Enhancement of griseofulvin release from liquisolid compacts

The potential of hydrophilic aerogel formulations and liquisolid systems to improve the release of poorly soluble drugs was investigated using griseofulvin as model drug. The in vitro release rates of this drug formulated as directly compressed tablets containing crystalline griseofulvin were compared to aerogel tablets with the drug adsorbed onto hydrophilic silica aerogel and to liquisolid compacts containing the drug dissolved or suspended in PEG 300. Furthermore, the commonly used carrier and coating materials in liquisolid systems Avicel® and Aerosil® were replaced by Neusilin®, an amorphous magnesium aluminometasilicate with an extremely high specific surface area of 339 m²/g to improve the liquisolid approach.Both the liquisolid compacts containing the drug dissolved in PEG 300 and the aerogel tablets showed a considerably faster drug release than the directly compressed tablets. With liquisolid compacts containing the drug suspended in PEG 300, the release rate increased with rising fraction of dissolved drug in the liquid portion. It could be shown that Neusilin® with its sevenfold higher liquid adsorption capacity than the commonly used Avicel® and Aerosil® allows the production of liquisolid formulations with lower tablet weights.     

Self nano-emulsifying simvastatin based tablets: design and in vitro/in vivo evaluation

The aim of this work is to improve the oral bioavailability of poorly water soluble drug, simvastatin (SV) through combining the advantages of self-nanoemulsifying systems (SNEs) and tablets. Ternary phase diagram was constructed using Labrafil, Tween 80 and Transcutol, in order to evaluate self-nanoemulsification domain. The particle size distribution and zeta potential of the prepared systems were evaluated using Malvern Zetasizer. Liquisolid powders were prepared using Aeroperl^® as a coating material and Avicel^® or Starch 1500 as carrier materials, the powder flow properties were then evaluated. Compressed SV SNE based tablets were evaluated regarding their physical characteristics, in-vitro release properties as well as in-vivo pharmacokinetic evaluation in six healthy human volunteers using a validated LC/MS/MS method. The in-vitro release results revealed that the developed SNE based tablets improved the release of SV significantly, compared to commercially available SV tablets (Zocor^®). The optimal SV SNE tablet formulation was S3St10 (10% Labrafil, 60% Tween 80, and 30% Transcutol). The in-vivo evaluation of S3St10 revealed that rapid and enhanced absorption of SV could be obtained from the SNE based tablet, with a 1.5 fold increase in bioavailability than that obtained after administration of Zocor^®. Hence such an approach could be promising in improving the bioavailability of SV.     

Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: Development,optimization and in vitro/in vivo studies

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X1 (PG or PEG), drug concentration, X2 (10% and 20%), type of coat, X3 (Aerosil® and Aeroperl®) and excipients ratio, X4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X1, X2, X3 and X4) were PEG, 10%, Aerosil® and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv® as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.     

Casein-based formulations as promising controlled release drug delivery systems

Casein, the major milk protein, forms an integral part of the daily diet in many parts of the world. Casein possesses a number of interesting properties that make it a good candidate for conventional and novel drug delivery systems. This article reviews approaches aimed to associate bioactive molecules to casein and analyze the evidence of their efficacy in modifying the release and/or improving the bioavailability of the associated molecules. The ability of casein to modify drug dissolution from compacts was reported. The high tensile strength of casein films, favors its use as an acceptable film-coating for tablets. Naturally occurring genipin and a natural tissue enzyme, transglutaminase, were used as crosslinkers to prepare novel casein-based hydrogels for the controlled release of bioactives. Casein floating beads were developed to increase the residence time of drugs in the stomach based on its emulsifying and bubble-forming properties. Casein-based microparticles entrapping bioactive molecules were prepared via emulsification-chemical crosslinking with glutaraldehyde, enzymatic crosslinking by transglutaminase, simple coacervation and electrostatic complexation. Casein nano-formulations were also prepared to deliver nutraceuticals and synthetic drugs via enzymatic crosslinking, graft copolymerization, heat-gelation and polyelectrolyte ionic complexation. It can be concluded that casein-based formulations are promising materials for controlled drug delivery.     

茯苓皮总三萜液固压缩片的处方研究

目的采用星点设计-效应面法优选茯苓皮总三萜液固压缩片处方,以提高其体外溶出度。方法通过预试验和单因素考察初步确定所选辅料及比例,以溶出度为考察指标,采用星点设计-效应面法进一步优化处方,对最优处方的茯苓皮总三萜液固粉末、茯苓皮总三萜原料、液固压缩片辅料混合粉末进行差示扫描量热分析(DSC),考察药物与辅料之间是否存在相互作用以及药物在液固压缩制剂中的存在形式。结果茯苓皮总三萜液固压缩片的最优处方为药液比1∶1.67,载体材料与涂层材料的比值(R值)为18.25,崩解剂加入量为8%,PVP-XL 10与CMS-Na的比值为1.27,压制硬度为40~50 N。DSC分析表明辅料与茯苓皮总三萜不存在相互作用,药物在液固粉末中是以非晶型形式存在的。结论茯苓皮总三萜液固压缩片处方合理,可提高茯苓皮总三萜的体外溶出度,并将药物从结晶状态转化为分子或无定形状态。     

Drug release from liquisolid systems: speed it up,slow it down

Introduction: Today, the properties of many new chemical entities have shifted towards higher molecular weights and this in turn increases the lipophilicity hence decreasing aqueous solubility. The low solubility of drugs usually has in vivo consequences such as low bioavailability, increased chance of food effect and incomplete release from the dosage form.

