Effect of particle morphology and pore size on the release kinetics of ephedrine from mesoporous MCM-41 materials

Ephedrine was loaded onto siliceous mesoporous materials of different pore sizes, and the corresponding drug release into simulated body fluid at pH 7.4 and 37?°C was measured against time over a period of 72?h. The mesoporous materials designated MCM-41(C_N) were prepared at different pore sizes using a self-assembly mechanism. The pore size was controlled by the use of alkyltrimethylammonium bromide (C_NTAB) surfactants having different alkyl chain lengths (C₁₀, C₁₂, and C₁₄). The three mesoporous materials showed good ephedrine-loading capacities from dry ethanolic solutions, which slightly increased with the pore size of MCM-41(C_N). From the drug release profiles, the overall release of ephedrine followed the order: MCM-41(C₁₂)?>?MCM-41(C₁₄)?>?MCM-41(C₁₀), with the release of ephedrine attaining 92% of the drug load from MCM-41(C₁₂). Ephedrine release approached 60% of the drug load in 6?h and 92% in 20?h. The results of in vitro release kinetics indicate that pore size is not the only factor affecting ephedrine release, but also pore channel length and overall particle morphology.     

Ibuprofen release from porous hydroxyapatite tablets

The present study investigated drug release profiles from porous hydroxyapatite [Ca₅(PO₄)₃OH, HAP] tablets. HAP tablets prepared synthetically and porous structure was generated via microemulsion after sintering at 700 °C. The influence of tablet's microemulsion concentration on drug release profiles from sintered porous tablets was investigated by using ibuprofen (C₁₃H₁₈O₂) as model drug.A numerical approach based on Fick's second diffusion law was used to investigate drug release kinetics from porous HAP tablets. Via this equation, diffusion coefficients were calculated for each tablet and compared. Drug release from the tablets was influenced by the porosity and tortuosity of the porous network. The drug release from porous HAP tablets was increased by microemulsion concentration. It is possible to obtain HAP based drug delivery system which has different drug release behavior by controlling microemulsion concentration in tablets before sintering.     

Konjac glucomannan and xanthan gum as compression coat for colonic drug delivery:experimental and theoretical evaluations

Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan (KGM) and xanthan gum (XG) as the compression coat. Diffusion of cimetidine from compression coated tablets was investigated by release experiment in Vitro. 0.22U/mL β-mannanase was applied in the mimic colon solution. The structure of the mixture polysaccharide was studied by an atomic force microscope (AFM). The experimental results indicate that a KGM70 tablet with a 0.4 g coat is of good design, due to a less than 5% drug loss in the mimic upper gastrointestinal solution by the synergistic interaction between XG and KGM, and due to about 50% cumulative release in the mimic colon solution by degradation after 24 hours. The release mechanism and model are discussed based on different periods of drug release including the delay of the drug, the constant release without an enzyme and the delay of degradation. Under hydrolysis by β-mannanase, drug release from the tablet with KGM coat shows an exponential increase, while that from the dosage with the mixture polysaccharide coat is an approximately zero-order process in which the constant release rate relates to the release velocity of a non-degraded system, the content of KGM within the coat and the average molecular weight ratio of KGM to XG. It was found that XG was the framework of the polysaccharide mixtures by AFM, which is similar to the analysis results from experiments on drug release.     

Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix^® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise^®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix^® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.     

甲硝唑缓释片制备与药物释放

利用湿法造粒,制备了甲硝唑羟丙基甲基纤维素(HPMC)骨架缓释片。实验结果表明,提高HPMC质量分数与使用高粘度HPMC可有效降低释药速率,但粘度4 000 mPa.s以上HPMC释药速率的降低不明显;含有粒径较大的甲硝唑原药的片剂,由于药物较强的致孔作用,药物释放速率较高;由于表面积较小的键形片上,HPMC水化凝胶层面积相对较小,甲硝唑从键形片的释放快于表面积较大的圆形片的释放。HPMC粘度、药物颗粒粒径与片形对释药速率的影响都与药物的溶解度有关。机制分析表明,药物曲线的释放符合H iguch i方程。     

