红霉素肠溶微丸制备工艺

采用挤出—滚圆技术制备红霉素微丸丸芯，并用正交设计筛选其制备工艺；以甲基丙烯酸共聚物水分散体为包衣材料，建立微丸包衣数学模型指导包衣工艺。     

Iron oxide induced enhancement of mucoadhesive potential of Eudragit RLPO: formulation,evaluation and optimization of mucoadhesive drug delivery system

Objectives: The objective of the study was to investigate the effect of iron oxide in the development of mucoadhesive tablets of cinnarizine using Eudragit RLPO polymer. A simplex lattice design was employed for optimizing the drug delivery system.

Methods: Different concentrations of Eudragit RLPO (X₁), iron oxide (X₂) and PVP K 30 (X₃) were taken as independent variables and mucoadhesive strength, t_50%, t_90%, MDT and tablet tensile strength were the selected response variables. Contour and 3D plots were drawn to portray the relationship between independent and response variables. Ex vivo studies were performed for the determination of mucoadhesive strength of formulated tablets employing texture analyzer. ATR-FTR, DSC and zeta potential determination were conducted for drug-excipient and ionic interaction studies.

Results: Friability, hardness and tensile strength of mucoadhesive tablet formulation were found to be 0.42 ± 0.21%, 3.93 ± 1.57 kg/cm² and 0.65 ± 0.26 mN/m², respectively. Mucoadhesive strength was found to be ranging between 5.75 ± 4.41 and 42.85 ± 3.94 g. Value of release exponent (n) was found to be 0.65 ± 0.22, indicating anomalous drug release behavior from the formulations. Numerical optimization using the desirability approach was employed for developing optimized formulation by setting constraints of the dependent and independent variables. The mucoadhesive tablet formulation composition consisting of 8.58% w/w Eudragit RLPO, 7.02% w/w iron oxide and 7.26% w/w PVP K 30 fulfilled maximum requirements of an optimum formulation with better regulation of the selected constraints.

Conclusions: Eudragit RLPO and iron oxide combination showed high level potential for fabricating gastroretentive as well as mucoadhesive drug delivery systems.     

对乙酰氨基酚肠溶小丸片的制备工艺研究和质量考察

目的:考察衣膜材料、缓冲小丸的种类以及用量对肠溶型小丸片释药行为的影响。方法:以Eudragit NE30D和FS30D分别与Eudragit L30D-55以不同比例混合后,对含有对乙酰氨基酚的小丸进行包衣。包衣小丸分别与不同的辅料混合后压制成片剂,通过比较压片小丸和未压片小丸释药曲线的相似度(f2)值,来考察包衣膜材的延伸性。同时采用铸膜法制备与包衣处方相同的游离膜,并考察游离膜的机械性能。结果:Eudragit NE30D或Eudragit FS30D与Eudragit L30D-55以2∶1,1∶1和1∶2混合包衣小丸,压成片剂和未压成片的小丸的溶出曲线f2值分别为82,70,65和70,58,41,表明EudragitNE30D和Eudragit FS30D在加入一定量的Eudragit L30D-55后仍可以保护小丸压片时不破裂。采用不同材料制备的缓冲小丸,与包衣小丸混合压片,缓冲材料的种类对片剂的溶出曲线影响不大,主要是通过影响片剂的硬度和崩解时限而影响片剂的质量。结论:Eudragit NE30D和Eudragit FS30D均有着良好的延展性,添加Eudragit L30D-55后延展性变差...     

Preparation and in vitro evaluation of mebeverine HCl colon-targeted drug delivery system

Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.     

