Sustained-release from layered matrix system comprising chitosan and xanthan gum

Sustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH₃⁺ of chitosan molecule and COO^- of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.     

黄原胶及其应用

黄原胶是一种生物高分子,广泛应用于３０多个行业。综述了黄原胶的生物化学、发酵工艺、产品后处理及其应用等方面的进展。     

Preparation and In Vitro Characteristics of Lactoferrin-loaded Chitosan Microparticles

ABSTRACT

In order to achieve the delivery and controlled release of lactoferrin (LF), a biologically multifunctional protein, chitosan microparticles loaded with LF were prepared. Several types of chitosan microparticles containing LF were prepared by the w/o emulsification-solvent evaporation method, and the particle characteristics and release properties in JP 2nd fluid, pH 6.8, were examined. All kinds of microparticles were obtained at a yield of more than 75% (w/w). LF-loaded microparticles prepared by nonsonication and nonaddition of sulfate, named Ch-LF(N), showed high drug content, small particle size and spherical particle shape. Also, for release properties, Ch-LF(N) exhibited gradual drug release over 7 hr with less remaining in the microparticles. Considering the mucoadhesive properties of chitosan microparticles, Ch-LF(N) are suggested to be useful for gradual supply to topical diseased sites or for effective delivery to intestinal areas with abundant LF receptors.     

耐热性黄原胶的制备与性能

油田油藏条件下使用的黄原胶在高温下易发生降解、黏度下降。文中研究了除氧剂(硫代硫酸钠)对黄原胶耐热稳定性的影响,结果表明,当硫代硫酸钠的使用浓度为1.5 g/L时,黄原胶溶液经121℃高温处理3 h,其黏度下降幅度变小,黏度保留率得到明显的提高,耐热稳定性提高了1.85倍。通过包埋硫代硫酸钠,制备出了具有较高耐热性的黄原胶。采用热重分析仪(TGA)对其耐热性进行了研究,研究表明,黄原胶(包埋硫代硫酸钠)的耐热稳定性得到有效的改善。     

Release of pentoxifylline from xanthan gum matrix tablets

Pentoxifylline-controlled release tablets were prepared using xanthan gum. The effects of polymer concentration, rotation speed, ionic strength, and pH of the dissolution medium on the release of the water-soluble pentoxifylline were studied. The release rate decreased with increasing polymer concentration in the tablet, which was reflected in the increase in the mean dissolution time. A higher rotation speed and increased ionic strength of the dissolution medium resulted in a higher rate of drug release of xanthan-based tablets. A higher release rate of pentoxifylline was also observed using acidic dissolution medium.     

Preparation and In Vitro Evaluation of Chitosan Microspheres Containing Prednisolone: Comparison of Simple and Conjugate Microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Ketoprofen Suppository Dosage Forms: In Vitro Release and in Vivo Absorption Studies in Rabbits

In vitro release of ketoprofen from suppository bases and in vivo absorption in rabbits were studied. Suppositories containing 50 mg of ketoprofen were prepared using theobroma oil, esterified (c₁₀–c₁₈) fatty acids, and polyethylene glycol 1000 bases. The displacement values of the drug were determined and found to be of the order of theobroma oil > esterified (c₁₀–c₁₈) fatty acids and polyethylene glycol 1000 bases. The suppository hardness data revealed that the theobroma oil base produced relatively brittle suppositories. Using the USP dissolution method, the release of ketoprofen was observed to be greatest from polyethylene glycol 1000 suppositories. With the dialysis technique, the maximum release of drug was obtained from theobroma oil suppository containing polysorbate 40 at a 6% level. Selected suppository formulations were evaluated for rectal absorption studies in rabbits. The in vivo data showed that the optimum drug absorption took place from the polyethylene glycol 1000 base and theobroma oil formulation containing 6% polysorbate 40.     

