓释性能的影响。结果表明,PCM在1h的累计释放率由预交联前的68%降为50%,显著改善了微球的"突释"。释放动力学研究表明,微球的释药可用Ritger-Peppas方程很好地拟合,释药速率受骨架溶蚀和药物扩散双重控制。     

壳聚糖/PHB复合缓释微包囊的制备与体外释药评价

用疏水性聚酯PHB外包覆壳聚糖-三聚磷酸钠-阿斯匹林药物缓释体(CPA)制备了壳聚糖/PHB复合缓释微包囊(CPAB),以克服CPA遇酸不稳定的释药特点.用傅立叶红外分光光度计、激光粒度仪、扫描电镜表征了CPAB的组成、粒径及表面形貌.结果显示,CPAB粒径在50～100nm和载药率18.5%时,表面有不均匀的空隙.体外释药评价证实CPAB能有效解决CPA在酸性下的不稳定性,具有长效缓释作用.     

Surelease as granulating liquid in preparation of sustained release matrices of ethylcellulose and theophylline

Objectives: Use of Surelease as a granulation liquid in preparation of granules and matrices of theophylline and ethylcellulose was evaluated.

Materials and methods: Physical mixtures (at 1:1 or 1:1.5 drug:polymer) were granulated using water, Surelease or diluted Surelease as granulating liquid. The granule characteristics (shape, size, flow rate, mechanical properties, friability and release profile) were studied. Afterwards, matrices were manufactured and their crushing strengths, friability and release profiles were determined.

Results: Granulation produced agglomerated particles with better flowability than physical mixtures. Change of granulation liquid from water to Surelease or diluted Surelease led to the marginal increase in size of granules at 1:1 drug:polymer, however, the flow rate and Carr’s index were considerably improved. The hardness, elastic modulus, friability and rate of drug release were not affected by granulation liquid. Increase in polymer content resulted in reduction in size of granules, flow rate, elastic modulus and rate of drug release. However hardness of the granules was unaffected. Granulation process and granulation liquid did not affect the hardness, and dissolution rate of matrices at 1:1 drug:polymer, while the use of Surelease or diluted Surelease as a granulating liquid, increased the hardness and decreased drug release rate at 1:1.5 drug:polymer. Matrices prepared from Surelease or diluted Surelease showed similar characteristics.

Conclusions: Surelease is a suitable granulating liquid for preparation of ethylcellulose matrices especially when high amount of polymer is used and could not only improve the flow and compatibility of the granules, but also help in reducing the rate of drug release.     

Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as Immediate Release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the . The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.     

阿司匹林表面印迹微球的制备与药物缓释性能评价

采用表面印迹技术,选取γ-氨丙基三甲氧基硅烷(APTS)和甲基丙烯酰氯修饰的硅胶为载体,以阿司匹林(Asp)为模板分子,丙烯酰胺(AM)为功能单体,乙二醇二甲基丙烯酸酯(EDGMA)为交联剂,在乙腈溶液中合成了阿司匹林表面分子印迹聚合物微球(MIPs)和非印迹聚合物微球(NIPs)。通过紫外、红外光谱、扫描电镜、透射电镜、热重分析以及吸附实验进行了表征并进行了药物扩散实验。结果表明,MIPs平衡吸附量可达164.40μmol/g,对苯甲酸(BA)和水杨酸(SA)的分离因子达到3.15和3.32,有很好的热稳定性和选择性吸附能力;MIPs持续释药时间是NIPs的2.6倍,有很好的缓释效果和应用价值。     

Evaluation of Mucilage of Hibiscus rosasinensis Linn as Rate Controlling Matrix for Sustained Release of Diclofenac

