Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

曲安奈德益康唑霜在湿疹类皮肤病中的应用

目的：观察曲安奈德益康唑霜治疗湿疹皮肤病的疗效。方法：选择本院116例湿疹皮肤病患者,用曲安奈德益康唑霜涂抹患处,每日2次,3周为1个疗程。结果：痊愈率为26.7%,显效率为62.97%,总有效率为89.7%。结论：曲安奈德益康唑治疗湿疹类皮肤病安全有效。     

反相离子对高效液相色谱梯度洗脱测定复方硝酸益康唑乳膏含量

目的　建立复方硝酸益康唑乳膏含量测定的方法。方法　色谱柱为辛烷基硅烷键合硅胶柱(L i Chrospher C8柱 ,5 μm,4 .6 mm× 2 5 0 mm) ,检测波长 2 2 7nm,采用 A相 (85 %磷酸溶液 1ml,加无水己烷磺酸钠 0 .94 g,溶于 72 0 ml水中 ,加乙腈 14 0 ml,异丙醇 14 0 ml) - B相 (85 %磷酸溶液 1ml,加无水己烷磺酸钠0 .94 g,溶于 10 0 ml水中 ,加甲醇 90 0 ml)为流动相进行线性梯度洗脱 (A相起始比例为 10 0 % ,2 5 min内 B相上升为 10 0 % ,保持该比例至硝酸益康唑完全洗脱 ) ,流速为 1ml/ min,柱温为 4 0℃ ,进样量为 2 0 μl,内标物质为对羟基苯甲酸乙酯。结果　硝酸益康唑在 0 .3～ 0 .8mg/ ml,曲安奈德在 0 .3～ 0 .8mg/ ml,苯甲酸在 0 .0 6～0 .16 mg/ ml范围内 ,浓度与其峰面积均呈良好线性关系 (r=0 .9999,n=6 ) ,平均回收率分别为硝酸益康唑10 1.5 % ,曲安奈德 10 0 .3% ,苯甲酸 98.8%。结论　本法快速、准确 ,可同时测定复方硝酸益康唑乳膏中硝酸益康唑、曲安奈德、苯甲酸的含量。     

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.     

Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique

Abstract

Purpose: Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen’s photoprotection were impaired by the microencapsulation process. Methods: The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. Results: The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53–102.2%), average particle sizes between 28.5 and 60.0?µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. Conclusion: The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.     

瘢痕子宫再次妊娠产妇经阴道分娩的效果分析

目的 探讨瘢痕子宫再次妊娠产妇经阴道分娩的临床效果.方法 100例瘢痕子宫再次妊娠产妇,按分娩方式不同分为阴道分娩组和再次剖宫产组,各50例.比较两组产妇的相关指标(出血量、住院时间及住院费用)、分娩成功情况、并发症发生情况、抗生素应用情况及新生儿Apgar评分、窒息情况.结果 阴道分娩组产妇出血量(135.83±24...     

正交设计法优化硝酸益康唑的合成工艺

目的:优化抗真菌药物硝酸益康唑的合成工艺。方法:采用正交设计法,重点考察反应温度、催化剂、反应时间及溶剂四个因素对收率的影响。结果:溶剂对反应收率的影响最为显著,其次是反应时间和催化剂。结论:新工艺原料价廉易得,反应条件温和,后处理简便,收率高。     

分娩时一对一心理疏导对阴道分娩产妇应激状态影响的临床研究

目的研究分娩时一对一心理疏导对阴道分娩产妇应激状态的影响。方法选择在本院阴道分娩的产妇作为研究对象,随机分为分娩时给予一对一心理疏导的观察组和常规处理的对照组,检测产妇的生理应激血糖水平、血胰岛素水平,观察心理应激指标NRS、HAMA、HAMD评分。结果观察组分娩后NRS、HAMA、HAMD评分及血糖水平均低于对照组,血胰岛素水平高于对照组。结论分娩时一对一心理疏导能够改善阴道分娩产妇的应激状态。     

产程中静脉注射地西泮对阴道分娩产程和新生儿的影响

目的 分析产程中静脉注射地西泮对阴道分娩产程和新生儿的影响.方法 选取2009年1月～2010年3月于本院分娩的初产妇180例,将其随机分为观察组和对照组各90例,观察组在人工破膜基础上,静脉注射地西泮10 mg,对照组采用阴道分娩的常规处理,在分娩过程中不应用地西泮.观察记录两组的产程和新生儿窒息与产后出血的发生情况.结果 观察组产妇的总产程为（9.1±1.5）h,对照组产妇的总产程为（11.9±1.2）h,观察组产妇的总产程时间明显短于对照组,差异有统计学意义（P＜0.05）;观察组和对照组孕妇的新生儿窒息率分别为6.7％和18.9％,差异有统计学意义（P＜0.05）.观察组产后子宫收缩出现乏力,血量增加,平均出血量为310 ml,对照组的平均出血量为150 ml,两组间差异有统计学意义（P＜0.05）.结论 于产程活跃期注射地西泮能够明显缩短孕妇产程,加速宫颈口的扩张,但应积极预防新生儿窒息和产后出血的发生.     