增塑剂及膜材比例对Eudragit L100/S100游离膜机械性能和透湿性的影响

采用平面铸膜法制备对pH敏感、可用于结肠定位的Eudragit L100/S100游离膜,并考察成膜湿度、增塑剂的种类与用量及膜材的比例对游离膜的影响。以膜的透湿性、机械性能为指标设计正交实验,优选出最佳的成膜处方,并研究其相关特性。结果表明,以柠檬酸三乙酯为增塑剂且含量为30%时,膜的机械性能和成膜性最好;膜材比例变化对游离膜的机械性能和透湿性影响不大。通过调整增塑剂的种类、用量及Eudragit L100/S100配比,可以制得符合结肠定位释放要求的游离膜。     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

Quantification of the types of water in Eudragit RLPO polymer and the kinetics of water loss using FTIR

Coalescence of polymer particles in polymer matrix tablets influences drug release. The literature has emphasized that coalescence occurs above the glass transition temperature (T_g) of the polymer and that water may plasticize (lower T_g) the polymer. However, we have shown previously that nonplasticizing water also influences coalescence of Eudragit RLPO; so there is a need to quantify the different types of water in Eudragit RLPO. The purpose of this study was to distinguish the types of water present in Eudragit RLPO polymer and to investigate the water loss kinetics for these different types of water. Eudragit RLPO was stored in tightly closed chambers at various relative humidities (0, 33, 56, 75, and 94%) until equilibrium was reached. Fourier transform infrared spectroscopy (FTIR)-DRIFTS was used to investigate molecular interactions between water and polymer, and water loss over time. Using a curve fitting procedure, the water region (3100–3700 cm⁻¹) of the spectra was analyzed, and used to identify water present in differing environments in the polymer and to determine the water loss kinetics upon purging the sample with dry compressed air. It was found that four environments can be differentiated (dipole interaction of water with quaternary ammonium groups, water cluster, and water indirectly and directly binding to the carbonyl groups of the polymer) but it was not possible to distinguish whether the different types of water were lost at different rates. It is suggested that water is trapped in the polymer in different forms and this should be considered when investigating coalescence of polymer matrices.     

Polyethylene glycol as an alternative polymer solvent for nanoparticle preparation

Solvent toxicity is one of the major drawbacks in the preparation of polymeric nanoparticles today. Here, polyethylene glycols (PEGs) are proposed as non-toxic solvents for the preparation of polymeric nanoparticles. Based on a preparation process similar to the solvent displacement technique, several process parameters were examined for their effects on the properties of the prepared nanoparticles by this method to achieve the optimum preparation conditions. The investigated parameters included polymer type and concentration, volume and temperature of the dispersing phase, methods of dispersing the solvent phase into the non-solvent phase, duration and speed of stirring and washing by dialysis. Ammonio methacrylate copolymer (Eudragit RL), poly-lactide-co-glycolide (PLGA), and PEG-PLGA were found to be successful polymer candidates for the preparation of nanoparticles by this method. Nanoparticles with diameters ranging from 80 to 400 nm can be obtained. The encapsulation efficiencies of bovine serum albumin, and lysozyme as model proteins were ranging from 7.3 ± 2.2% to 69.3 ± 1.8% depending on the strength of polymer–protein interaction. Biological assays confirmed a full lysozyme activity after the preparation process. PEG proved to be a suitable non-toxic solvent for the preparation of polymeric protein-loaded nanoparticles, maintaining the integrity of protein.     

Fast and pH-dependent release of domperidone from orally disintegrating tablets

There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug–polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10?min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation.     

Preparation of Indapamide slow-release pellets

During the process of developing a slow-release formulation of indapamide, researchers created a drug-containing pellet coated with Eudragit RS100 (Rohm GMbH & Co. KG, Darmstadt, Germany) to control the rate at which the drug was released. The two main variables were the agglomerants used in the pellet preparation and the amount of Eudragit RS100 used to coat them. The optimal outcome was indicated by the greatest number of drug-containing pellets recovered through an 18- to 24-mesh sieve and a satisfactory 24-hour release curve. The kinetics of dissolution fit the Higuchi kinetics model. Stability tests of the drug pellets showed no notable changes in the rate of drug release, related substances (mean byproducts or impurities from interactions or decompositions), and drug content.