基于液固压缩技术葛根总黄酮片速释机理探究

目的:探讨液固压缩技术提高葛根总黄酮溶出度的机制。方法:采用液固压缩技术制备葛根总黄酮速释片,比较液固压缩片与原料药、市售片的溶出度,通过差示扫描量热法(DSC)、粉末接触角测定仪等探讨液固压缩技术的增溶机制。结果:葛根总黄酮液固压缩片较市售片、原料药的溶出有大幅度提高。DSC表明葛根素的特征峰消失,随着添加剂PVPK30占药物溶液比例的增加,液固压缩粉末的接触角逐渐减小。结论:液固压缩技术可提高葛根总黄酮溶出时的有效表面积,改善药物润湿性,使难溶性药物快速释放。     

基于液固压缩技术黄芩苷固体自微乳化释药系统的制备研究

目的:基于液固压缩技术制备黄芩苷固体自微乳化释药系统。方法:运用液固压缩技术,通过载体材料的筛选,体外溶出度的测定,筛选黄芩苷固体自微乳化释药系统的最佳处方。结果:以微晶纤维素为载体材料,溶出50%,仅需要6.4min,明显优于原料药和市售片。结论:运用液固压缩技术制备黄芩苷固体自乳化释药系统,方法简单,且可很好改善黄芩苷的溶出。     

液固压缩技术在水飞蓟素制剂方面的应用

目的探讨制备水飞蓟素液固压缩片的处方,研究水飞蓟素液固压缩片的优势。方法通过不同处方,探讨水飞蓟素液固压缩片的制备;并与水飞蓟素原料药溶出度的比较。结果液固压缩片较原料药的溶出度大幅度提高,在15 min时,溶出至少达到80%。片剂质量合格,在崩解时限上具有明显优势,可在100 s内完全崩解。结论液固压缩技术可应用于难溶性药物水飞蓟素的制剂,并且具有一定的优势。     

黄豆苷元半固体骨架型胶囊处方的初步研究

目的:采用半固体骨架技术提高黄豆苷元的体外溶出度。方法:采用熔融法制备黄豆苷元半固体骨架胶囊,比较不同载体材料聚氧乙烯(40)硬脂酸酯(S-40)、泊洛沙姆、聚乙二醇(PEG)4000,不同含药量(2%、4%、6%),表面活性剂吐温-80不同用量(15%、20%、25%、30%)对其体外溶出度的影响并与市售胶囊进行比较。结果:上述3种影响因素中溶出度较优的选择为采用S-40为载体,含药量为2%,吐温-80用量20%。所制胶囊体外溶出速率快于市售胶囊。结论:半固体骨架技术能够提高难溶性药物黄豆苷元的体外溶出度。     

熊果酸液固压缩片的制备及优势简

目的优选制备熊果酸液固压缩片的处方并探讨其优势。方法用不同处方制备熊果酸液固压缩片,同时与普通片剂进行片剂质量和溶出度比较。结果液固压缩片较普通片剂的溶出度大幅度提高,在45Min时最多可提高214％;片剂质量在崩解时限、重量差异等方面均明显优于普通片剂,崩解时限至少缩短一半。结论液固压缩技术可应用于难溶性药物熊果酸的制剂,且具有一定优势。     

盐酸依匹斯汀胶囊溶出度试验方法的建立及溶出曲线的评价

目的:建立盐酸依匹斯汀胶囊溶出度试验方法,并与市售产品进行溶出曲线评价,考察其有效性。方法:采用篮法,以水为溶出介质,转速为75 r·min-1,并对其与市售产品进行溶出曲线评价。溶出液色谱条件:色谱柱为Agilent Zorbax SB-CN柱(250 mm×4.6 mm,5μm);流动相为乙腈-0.05 mol.L-1磷酸盐缓冲溶液(35∶65);流速为1.0 mL·min-1;检测波长为220 nm;柱温为30℃。结果:盐酸依匹斯汀在0.10～24.12μg.mL-1范围内呈良好线性关系,r=0.999 9,因此采用此法检测本品溶出度,能达到要求,并且与市售产品溶出曲线相似。结论:溶出度的考察更能体现药品的有效性,该方法专属、灵敏、简便,可用于测定盐酸依匹斯汀胶囊的溶出度。     

