Comparative studies with Kollicoat MAE 30 D and Kollicoat MAE 30 DP in aqueous spray dispersions and enteric coatings on highly swellable caffeine cores

A film formulation containing Kollicoat MAE 30 D, Kollidon 30, Sicovit Rot 30, titanium dioxide, talc, and a plasticizer for the aqueous manufacture of enteric coatings was studied for the coagulations occurring with certain plasticizers and for differences in resistance on highly swellable caffeine cores. Also included in these investigations were the latices Kollicoat MAE 30 DP and Eudragit L 30 D-55. The coagulations occurring with all three film latices can be attributed to the presence of Kollidon 30 together with certain excipients. Preparations with Kollidon 30, but without color pigments, showed no tendency to coagulate. The advantage of propylene glycol (PG) compared to other plasticizers such as triethyl citrate (TEC) is that no coagulations occurred, even in the presence of Kollidon 30 and color pigments. Among the Kollidon 30-free film formulations examined, a plasticizer content of 10-15% PG or TEC gave the best results. Optimal pigment distribution in the coat originally produced by Kollidon 30 can optionally be achieved by prolonged stirring of the pigment suspension. The resistance can be further improved by inclusion of a subcoating with Kollidon VA 64. Kollicoat MAE 30 D and MAE 30 DP and Eudragit L 30 D-55 showed identical behavior in this study.     

Comparative Studies with Kollicoat MAE 30 D and Kollicoat MAE 30 DP in Aqueous Spray Dispersions and Enteric Coatings on Highly Swellable Caffeine Cores

A film formulation containing Kollicoat MAE 30 D, Kollidon 30, Sicovit Rot 30, titanium dioxide, talc, and a plasticizer for the aqueous manufacture of enteric coatings was studied for the coagulations occurring with certain plasticizers and for differences in resistance on highly swellable caffeine cores. Also included in these investigations were the latices Kollicoat MAE 30 DP and Eudragit L 30 D-55. The coagulations occurring with all three film latices can be attributed to the presence of Kollidon 30 together with certain excipients. Preparations with Kollidon 30, but without color pigments, showed no tendency to coagulate. The advantage of propylene glycol (PG) compared to other plasticizers such as triethyl citrate (TEC) is that no coagulations occurred, even in the presence of Kollidon 30 and color pigments. Among the Kollidon 30–free film formulations examined, a plasticizer content of 10–15% PG or TEC gave the best results. Optimal pigment distribution in the coat originally produced by Kollidon 30 can optionally be achieved by prolonged stirring of the pigment suspension. The resistance can be further improved by inclusion of a subcoating with Kollidon VA 64. Kollicoat MAE 30 D and MAE 30 DP and Eudragit L 30 D-55 showed identical behavior in this study.     

Studies Comparing Kollicoat MAE 30 D with Commercial Cellulose Derivatives for Enteric Coating on Caffeine Cores

Abstract

The products that are processed in aqueous form, such as Aqoat MF (suspension), Aquateric (pseudolatex), HP 55 (ammonia-based solution), and Kollicoat MAE 30 D (latex), were compared (in the form of spray dispersions, isolated films prepared from the dispersions, and caffeine-film-coated tablets with 5.5, 8.0, and 11.0 mg film/cm²) with one another and with ethanolic HP 55 S solution. The addition of pigments to all of the liquid preparations, with the exception of the ammoniacal solution of HP 55, led to a slight increase in pH. In each case, the viscosity of both solutions was well above that of the other formulations. The minimum film-forming temperature was decidedly reduced by the addition of pigment. Kollicoat MAE was the undissolved film-former that had the smallest particle size and particle size distribution. The next smallest were those of Aqoat MF. The latex and the suspension were the only products that were sensitive to shear and heat. The isolated films did not display any tack. The strongest films and the films most impermeable to water vapor were obtained from solutions, and this can be ascribed to the fine distribution of the film-former. None of the isolated films showed signs of dissolving at pH 4.5. At pH 5.5, only the HP 55 was dissolved. This was because HP 55 was processed in ammonia-based solution; as a result of which, films that were not very resistant to gastric juice were obtained. The other formulations did not dissolve until the pH reached 6.0. As the pH rose, the rate of dissolution increased for all of the films. The permeability to protons was similar to that of caffeine-film-coated tablets to gastric juice. The resistance increased in the following sequence: HP 55 (ammonia-based) < Aquateric < Aqoat MF < HP 55 S (organic) and Kollicoat MAE.     

Variation of composition of an enteric formulation based on Kollicoat MAE 30 D

Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.     