剖宫产与阴道分娩对产妇近期并发症的影响

目的：探讨剖宫产和阴道分娩对产妇近期并发症的影响。方法选取2010年7月~2012年6月在本院分娩的1878例产妇,根据产妇的要求按分娩方式将产妇分成阴道分娩组（782例）和剖宫产组（1096例）,比较两组的并发症发生率。结果两组的子宫破裂发生率差异无统计学意义（P>0.05）,阴道分娩组的产褥感染、产后出血、产后尿潴留发生率明显低于剖宫产组（P<0.05）。结论剖宫产方式会明显增高产后并发症发生率,阴道分娩的产后并发症发生率则明显较低,应提倡阴道分娩。     

瘢痕子宫再次妊娠分娩方式的选择及经阴道分娩安全性的临床分析

目的：观察瘢痕子宫再次妊娠选择不同分娩方式的临床情况并分析经阴道分娩的安全性。方法选取2011年7月~2014年12月本院收治的瘢痕子宫再次妊娠产妇225例,其中选择阴道试产分娩产妇107例作为研究组,选择再次剖宫产分娩产妇118例作为对照A组,另选取同期首次妊娠阴道分娩产妇90例作为对照B组,比较3组的临床情况。结果225例再次妊娠产妇中,107例(47.56%)自愿选择且适宜阴道分娩,试产成功71例(66.36%)(观察组),118例(52.44%)自愿要求或具有剖宫产指征;观察组产妇的的产时、产后出血量明显少于对照A组(剖宫产分娩),住院时间明显短于对照A组,术后并发症发生率明显低于对照A组(P<0.05);观察组产妇的产后出血量、产程时间、住院时间、试产成功率及新生儿评分与对照B组差异无统计学意义(P>0.05)。结论瘢痕子宫再次妊娠产妇选择实施阴道分娩,相比实施剖宫产仍然具有较明显的优势,亦有一定的风险,但实施严格控制阴道试产适应证与禁忌证、加强产时监护等措施能有效提高其安全性与可行性,从而促进临床自然分娩。     

HPLC法测定硝酸布康唑阴道乳膏中硝酸布康唑的含量

目的建立测定硝酸布康唑阴道乳膏中硝酸布康唑含量的HPLC法。方法色谱柱为Luna SEX(250 mm×4.6 mm,5μm)阳离子交换柱,流动相为0.016 6 mol·L~(-1)醋酸钾溶液(用冰醋酸调pH值至4.3)-甲醇(27:73,V/V),检测波长225 nm,流速1.1 mL·min~(-1)。结果硝酸布康唑为5.164～41.312 mg·L~(-1)时线性关系良好(r=0.999 8,n=5),平均回收率为99.71% (RSD=0.6%)。结论本法操作简便、灵敏度高、重现性好。     

Development,optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery

Abstract

The present research work was aimed at development and optimization of alginate mucoadhesive microspheres of carvedilol for nasal delivery to avoid first pass metabolism and to improve the therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared by a water-in-oil (w/o) emulsification technique. A 2³ factorial design was employed with drug : polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size of the microspheres and in vitro mucoadhesion were the dependent variables. Regression analysis was performed to identify the best formulation conditions. Particle size was analysed by dynamic laser light diffraction technique and found to be in the range of 26.36–54.32 µm, which is favourable for intranasal absorption. The shape and surface characteristics were determined by scanning electron microscopy (SEM) which depicted the spherical nature and nearly smooth surfaces of the microspheres. The percentage encapsulation efficiency was found to be in the range between 36.62–56.18. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 69.25–85.28. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of carvedilol in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated non-Fickian or anomalous type of transport for the release of carvedilol from the microspheres.     

Pectin‐based microspheres for colon‐specific delivery of vancomycin

Objectives The aim of this study was to describe a colon‐specific delivery system based on pectin hydrogels formed by complexation with chitosan. Methods Hydrogels were prepared at different weight ratios (4: 1, 7: 1, 10: 1; pectin/chitosan), loaded with vancomycin hydrochloride (2: 1, 4: 1; polymer/drug weight ratio) and collected by spray‐drying. The microspheres obtained were characterized in terms of morphology, swelling behaviour, mucoadhesive properties and drug loading efficiency. The influence of different pectin/chitosan hydrogels on the release behaviour of microspheres at pH 2.0, 5.5 and 7.4 were evaluated in vitro with and without pectinolytic enzyme. Key findings The results showed that water uptake was increased by raising the environmental pH (from 2.0 to 7.4) and the pectin/chitosan weight ratio, while drug availability was increased by raising the environmental pH (from 2.0 to 7.4) and decreased by raising the pectin/chitosan weight ratio. In the presence of pectinase, the glycoside bonds of pectin were degraded and a considerable amount of drug was released in a short time. Conclusions This study suggested that pectin/chitosan microspheres were able to limit the release of vancomycin under acidic conditions and release it under simulated colonic conditions, confirming their potential for a colon‐specific drug delivery system.     

Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery

This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15?min and rest of the drug was released within 60?min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with ^99mTc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug.     