This article reports the exploitation of novel hydrophilic excipient, that is, mucilage from Hibiscus rosasinensis Linn, for the development of sustained release tablet. Swelling ratio and flow properties analyses of dried mucilage powder were carried out. A 3² full factorial design was used. In factorial design, amounts of dried mucilage and dibasic calcium phosphate (DCP) were taken as independent factors and percentage drug release in 60 and 300 min and time for 80% drug release as dependent variables. Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. DS tablets were evaluated for hardness, friability, weight variation, in vitro drug release and water uptake, and mass loss study. The dried mucilage powder shows superior swelling capacity and excellent flow properties. Prepared tablets have acceptable hardness, friability, and uniformity in weight. It was found that batch HD8 fulfills all selected criteria. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Water uptake was independent whereas mass loss was dependent on agitation speed. The concept of similarity factor (f₂) was used to prove similarity of dissolution profile in distilled water and phosphate buffer and was found to be 90.68. It was concluded that mucilage can be used as release-retarding agent for 12 h when the drug–mucilage ratio was 1:1.5. So, matrix tablet containing dried mucilage is most suitable for sustained release of DS.     

Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.     

内盐凝胶的制备及对烟酰胺的控释

以甲基丙烯酸二甲基氨基乙酯（DMAE-MA）、衣康酸（IA）、亚甲基双丙基酰胺（BIS）和过硫酸钾（KPS）为原料在室温下制备内盐凝胶。研究了原料配方对凝胶形成的影响、内盐凝胶的吸水动力学及溶胀机制、凝胶的pH值敏感性以及对烟酰胺的负载与负载凝胶在不同pH值介质中的释放行为,并用红外光谱对凝胶结构进行了表征。结果表明,n（IA）/n（DMAEMA）〉1后将降低单体的转化率,不利于凝胶的形成;内盐凝胶不具有高吸水性,其吸水溶胀机制符合Fickian扩散;在pH值为12的缓冲溶液中溶胀率比在pH值为3的缓冲溶液中高;凝胶对烟酰胺的负载率可以超过200%。在25℃下,烟酰胺在pH值为3的介质中释放比在pH值为12的介质中释放快。     

聚乙二醇共价交联海藻酸钠凝胶制备及其药物缓释性能

为了增强海藻酸钠凝胶的稳定性以及对药物的缓释效果,将海藻酸钠用聚乙二醇(PEG200)交联,在水溶液中用对甲苯磺酸催化、经过酯化反应合成了共价交联的海藻酸钠凝胶;通过红外光谱、热重分析和X-射线分析对产物进行了表征。与钙离子交联的海藻酸钠凝胶相比,共价交联海藻酸凝胶在仿生体液中结构稳定,在模拟体液中完全降解时间持续到60天。凝胶对牛血清白蛋白的载药率达到11.5%,显示出明显的缓释效应和pH响应性能,具有作为pH控释和缓释药物载体的应用前景。     

Chitosan-Based Thermosensitive Hydrogel Containing Liposomes for Sustained Delivery of Cytarabine

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2?±?2.58%) with the mean diameter of 220?±?6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t_1/2 (28.86 h) and AUC 2526.88 μg/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.     

Evaluation and Floating Enhancement of Levodopa Sustained Release Floating Minitablets Coated with Insoluble Acrylic Polymer

This article describes the in vitro evaluation and the enhancement of the floating properties of coated sustained release (SR) minitablets (MTs). The evaluated system consisted of a 3-mm drug-containing gas-generating core prepared by melt granulation and subsequent compression, which was then coated with a flexible polymeric membrane. Eudragit® RL30D and acetyl triethylcitrate were used as a film former and a plasticizer, respectively. The coating level was fixed at 20% (wt/wt). The optimally coated floating MTs floated within 10 min and remained buoyant for more than 13 h, regardless of the pH of the test medium. By evaluating the dissolution profiles of levodopa at different pH, it was found that the release of levodopa was sustained for more than 12 h regardless of the pH, even if the coating did not cancel the effect of the pH-dependent solubility of the active drug. Finally, the robustness of the coated floating MTs was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.     

Directly Compressed Mini Matrix Tablets Containing Ibuprofen: Preparation and Evaluation of Sustained Release

ABSTRACT

Directly compressed mini tablets were produced containing either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling agent. The dynamics of water uptake and erosion degree of polymer were investigated. By changing the polymer concentration, the ibuprofen release was modified. In identical quantities, EC produced a greater sustaining release effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen release. For EC formulations, the contribution of diffusion was predominant in the ibuprofen release process. For HPMC preparations, the drug release approached zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm diameter were produced.     