Preparation and antibiotic drug release of mineralized collagen coatings on titanium

In this study, a mineralized collagen coating was electrolytically deposited onto titanium. The results showed that the mineralized collagen coatings with dense or porous morphology could be obtained. The mineral phase was mainly hydroxyapatite. In vitro evaluation showed the mineralized collagen coatings were stable in Kokubo’s simulated body fluid, and displayed a good cytocompatibility in the cell multiplication test. The mineralized collagen coatings loaded with vancomycin hydrochloride showed an inhibitory effect on the growth of S. aureus. The present mineralized collagen coating demonstrates good suitability for surface modification of orthopedic metal implants.     

Influence of Eudragit NE 30 D blended with Eudragit L 30 D-55 on the release of phenylpropanolamine hydrochloride from coated pellets

The objective of this study was to investigate the influence of Eudragit® NE 30 D blended with Eudragit® L 30 D-55 on the release of phenylpropanolamine hydrochloride (PPA·HCl) from coated pellets. The miscibility of Eudragit NE 30 D/L 30 D-55 blends at different ratios was studied by using differential scanning calorimetry. The release of PPA·HCl from pellets coated with Eudragit NE 30 D alone and a Eudragit NE 30 D/L 30 D-55 blend, when stored at 40°C and 60°C, was determined by UV spectroscopy. Eudragit NE 30 D and Eudragit L 30 D-55 were miscible in ratios greater than 4:1. The curing time that was required to reach an equilibrium state decreased with the addition of Eudragit L 30 D-55. The presence of Eudragit L 30 D-55 also produced a film coating that was less tacky, and a dispersion of Eudragit NE 30 D containing Eudragit L 30 D-55 (5:1) was shown to prevent agglomeration of the pellets during coating and storage.     

Studies on the stability and kinetics of drug release of dexamethasone phosphate intercalated layered double hydroxides nanohybrids

We report the intercalation of dexamethasone sodium phosphate drug in Mg/Al layered double hydroxides (LDHs) through co-precipitation technique. The as-synthesized nanohybrid was characterized by XRD, FTIR and thermal analysis techniques, which reveal that the dexamethasone phosphate anions are accommodated within the brucite layers. The shifting in the stretching frequency of phosphate anion of the drug provides strong evidence that the drugs are bonded to LDHs through electrostatic force. The surface charge analysis suggested the possibility of charge manipulation in LDHs system by varying intercalated anions. In-vitro release study of as-synthesized nanohybrid particles suggests a significant reduction in release rate of dexamethasone phosphate anions from Mg/Al–Dexa LDHs and is due to confinement of drugs in the interlayer. The mechanism of drugs diffusion in nanohybrid is studied by using dissolution–diffusion kinetic model, which reveals that it is probably due to dissolution and intra-particle diffusion of anions in the physiological medium.     

Influences of copolymers (Copovidone,Eudragit RL PO and Kollicoat MAE 30 DP) on stability and bioactivity of spray-dried and freeze-dried lysozyme

Protein stability is the most crucial factor in protein pharmaceutical preparations. Various techniques were applied for producing stable protein formulations such as spray-drying and freeze-drying. However, heating and freezing stresses are disadvantages for proteins using these methods, respectively. Accordingly, excipients have been used to preserve therapeutic effects of proteins during processing and for long period of time. Therefore, influences of Copovidone, Eudragit^® RL-PO and Kollicoat^® MAE-30 DP (as excipients) on stability and integrity of lysozyme (as a model protein) in spray-dried and freeze-dried forms were investigated. Protein formulations in both dried forms were prepared without and with the addition of mentioned excipients at different concentrations. Protein formulations were characterized for yield determination, morphology using scanning electron microscopic (SEM), thermal analysis by Differential Scanning Calorimetry (DSC), secondary structure stability using Fourier transform infrared (FT-IR) spectroscopy and biological activity. All protein formulations were subjected to a stability study as solid protein formulations for 3 weeks at 24?°C/76% relative humidity and aqueous protein samples were stored at 50?°C for 30?min in a water bath. Results showed that Copovidone successfully preserved integrity and biological activity of lysozyme before and after storage in both spray-dried and freeze-dried forms with more advantage for using higher concentration of the same excipient. Smooth spheres of spray-dried lysozyme formulations with Copovidone were smaller than spray-dried lysozyme without and with Kollicoat^® MAE-30 DP, which affected %yield produced. Copovidone has demonstrated valuable protection ability for lysozyme.     

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank’s solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank’s solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.     