The synergistic cooperation between MCM-41 and azithromycin: a pH responsive system for drug adsorption and release

The capability of MCM-41 silica for accepting and delivering poorly soluble azithromycin (AZT) in water is reported as robust drug delivery system. This property has been evidenced by using two MCM-41 samples with different pore sizes as hosts of AZT. The choice of this macrolide antibiotic is due not only to its low bioavailability but also to its molecular size which lies in the range of pore diameter of MCM-41s. The drug was loaded inside the pore voids of the mesoporous when MCM-41 was stirred at AZT solution, based on XRD, Nitrogen adsorption–desorption isotherms, TGA analysis data and FT-IR spectroscopy. The amount of AZT stored inside the pores of MCM-41 s was between 22 and 25 wt%. The loaded drug was released in different rates from the particles by changing the pH (1.7 and 7.4) to give a smart pH-responsive carrier system. The drug release kinetics was fitted to Korsmeyer–Peppas and Higuchi models which indicated that the rate of drug release was controlled by the diffusion of the drug. The result of the present study confirms that the controlled adsorption and liberation of AZT may improve the oral bioavailability of poor water soluble AZT. This study demonstrates the feasibility of designing reliable drug delivery systems by appropriate choice of the matrix and the organic molecule. In general, MCM-41 is a promising matrix for AZT adsorption with different application from drug delivery to wastewater filtration.     

Development of mesoporous bioactive glass-containing macroporous titanium for controlled release of antimicrobial drugs

Biofilm-associated infections pose a serious threat to the long-term survival of metal-based bone implants, which can potentially be resolved by the controlled delivery of antimicrobial agents locally at the implant surface. Mesoporous bioactive glasses (BAGs) are multifunctional materials able to combine bone-bonding properties with such a drug release functionality. Here, we propose for the first time to modify a macroporous Ti implant material with an antimicrobial-releasing BAG phase. The feasibility of a sol-gel synthesis route, including the structure-directing agent (SDA) Pluronic F127, and its effect on the mesoporous structure and concomitant drug release performance was evaluated. Mesopore sizes ranged from 3.4 nm for SDA-free to 3.7 nm for SDA-derived BAG, thereby both enabling configurational diffusion of the antiseptic chlorhexidine (CHX), but the latter showed a more narrow pore size distribution leading to a slower, more controlled release. Adjusting the feed concentration allowed fine-tuning the daily CHX release through the SDA-derived Ti/BAG composite to 1.4 μM. Even though just below the biofilm inhibitory concentration, this daily release rate was sufficient to effectively prevent Streptococcus mutans biofilm formation on the surface of the material. This proof-of-concept for a temporary antimicrobial-releasing bioceramic surface modification on Ti can be of interest for orthopedic implants.     

Thermoreversible hydrogels. XII. Effect of the polymerization conditions on the swelling behavior of the N‐isopropylacrylamide gel

The swelling behavior for the poly(N‐isopropylacrylamide) (NIPAAm) hydrogel prepared in various conditions such as various polymerization media, i.e., deionized water, acetone, and ethanol aqueous solution, and different polymerization temperatures were investigated in this work. The gels were also assessed for suitability in drug‐controlled release. The results indicated that the swelling behavior of the gel was dependent on the polymerization media and temperature, that is, the swelling ratios of gel were related to the pore size and the looser or denser structure of the gel. In addition, the pore size of the gel could be controlled by adjusting the surrounding temperature. Hence, the gel can be used to deliver drugs with different sizes. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 1604–1611, 2000     

Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant

Two different types of ordered mesoporous nanoparticles, namely MCM-41 and MCM-48, with similar pore sizes but different pore connectivity, were loaded with aprepitant via a passive diffusion method. The percentage of the loaded active agent, along with the encapsulation efficiency, was evaluated using High-performance Liquid Chromatography (HPLC) analysis complemented by Thermogravimetric Analysis (TGA). The determination of the pore properties of the mesoporous particles before and after the drug loading revealed the presence of confined aprepitant in the pore structure of the particles, while Powder X-ray Diffractometry(pXRD), Differential Scanning Calorimetry (DSC), and FTIR experiments indicated that the drug is in an amorphous state. The release profiles of the drug from the two different mesoporous materials were studied in various release media and revealed an aprepitant release up to 45% when sink conditions are applied. The cytocompatibility of the silica nanoparticles was assessed in Caco-2 cell monolayers, in the presence and absence of the active agent, suggesting that they can be used as carriers of aprepitant without presenting any toxicity in vitro.     

Interzeolite Conversion of FAU Type Zeolite into CHA and its Application in NH3-SCR

In this work we studied the potential feasibility to synthesize small pore zeolites, such as chabazite (CHA) via interzeolite conversion of FAU type zeolite. We have thereafter used CHA as the starting material to obtain Cu–CHA. When CHA in NH₄ ⁺ form was used to prepare Cu–CHA, the large size of the potassium cation present in the structure caused pore blockage in the chabazite framework, and diminished the adsorption and exchange capacity. However, Cu–CHA with comparable Selective Catalytic Reduction performance to the commercial catalyst was obtained via ion exchange if Cu-exchange was performed from H⁺–CHA form. Still, the main challenge was to fully eliminate K⁺ from the zeolite structure in order to further improve its catalytic performance and high temperature stability.     

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs.     

Swelling behaviour and paracetamol release from poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide-itaconic acid) hydrogels

Copolymer hydrogels of N-isopropylacrylamide and itaconic acid (IA), crosslinked with N,N′-methylenebisacrylamide, were prepared by radical copolymerization. These hydrogels were investigated with regard to their composition to find materials with satisfactory swelling and drug release properties. A paracetamol is used as a model drug to investigate drug release profile of the hydrogels. It was found that the investigated hydrogels exhibited pH- and temperature-dependent swelling behaviour with restricted swelling and lower equilibrium degree of swelling at lower pH values and temperatures above the LCST value of PNIPAM (around 34 °C). The diffusion exponent for paracetamol release indicate that the mechanism of paracetamol release are governed by Fickian diffusion, while in all release media initial diffusion coefficient was lower than late time diffusion coefficient. Furthermore, the paracetamol release rate depends on the hydrogel degree of swelling and it increased in the first stage of diffusion process, whereas was no significant difference thereafter. The presence of the IA moieties incorporated into the network weakened the shear resistance of the hydrogels. In order to calculate the pore size the characteristic ratio for PNIPAM, C _n  = 11.7, was calculated. Based on the pore size, the investigated hydrogels can be regarded as microporous. According to the obtained results swelling behaviour, mechanical properties, drug-loading capacity and the drug release rate could be controlled by hydrogel composition and crosslinking density, which is important for application of the investigated hydrogels as drug delivery systems.     

Chitosan tablets for controlled release of theophylline: Effect of polymer—drug wet or dry blending and anionic—cationic interpolymer complex

Chitosan tablets containing theophylline were prepared by directly compressing the wet or dry blended polymer—drug powders. The effects of the viscosity and swelling ability on the release rates of drugs were examined. The theophylline releasing rates of tablets prepared by polymer—drug wet blending increase with a decrease in the viscosity of the blending chitosan solution. On the other hand, the swelling ability of the polymer greatly influences the release kinetics of the tablets prepared by polymer—drug dry blending. Tablets prepared by both polymer—drug wet and dry blending were acid-nonresisted. Tablets in simulated gastric fluid disintegrated quickly, and the drugs were released within four hours. To retard the disintegrated rate of chitosan tablets in acid medium, interpolymer complex of chitosan with anionic polyelectrolyte (alginate) is needed. By this treatment, the swelling and erosion rate of the chitosan tablets could be reduced, then controlling the release rate of the theophylline can be achieved. Drug release mechanism of the various tablets were investigated by the model of Peppas; in addition, a nuclear magnetic resonance imagine microscopy is also introduced to examine the swelling or diffusion mechanism of various tablets. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 2495–2505, 1997     