Areas covered: The present review discusses the advantages of the liquisolid technology in formulation design of poorly water soluble drugs for dissolution enhancement and highly water soluble drugs for slow release pattern.

Expert opinion: With the advent of high throughput screening and combinatorial chemistry, it has been shown that most of the new chemical entities have a high lipophilicity and poor aqueous solubility, hence poor bioavailability. In order to improve the bioavailability, the release rate of these drugs should be enhanced. Although there are multiple technologies to tackle this issue, they are not cost effective due to the involvement of sophisticated machinery, advanced preparation techniques and complicated technology. As the liquisolid technology uses a similar production process as the conventional tablets, this technology to improve the release rate of poorly water soluble drugs will be cost effective. This technology also has the capability to slow down drug release and allows preparing sustained release tablets with zero order drug release pattern. The excipients required for this technology are conventional and commonly available in the market. The technology is in the early stages of its development with extensive research currently focused on. It is envisaged that the liquisolid compacts could play a major role in the next generation of tablets.     

液固压缩技术速释茯苓皮总三萜片中松苓新酸和去氢依布里酸的机制探索

目的:探讨液固压缩技术速释茯苓皮总三萜片中松苓新酸和去氢依布里酸的机制。方法:以松苓新酸和去氢依布里酸为指标成分,比较茯苓皮总三萜液固压缩片与原料药体外溶出度的差异,采用差示扫描量热法(DSC)对茯苓皮总三萜原料药、液固压缩片粉末和液固压缩片辅料混合粉末进行物相表征。结果:液固压缩技术可显著提高松苓新酸和去氢依布里酸的溶出速率。茯苓皮总三萜液固压缩片中松苓新酸和去氢依布里酸在120 min时的总溶出度92%,t50(溶出总浓度50%所需时间)和tD(溶出总浓度63.2%所需时间)分别为11.18,22.71 min;总三萜原料中松苓新酸和去氢依布里酸的总溶出度29%,t50和tD分别为231.06,359.23 min。DSC分析显示辅料对茯苓皮总三萜不存在相互作用,液固压缩片粉末的DSC曲线上,主药吸收峰完全消失,说明药物在液固粉末中是以非晶型形式存在。结论:液固压缩技术可改善茯苓皮总三萜的溶出度,使难溶性药物快速释药。     

Liquisolid Tablets for Dissolution Enhancement of a Hypolipidemic Drug

This investigation was aimed to improve the dissolution rate of the poorly soluble drug lovastatin, by formulating it as a liquisolid compact. Different liquisolid compacts were prepared using mathematical formulae to calculate the required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Avicel PH 200, Cab-O-Sil, sodium starch glycolate and PEG 400 were employed as carrier, coating material, disintegrant and non-volatile liquid vehicle, respectively. The various drug to liquid and carrier to coating ratio were used to prepare liquisolid compacts. The formulated liquisolid tablets were evaluated for weight variation, hardness, drug content, friability and disintegration time. The in vitro release characteristics of the drug from tablets formulated by direct compression and liquisolid technique were compared in two different dissolution media. The tableting properties of the liquisolid compacts were within the acceptable limits and drug release rates were distinctly higher as compared to directly compressed tablets. The FTIR spectra showed no interaction between drug-excipient and disappearance of the characteristic absorption band of lovastatin in liquisolid formulations could be attributed to the formation of hydrogen bonding between the drug and liquid vehicle, which resulted in dissolution enhancement. Thus, the liquisolid technique was found to be a promising approach for improving the dissolution of a poorly soluble drug like lovastatin.     

液固压缩技术速释α-细辛脑的机制探讨

目的:探讨液固压缩技术使α-细辛脑快速溶出的机制.方法:以聚山梨酯-80为液体赋形剂,微晶纤维素PH-101为载体材料,微粉硅胶(R) 200为涂层材料,制备药液比1∶4的α-细辛脑液固压缩片,比较其与市售普通片的溶出度,通过测定X-射线衍射(XRD)和崩解时限,探讨该压缩片的速释机制.结果:液固压缩片中α-细辛脑在5 min时,溶出度＞80％.XRD表明液固压缩片中无α-细辛脑的特征峰.结论:采用液固压缩技术可改善药物润湿性,增加药物溶出时有效表面积,使难溶性药物快速溶出.