形状记忆型水凝胶的制备及其在药物控制释放中的应用

以戊二醛为交联剂,制备了pH敏感性明胶-果胶水凝胶(GT-PT)和明胶-辛基果胶水凝胶(GT-OPT),研究了交联剂用量、温度、pH值对凝胶溶胀性能的影响及溶胀-消溶胀性能.结果表明,当温度在30～60℃时,凝胶的溶胀率随温度的升高而增大;且具有明显的pH敏感性,碱性条件下的溶胀率大于酸性条件下的溶胀率;不同pH值条件下,明胶-果胶水凝胶具有“形状记忆”功能.包埋在水凝胶中的牛血清蛋白在pH=1.0时的释药率大于pH=7.8和pH=9.18时的释药率.此类水凝胶有望用于蛋白质的pH值及温度控制释放.     

负载对苯二酚的聚苯乙烯-二乙烯苯交联微球的制备及缓释行为(英文)

采用超声波改进的二步种子溶胀法制备粒径2.4～9μm的多孔聚苯乙烯-二乙烯苯微球,单分散的聚苯乙烯微球由分散聚合制备并以其作为种球。论文考察了种球类型、超声分散时间、种球和溶胀剂以及交联单体比率等因素对多孔微球形貌及孔结构的影响,并采用扫描电镜、BET等手段对微球性能进行了表征。研究发现超声辅助分散的引入可使产物的粒径分布更窄并将第一步溶胀时间由传统的24h缩短至10h。实验结果表明:种球的单分散性对最终产物的形貌有决定性影响,它的任何形貌缺陷都将在最终产物中被扩大;随着溶胀剂/种球比率和交联单体/种球比率的增加,最终产物的粒径和比表面积增大,孔径减小。以对苯二酚为模型组分,考察其在制得的多孔微球上的缓释行为,发现制得的多孔聚合物微球在用作化妆品活性组分载体时,表现出良好的缓释性能。     

Novel Polylactide‐Based Release Systems for Local Antibiotic Therapies

Antibiotic delivery systems based on biodegradable polymers have found considerable interest for the local therapy of bone infections. In this study polylactide based polymer and composite delivery systems for the release of gentamicin have been fabricated from poly‐L‐lactides and a poly(L‐lactide‐co‐D,L‐lactide) as well as biodegradable inorganic fillers (calcium hydrogen phosphate, calcium sulfate dihydrate). The in vitro release profiles of the polymer delivery systems were characterized by an initial burst release followed by a sustained release of small gentamicin amounts up to 3 weeks. In the composite delivery systems a loss of retardation was observed with an increasing content of inorganic filler material. It was found that the in situ complex formation of gentamicin by adding defined amounts of sodium dodecyl sulfate represents a valuable tool to overcome this problem and to modulate the release profile of the delivery systems in a wide range. Under in vitro conditions, calcium sulfate dihydrate containing delivery systems are rapidly degraded in aqueous medium within several months. Based on these results, the developed composite delivery systems are promising candidates for the efficient treatment of bone infections.     

Preparation and In Vitro/In Vivo Evaluation of Gliclazide Loaded Eudragit Nanoparticles as a Sustained Release Carriers

ABSTRACT

The aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased t_min (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.     

Sustained Release of Diclofenac from Polymer-Containing Suppository and the Mechanism Involved

Sustained release of diclofenac sodium (DcNa) from suppositories composed of triglycerides and polymer was investigated by dissolution testing through an artificial membrane. DcNa was slowly released from a suppository containing carboxyvinyl polymer (CVP), and the extent of the release decreased with the amount of CVP added. Little effect was noted with the addition of other water-soluble polymers, such as hydroxyethylcellulose (HEC), xanthan gum, and polyvinylalcohol (PVA). When sodium benzoate was used instead of DcNa, a similar result was obtained with the addition of CVP. The result of release rate analysis together with the viscosity and pH in these cases showed that the reduction of solubility and diffusion due to sodium exchange between DcNa and CVP played an important role in the sustained release from the suppository. Also, in comparison with the results when CVP was not used, the plasma concentration profile of diclofenac after the administration of CVP suppository displayed a twofold longer half-life time.