布洛伪麻自微乳化制剂的处方筛选及体外溶出的评价

目的筛选布洛伪麻自微乳化释药系统处方,并考察其溶出度。方法通过绘制假三元相图、乳化后的外观及粒径的测定筛选最佳处方;以市售软胶囊为参比制剂测定自微乳化胶囊在不同溶出介质中的溶出度;考察自微乳化后药液的稳定性。结果最优处方为1,2-丙二醇、Tween80、油酸乙酯3种物质的质量比为15∶40∶45。自微乳化制剂中布洛芬在3种溶出介质中溶出无差异,45 min时溶出度均达80%以上,而市售软胶囊在蒸馏水、0.1 mol.L-1盐酸中,60 min布洛芬的溶出度不到40%。结论自微乳化制剂中布洛芬的溶出不受介质的影响。     

4种市售盐酸西替利嗪片剂的体外溶出度比较

目的通过测定4种市售盐酸西替利嗪片剂的溶出度,考察产品质量。方法采用转篮法测定溶出度,用威布尔(weibull)分布模型拟合溶出曲线,并对溶出参数m、T50、Td、T80进行方差分析。结果4种市售盐酸西替利嗪片剂的溶出参数m、T50、Td无显著性差异(P>0.05),T80A厂与C厂之间有显著性差异(P<0.05)。结论4种市售盐酸西替利嗪片剂的溶出度均符合规定。     

4种市售盐酸西替利嗪片剂的体外溶出度比较

目的通过测定4种市售盐酸西替利嗪片剂的溶出度,考察产品质量.方法采用转篮法测定溶出度,用威布尔(weibull)分布模型拟合溶出曲线,并对溶出参数m、T50 、Td、T80进行方差分析.结果 4种市售盐酸西替利嗪片剂的溶出参数m、T50 、Td无显著性差异(P>0.05), T80A厂与C厂之间有显著性差异(P<0.05).结论 4种市售盐酸西替利嗪片剂的溶出度均符合规定.     

液固压缩技术在药剂学中的应用

液固压缩技术是利用液体赋形剂溶解难溶性药物,然后用涂层材料吸收后得到固体粉末的一种技术。该技术可有效增加生物药剂学分类系统(BCS)Ⅱ类水难溶性药物溶出速率,通过液固压缩技术制得的粉末具有良好的流动性和可压性,工艺简单、成熟。重点介绍液固压缩技术的理论基础、作用机制和制备方法,并对液固压缩技术在难溶药物固体制剂和缓控释制剂中的应用进行归纳总结。     

Enhancement of famotidine dissolution rate through liquisolid tablets formulation: in vitro and in vivo evaluation

Although famotidine was reported to be 7.5 and 20 times more potent than ranitidine and cimetidine, respectively, its oral bioavailability is low and variable; due mainly to its poor aqueous solubility. The purpose of this study was to improve famotidine dissolution through its formulation into liquisolid systems and then to investigate the in vitro and in vivo performance of the prepared liquisolid tablets. The new mathematical model was utilized to formulate various liquisolid powder systems. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. All the tested liquisolid tablet formulations showed higher drug dissolution rates (DR) than the conventional, directly compressed tables. In addition, the selected optimal formula released 78.36% of its content during the first 10 min which is 39% higher than that of the directly compressed tablets. Further, the bioavailability study indicated that the prepared optimal liquisolid formula did not differ significantly from the marketed famotidine tablets concerning Cmax, tmax, and AUC(0-8) at P<0.05.     

Improvement of dissolution properties of Carbamazepine through application of the liquisolid tablet technique

The aim of the work was to improve the dissolution properties of the practically insoluble antiepileptic drug, Carbamazepine (CBZ) by adopting the liquisolid compaction technique. Reported liquid load factors, and excipient ratios were used to calculate the required amounts of excipients necessary to prepare the compacts or tablets according to a mathematical model. Avicel PH 102, and Aerosil 200 were used as the carrier and the coating materials, respectively, and explotab was used as disintegrant to prepare four tablet formulae, out of which formula 1 was successfully compressed into tablets. The dissolution patterns of liquisolid CBZ tablets, carried out according to the USP, were comparable to those of Tegretol^®. The protection of male albino mice against the convulsion, induced by electroshock, was lower in case of liquisolid tablets compared to Tegretol^® suspension and tablets probably due to the precipitation of CBZ in the silica pores resulting from its high dose.     