载药壳聚糖缓释微球的制备及其释放研究

实验采用乳化交联法,使用复合交联剂(先用甲醛交联,再用戊二醛交联),制得盐酸四环素壳聚糖缓释微球,并考察不同分子量的壳聚糖、原料质量比、交联剂用量、复合交联剂用量、搅拌速度对微球的影响,筛选出最佳条件制备出戢药微球,并研究了该微球在扫描电镜和倒置式研究型显微镜下的形态及其在pH=7.4,温度为37℃时的释放规律.结果表明,采用复合交联剂的乳化交联法所制得的微球球形好,粒径分布为5～50μm之间,载药量为26.9%,包封率为56.3%,并且具有良好的缓释效果.     

In vitro drug release study of methacrylate polymer blend system: effect of polymer blend composition,drug loading and solubilizing surfactants on drug release

The application of polymers as the drug delivery systems for treating oral infections is a relatively new area of research. The present study was to test the release of the antibacterial drug chlorhexidine diacetate (CHDA), the antifungal drug Nystatin (NYS) and the antiviral drug acyclovir (ACY) from polymer blends of poly(ethyl methacrylate) and poly(n-hexyl methacrylate) of different compositions. The effects of polymer blend composition, drug loading and solubilizing surfactants on the release of the drugs have been studied. Measurements of the in vitro rate of drug release showed a sustained release of drug over extended periods of time. Drug release rates decreased with increasing PEMA content in polymer blends. CHDA release rates increased steadily with increasing drug load. The drug release rates increased with the addition of surfactants. This study demonstrates that the three therapeutic agents show a sustained rate of drug release from polymer blends of PEMA and PHMA over extended periods of time. By varying polymer blend compositions as well as the drug concentration (loading), it is possible to control the drug release rates to a desired value. The drug release rate is enhanced by addition of surfactants that solubilize drugs in the polymer blends.     

Effect of diluents on tablet integrity and controlled drug release

The objective of this study was to evaluate the effect of diluents and wax level on tablet integrity during heat treatment and dissolution for sustained-release formulations and the resultant effect on drug release. Dibasic calcium phosphate dihydrate (DCPD), microcrystalline cellulose (MCC), and lactose were evaluated for their effect on tablet integrity during drug dissolution and heat treatment in wax matrix formulations. A newly developed direct compression diluent, dibasic calcium phosphate anhydrous (DCPA), was also evaluated. Compritol® 888 ATO was used as the wax matrix material, with phenylpropanolamine hydrochloride (PPA) as a model drug. Tablets were made by direct compression and then subjected to heat treatment at 80°C for 30 min. The results showed that MCC, lactose, and DCPA could maintain tablets intact during heat treatment above the melting point of wax (70°C-75°C). However, DCPD tablets showed wax egress during the treatment. MCC tablets swelled and cracked during drug dissolution and resulted in quick release. DCPD and lactose tablets remained intact during dissolution and gave slower release than MCC tablets. DCPA tablets without heat treatment disintegrated very quickly and showed immediate release. In contrast, heat-treated DCPA tablets remained intact through the 24-hr dissolution test and only released about 80% PPA at 6 hr. In the investigation of wax level, DCPD was used as the diluent. The drug release rate decreased as the wax content increased from 15% to 81.25%. The dissolution data were best described by the Higuchi square-root-of-time model. Diluents showed various effects during heat treatment and drug dissolution. The integrity of the tablets was related to the drug release rate. Heat treatment retarded drug release if there was no wax egress.     

Controlled release of drug from folate-decorated and graphene mediated drug delivery system: Synthesis,loading efficiency,and drug release response

A novel folate-decorated and graphene mediated drug delivery system was prepared that involves uniquely combining graphene oxide (GO) with anticancer drug for controlled drug release. The nanocarrier system was synthesized by attaching doxorubicin (DOX) to graphene oxide via strong π–π stacking interaction, followed by encapsulation of graphene oxide with folic acid conjugated chitosan. The π–π stacking interaction, simplified as a non-covalent type of functionalization, enables high drug loading and subsequent controlled release of the drug. The encapsulated graphene oxide enhanced the stability of the nanocarrier system in aqueous medium because of the hydrophilicity and cationic nature of chitosan. The loading and release of DOX indicated strong pH dependence and imply hydrogen-bonding interaction between graphene oxide and DOX. The proposed strategy is advantageous in terms of targeted drug delivery and has high potential to address the current challenges in drug delivery. Thus, the prepared nanohybrid system offers a novel formulation that combines the unique properties of a biodegradable material, chitosan, and graphene oxide for biomedical applications.     