Statistical optimization and characterization of pH-independent extended-release drug delivery of cefpodoxime proxetil using Box–Behnken design

The aim of this study was to develop and optimize the pH-independent extended-release (ER) formulations of cefpodoxime proxetil (CP) using response surface methodology by employing a 3-factor, 3-level Box–Behnken statistical design. The independent variables studied were the amount of hydroxypropyl methylcellulose (HPMC K4M), sodium alginate (SA) and microcrystalline cellulose (MCC). The drug release percent at 2, 4, 8, 14 and 24 h were the target responses and were restricted to 15–30, 35–55, 55–75, 75–90 and 90–110%, respectively. The response surface methodology and multiple response optimizations utilizing a polynomial equation were used to search for the optimal formulation with a specific release rate at different time intervals. The results showed that the effect of combination of HPMC K4M and SA was the most influencing factor on the drug release from ER matrix tablets. The mechanism of drug release from ER tablets was dependent on the added amount of SA. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 25% HPMC, 15.14% SA, and 20.14% MCC was prepared according to the software determined levels. DSC and FTIR studies combined with the stability study of the optimized formulation proved the integrity of the developed formulation. The Box–Behnken experimental design facilitated the formulation and optimization of extended release hydrophilic matrix systems of CP in a short period of time and with the fewest number of experiments.     

Preparation and characterization of vancomycin releasing PHBV coated 45S5 Bioglass®-based glass–ceramic scaffolds for bone tissue engineering

Porous 45S5 Bioglass^®-based glass–ceramic scaffolds with high porosity (96%) and interconnected pore structure (average pore size 300 μm) were prepared by foam replication method. In order to improve the mechanical properties and to incorporate a drug release function, the scaffolds were coated with a drug loaded solution, consisting of PHBV and vancomycin. The mechanical properties of the scaffolds were significantly improved by the PHBV coating. The bioactivity of scaffolds upon immersion in SBF was maintained in PHBV coated scaffolds although the formation of hydroxyapatite was slightly retarded by the presence of the coating. The encapsulated drug in coated scaffolds was released in a sustained manner (99.9% in 6 days) as compared to the rapid release (99.5% in 3 days) of drug directly adsorbed on the uncoated scaffolds. The obtained drug loaded and bioactive composite scaffolds represent promising candidates for bone tissue engineering applications.     

DNJ双层渗透泵片的制备及比格犬体内药动学研究

制备了1-脱氧野尻霉素（DNJ）双层渗透泵片,以释放度为评价指标优化了处方,考察了DNJ双层渗透泵片的体外释药性,并对比研究了DNJ双层渗透泵片和速释片在比格犬体内的药动学。DNJ双层渗透泵片的最优处方为含药层羟丙基甲基纤维素（HPMC） E50用量为10 mg、助推层聚氧乙烯（PEO,M_r 6×10⁶）用量为80 mg 、包衣层醋酸纤维素（CA）用量为15 mg及聚乙二醇（PEG）4000用量为5 mg,在此条件下DNJ溶出速度最为适宜,并且不受pH值的变化影响,药物12 h溶出完全,且恒速缓慢释放。对比DNJ双层渗透泵片和速释片在比格犬体内的双制剂双周期交叉试验,结果表明：双层渗透泵片释放的达峰时间（t_max）为（9.3±3.8）h比速释片（4.4±2.2）h显著延迟,达到了缓控释的目的,渗透泵片的相对生物利用度为（96.1±9.8）%,90%置信区间为84.8%~103.7%,渗透泵片与速释片吸收程度生物等效。     