瘢痕子宫再次妊娠的高龄产妇经阴道分娩的安全性和可行性分析

目的 探讨瘢痕子宫再次妊娠的高龄产妇经阴道分娩的安全性和可行性。 方法 回顾性分析2016年2月1日至2017年8月1日在安徽医科大学附属宿州医院住院的瘢痕子宫再次妊娠的100例高龄产妇临床资料,分为3组,剖宫产组(ERCD) 50 例、阴道分娩组(VBAC)32例、阴道试产失败组(TOLAC) 18例,同期选取无瘢痕子宫经阴道分娩产妇40例作为对照组,比较各组分娩结局。 结果 各组年龄、孕周、新生儿出生体质量、新生儿评分等比较差异无统计学意义(P＞0.05);ERCD组、TOLAC组的住院时间、住院费用及产后出血量均高于VBAC组和对照组(P＜0.05)。 结论 在充分尊重产妇意见的前提下,瘢痕子宫再次妊娠的高龄产妇当身体条件和各项指标满足阴道分娩要求时可采取阴道试产,临床工作者在试产过程中严密监测产程进展及胎儿状况,及时妥善处理好各种突发异常情况,瘢痕子宫再次妊娠的高龄产妇选择阴道分娩具有一定的安全性和可行性。     

Wheat germ agglutinin-conjugated chitosan–Ca–alginate microparticles for local colon delivery of 5-FU: Development and in vitro characterization

The aim of this work was to prepare lectin-conjugated chitosan–Ca–alginate microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU) for efficient local treatment of colon cancer. MPs were prepared by a novel one-step spray-drying technique and after wheat germ agglutinin (WGA) conjugation, they were characterized for size, swelling behavior, surface charge, entrapment efficiency and in vitro drug release. Prepared particles were spherical, with 6.73 μg/mg of WGA conjugated onto their surface. The size and zeta potential increased after conjugation, from 6.6 to 14.7 μm and from 9.6 to 15.3 mV, while drug encapsulation was 75.6 and 72.8%, respectively after conjugation. The swelling behavior of beads was mainly determined by properties of the cross-linked chitosan–alginate network. In vitro drug release studies carried out in simulated in vivo conditions with respect to pH, confirmed the potential of the particles to release the drug in a controlled manner. Also, the drug release was not significantly affected by WGA conjugation. The retention of biorecognitive activity of WGA after covalent coupling to MPs was confirmed by haemagglutination test. Functionalized MPs showed excessive mucoadhesiveness in vitro, due to the positive surface charge, pH-dependent swelling of the matrix and lectin–sugar recognition.     

Development of a mucoadhesive delivery system for control release of doxepin with application in vaginal pain relief associated with gynecological surgery

The main purpose of this study was to develop a semisolid mucoadhesive formulation for the non-invasive vaginal administration of doxepin (DOX) for relief of pain derived from the scarring process after surgery. An orafix^® platform loading DOX was tested for adequate stability, rheology and vaginal mucoadhesion capacity. The formulation exhibited appropriate pH and was microbiologically stable. The rheological studies confirmed its pseudoplastic and thixotropic nature with prevalence of the elastic behavior component over the viscous one. Appropriate syringeability and spreadability results were also confirmed. Different experiments showed adequate mucoadhesion capacity even in the presence of simulated vaginal fluid. Finally, DOX release, permeation and retention in vaginal mucosa studies were also accomplished with promising results. DOX release kinetics followed the modified Higuchi model and the permeation studies did not render such high values as to suggest potential systemic absorption which could lead to undesirable systemic side effects. Therefore, we can hypostatize that the proposed formulation may assist to fill in the therapeutic gap regarding pure pain relief at local level in vagina.     

The relationship between mucoadhesive polymers and surface coating in tablets for the controlled colonic delivery of a poorly water-soluble drug

BackgroundThe mucoadhesive polymers play an important role in targeted and controlled drug delivery.ObjectivesThis study aimed to investigate the drug release behaviour and interpret the role of mucoadhesive polymers involved in the coating layer of mucoadhesive tablets for the sustained release of a poorly water-soluble drug.MethodsA solid dispersion of prednisolone and zein was used in the core tablets created with two mucoadhesive polymers, which included Carbopol 940 and hydroxypropyl methylcellulose K4M. In addition, the properties of a single-layer coating, created from the combination of zein and Kollicoat MAE 100P to delay release through the upper parts of the gastrointestinal tract, were investigated in the presence of the above mucoadhesive polymers; these properties included drug dissolution, mucoadhesion, surface morphology, swelling and erosion.ResultsThe mucoadhesive polymer concentrations and types were integrated not only into the core tablets through a swelling/erosion mechanism but also into the surface polymer coatings for controlled drug release. HPMC was preferred in the formulations due to the ability to form pores on the surface coating, allowing water uptake so that the coating could control drug release for a later stage via a swelling/erosion mechanism.ConclusionThe proposed mechanism determined in this project could be beneficial in the selection of polymers for applications targeting the colon with coated mucoadhesive tablets. Open in a separate windowGraphical abstract