星形两亲性嵌段共聚物的自组装及其药物控释行为研究

考察了星形两亲性嵌段共聚物-C(CH2OCOCH2- PS80-b-PDMA111)4在选择性溶剂中的自组装过程,通过DLS研究了嵌段共聚物组装成胶束的粒径及粒径分布,并采用TEM观察了胶束的形貌.研究了在不同的pH条件下,胶束粒径随温度的升高而变化的现象;以及胶束在去离子水及pH=10的缓冲溶液中对CLB的控制释放行为.结果发现:嵌段共聚物在选择性溶剂中可自组装成粒径均匀的球形聚集结构,粒径在406nm左右,粒径分布为0.113;在pH=10的缓冲溶液中,胶束浓度较小时,粒径随温度的升高而减小,而浓度较大时胶束粒径则会增加并发生胶束间的聚集直至沉淀析出;在去离子水中,胶束能够有效地加载药物并能延长药物的释放时间.     

Effect of core size and excipients on the lag time and drug release from a pulsatile drug delivery system

Background: Pulsatile drug delivery system, based on a core-in-cup dry-coated tablet was examined and evaluated. The system consisted of three different parts: a core tablet (with increasing diameter), containing the active ingredient acting as reservoir; an impermeable outer shell; and a top cover layer barrier. The core tablet contained either caffeine or theophylline as model drugs. Objective: To investigate and evaluate how the geometrical characteristics of the core tablets, drugs, and excipients influence the behavior of the system presented, namely, lag time and drug release. Results and Discussion: Drug release exhibited a lag time period dependent on the core tablet size, drug solubility, and characteristics of polymer and polymer mixtures. The lag time was increased by increasing the core tablet diameter and the quantity of soluble lactose in the top cover layer. Conclusions: The quantity and characteristics of materials, the core tablet size, and the erosion of the top cover layer were found to be important factors in controlling the lag time and release. Increase in core tablet diameter resulted in lower lag times and greater release and release rates. Similarly, by increasing sufficiently the quantity of the soluble excipient lactose, in the top layer we observed a decrease of the lag times and an increase of release.     

屏蔽层对支架涂层药物缓释影响的体外研究

载药涂层的药物释放行为对于药物洗脱支架的临床治疗效果具有非常重要的意义。讨论了在聚碳酸酯载药涂层外面再加一层空白聚合物层(即屏蔽层)对药物释放的影响。从4方面的体外实验证明屏蔽层(drug free polymer layer,DFPL)可以防止聚碳酸酯载药涂层药物"暴释"的现象,并且屏蔽层厚度和释放速率不是简单的比例关系,以及不同的药物梯度和不同的屏蔽层材料对药物释放有不同的影响效果。     

Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug

Abstract

This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol–gel–sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer–Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium.     

氧化还原响应型树枝状大分子的制备及释药性能研究

以乙二胺(EDA)、丙烯酸甲酯(MA)、聚乙二醇单甲醚-1900(mPEG-1900)、胱胺二盐酸盐为原料合成两亲树枝状大分子体系(mPEG-G4.0,mPEG-G(S—S)3.0,mPEG-G(S—S)4.0),通过傅里叶红外(FT-IR)确定聚合物的结构,以阿霉素(DOX)为模型分子研究该药物载体的包载和药物释放情况,获得树状大分子的特点、性质及对氧化还原的敏感性。结果表明mPEG-G4.0胶束、mPEG-G(S—S)3.0胶束、mPEG-G(S—S)4.0胶束的粒径均在670nm以下,且均具有良好的药物包载性能。载有DOX的mPEG-G(S—S)3.0,mPEG-G(S—S)4.0胶束在高的浓度GSH条件下药物释放速度较快,具有显著的氧化还原敏感性。     

海藻酸钠-胰蛋白酶微球的制备及药物释放性能

通过离子凝胶法制备出球形完好的海藻酸钠-胰蛋白酶微球.红外分析表明,微球中凝胶基质通过海藻酸钠的-COO-与Ca2+发生静电作用交联形成.SEM观察显示微球中存在蛋格结构及孔洞.考察了不同因素对微球载药率、包封率和体外释药率的影响.结果表明,海藻酸钠水溶液浓度越高释药率越低,当海藻酸钠与胰蛋白酶质量比为4,海藻酸钠水溶...     

Release behaviors of drug loaded chitosan/calcium phosphate coatings on titanium

Implants with antibiotic drug loaded bioactive coatings have been increasingly applied in orthopedic operations. Here we report the drug release behavior of gentamycin loaded chitosan/calcium phosphate coatings on titanium. Chitosan/calcium phosphate coatings with different component ratios and surface topographies were prepared by electrochemical deposition method. Our results showed that the drug release from these coatings was controlled by their component ratio and surface topography, and the former ratio played a more significant role. The present coatings could provide an effective way to create both good bioactivity and antibacterial activity.