酸化凹凸棒石/海藻酸复合材料的制备及其缓释性能

以海藻酸钠 (SA) 和酸化凹凸棒石 (H⁺-ATP) 为原料,运用溶液共混法制备了一种具有优良缓释性能的复合材料,并以其为基质材料制备了双氯芬酸钠 (DS) 缓释片.利用SEM、FTIR和XRD对复合材料形貌和结构进行了表征,考察了酸改性剂浓度、H⁺-ATP用量和复合时间对复合材料缓释性能的影响,以获得最佳复合工艺.结果表明,当用12 mol·L^-1盐酸酸化的ATP量占复合物总量60%时,复合缓释片在体外模拟肠液中缓释性能最佳.与单一海藻酸缓释片相比,复合缓释片2 h的累积释放率由42.6%下降到23.7%,有效改善了"突释"效应.释放动力学研究表明,复合缓释片的释药行为可以用Ritger-Peppas方程很好地拟合,释药速率受骨架溶蚀和药物扩散双重控制.H⁺-ATP的加入显著改善了海藻酸的缓释性能.     

Application of PDMS-based coating in drug delivery systems using PVP as channeling agent

PDMS derivatives have been extensively used as coating in controlled drug delivery systems in pharmaceutical area. The major advantages of these materials are facilitation of adjustment of desired drug release patterns, improvement of film formation and storage stability. In this study PDMS-based coating systems were designed and applied to acetaminophen tablets and their release was investigated from the PDMS-coated tablet dosage form as a drug model. Thus, a water emulsion of PDMS containing tetraethoxysilane as cross-linking agent and polyvinylpyrrolidone (PVP) as channeling agent was prepared. Then, a uniform smooth thin coating of PDMS was applied on acetaminophen tablets and in vitro acetaminophen release from PDMS-coated tablets was carried out with a homemade setup. The morphology of the coated surfaces was studied by SEM technique. The effect of PVP on the mechanical properties of PDMS film was investigated by dynamic mechanical analysis. It was found that, PVP increased the mechanical properties of PDMS. Compounding of polyethylene glycol (PEG) with PVP (1:1) as channeling agents was also studied and compared with PVPs-containing samples. Despite more channeling agent content in PEG–PVP samples, the drug release percentage was decreased.     

Effects of drying process for amorphous waxy maize starch on theophylline release from starch‐based tablets

Physical properties and theophylline‐release profiles of compressed tablets prepared with amorphous waxy maize starches dried using different methods were examined. A gelatinized waxy maize starch paste (10% solids in water) was either freeze‐dried or oven‐dried (40 or 105°C) until the moisture content reached to <5%. To form the tablets, the dried amorphous starch powders, either with or without theophylline (3 : 10, w/w), were remoistened to a water content of (17 ± 0.2)%, and compressed into tablets. The drying process applied to the amorphous starch powders affected both the compactness and swelling behavior of the tablets. Although no crystallinity was detected in all the starches tested, X‐ray diffraction patterns indicated that starch chains dried at the lower temperature (40°C) are allowed more time to re‐associate during the drying process than those dried at the higher temperature (105°C). The freeze‐dried starch powders formed tablets characterized by greater compactness and rigidity than was observed in the oven‐dried starch samples. The drug release of the tablets prepared with the starch dried at the higher temperature (105°C) occurred at a much slower rate than that of the tablets made with the starch dried at the lower temperature (40°C). The drug release characteristics of the freeze‐dried starch tablets were nearly identical to those of the tablets prepared with the starch dried at 105°C. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

新藤黄酸亲水凝胶骨架缓释片的处方工艺研究

研制新藤黄酸亲水凝胶骨架缓释片并初步建立含量测定的方法.采用正交设计法,以崩解时间、缓释效果和pH值为指标综合评价筛选处方,用高效液相法测定制剂的含量.最佳处方为A2B2C3D1,即羟丙甲基纤维素K15M、乙基纤维素、乳糖的用量分别占片重的30%、6%、15%.高效液相法测定新藤黄酸含量在5.0-25.0μg/mL,线性良好.