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.     

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.     

An investigation of physicochemical properties of piroxicam liquisolid compacts

The potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (piroxicam) was investigated. In this study, physicochemical properties of piroxicam liquisolid tablets, effect of aging, and type of the carrier were also investigated. To this end, several liquisolid tablets formulations containing various ratios of drug: solvent and different carriers were prepared. X-ray crystallography, differential scanning calorimetry (DSC), and contact angle measurement were used for evaluation of physicochemical properties of piroxicam. Liquisolid compacts exhibited significantly higher drug dissolution rates, in different dissolution media, than compacts prepared by the direct compression technique. The results showed that enhanced dissolution rate of piroxicam liquisolid tablets was due to an increase in wetting properties and surface area of drug available for dissolution. To investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the formulations were stored at 25 degrees C/75% relative humidity for 9 months. The results showed that aging had no significant effect on hardness or dissolution profile of liquisolid tablets. It was shown that Avicel had more liquid retention potential than other carriers, but there were no significant differences in the dissolution profiles between formulations. The results of DSC and X-ray crystallography did not show any changes in crystallinity of the drug and interaction between piroxicam and exipients (Avicel and silica) during the process.     

Effects of liquisolid formulations on dissolution of naproxen

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor^® EL (polyoxyl 35 castor oil), Synperonic^® PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel^® PH102 was used as a carrier material, Cab-o-sil^® M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor^® EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor^® EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised.     

Enhancement of dissolution rate of piroxicam using liquisolid compacts

Piroxicam is a poorly soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. There are several techniques to enhance the dissolution of poorly soluble drugs. Among them, the technique of liquisolid compacts is a promising technique towards such a novel aim. In this study, the dissolution behaviour of piroxicam from liquisolid compacts was investigated in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). To this end, several liquisolid tablets formulations containing various ratios of drug:Tween 80 (ranging from 10% to 50% w/w) were prepared. The ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was kept constant in all formulations. The results showed that liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made (capsules and directly compressed tablets containing micronized piroxicam). This was due to an increase in wetting properties and surface of drug available for dissolution.     

Liquisolid systems to improve the dissolution of furosemide

A liquisolid system has the ability to improve the dissolution properties of poorly water soluble drugs. Liquisolid compacts are flowing and compactable powdered forms of liquid medications. The aim of this study was to enhance the in vitro dissolution properties of the practically water insoluble loop diuretic furosemide, by utilising liquisolid technique. Several liquisolid tablets were prepared using microcrystalline cellulose (Avicel® pH-101) and fumed silica (Cab-O-Sil® M-5) as the carrier and coating materials, respectively. Polyoxy-ethylene-polyoxypropylene-polyoxyethylene block copolymer (Synperonic® PE/L 81); 1,2,3-propanetriol, homopolymer, (9Z)-9-octadecenoate (Caprol® PGE-860) and polyethylene glycol 400 (PEG 400) were used as non- volatile water-miscible liquid vehicles. The liquid loading factors for such liquid vehicles were calculated to obtain the optimum amounts of carrier and coating materials necessary to produce acceptable flowing and compactible powder admixtures viable to produce compacts. The ratio of carrier to coating material was kept constant in all formulations at 20 to 1. The formulated liquisolid tablets were evaluated for post compaction parameters such as weight variation, hardness, drug content uniformity, percentage friability and disintegration time. The in-vitro release characteristics of the drug from tablets formulated by direct compression (as reference) and liquisolid technique, were studied in two different dissolution media. Differential scanning calorimetry (DSC) and Fourier-Transform infrared spectroscopy (FT-IR) were performed. The results showed that all formulations exhibited higher percentage of drug dissolved in water (pH 6.4–6.6) compared to that at acidic medium (pH 1.2). Liquisolid compacts containing Synperonic® PE/L 81 demonstrated higher release rate at the different pH values. Formulations with PEG 400 displayed lower drug release rate, compared to conventional and liquisolid tablets. DSC and FT-IR indicated a possible interaction between furosemide and tablet excipients that could explain the dissolution results. Caprol® PGE-860, as a liquid vehicle, failed to produce furosemide liquisolid compacts.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets.

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.     

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.