Possible Mechanism for Drug Retardation from Glyceryl Monostearate Matrix System

Lipophilicity was evaluated as a possible mechanism for drug retardation from a glyceryl monostearate matrix system. Lipophilicity of the glyceryl monostearate matrix system was studied using contact angle measurement of water droplets on the surface of compressed disks, extrudate ascension of water, and movement of water through a powder mixture packed in a high-performance liquid chromatographic (HPLC) column. Increase in glyceryl monostearate content resulted in an increase in water droplet contact angle, decrease in the rate of water ascending the extrudate, and increase in the pressure values as a function of flow rate of water moving through the powder mixture. These could be due to the increase in lipophilicity of the matrix, rendering the matrix less wettable. As a result, the rate of water penetration into the matrix decreased, and the drug release could be sustained.     

Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.     

Preparation and in vitro characteristics of lactoferrin-loaded chitosan microparticles

In order to achieve the delivery and controlled release of lactoferrin (LF), a biologically multifunctional protein, chitosan microparticles loaded with LF were prepared. Several types of chitosan microparticles containing LF were prepared by the w/o emulsification-solvent evaporation method, and the particle characteristics and release properties in JP 2nd fluid, pH 6.8, were examined. All kinds of microparticles were obtained at a yield of more than 75% (w/w). LF-loaded microparticles prepared by nonsonication and nonaddition of sulfate, named Ch-LF(N), showed high drug content, small particle size and spherical particle shape. Also, for release properties, Ch-LF(N) exhibited gradual drug release over 7 hr with less remaining in the microparticles. Considering the mucoadhesive properties of chitosan microparticles, Ch-LF(N) are suggested to be useful for gradual supply to topical diseased sites or for effective delivery to intestinal areas with abundant LF receptors.     

Incorporation of calcium salts into xanthan gum matrices: hydration,erosion and drug release characteristics

Xanthan gum (XG), a hydrophilic biopolymer with modified release properties, was used to produce directly compressed matrix tablets containing a model drug, sodium p-aminosalicylate. Three formulations were prepared, each containing a different calcium dihydrate salt: calcium chloride, calcium sulfate or dibasic calcium phosphate. The aim of the investigation was to relate the calcium ion content and solubility of the calcium salt to the in vitro drug release profile of the xanthan matrices. Tablet hydration, erosion and drug release were determined in distilled water using the British Pharmacopoeia (BP) paddle method. The data showed that the overall drug release was the greatest with addition of calcium sulfate, followed by calcium chloride and dibasic calcium phosphate. The chloride salt formulation displayed the greatest percentage erosion due to rapid mass loss during the initial phase, followed by those with sulfate or phosphate salts. As xanthan gel viscosity increased and drug release was also found to be lower, it can be concluded that drug release is influenced by the solubility of the salt present in the formulation, since these parameters determine the viscosity and structure of the gel layer.     

Hydration,Erosion, and Release Behavior of Guar-Based Hydrophilic Matrix Tablets Containing Total Alkaloids of Sophora alopecuroides

It is a challenge to deliver water-soluble drug based on hydrophilic matrix to colon because of swelling and erosion of polysaccharides in contact with media. In our study, guar-based hydrophilic matrix tablets containing water-soluble total alkaloids of Sophora alopecuroides prepared by wet granulation technique were evaluated. A novel method was established to investigate the changes of swelling and volume for guar-based tablets in undynamic state, which generally showed a rapid swelling and volume change in the first 9 h, then the hydrated speed slowed down. On the other hand, the influence of different pH of the media on water uptake and erosion of various guar-based formulations in dynamic state indicated that the hydrated constants in simulated gastric fluid (SGF) was higher than that in SIF, which followed varied mechanism of water penetration by fitting Davidson and Peppas model. The extent of erosion was between 22.4 and 32.6% in SIF within 360 min. In vitro sophoridine release studies in successive different mimicking media showed that the guar matrix tablets released 13.5–25.6% of sophoridine in the first 6 h; therefore it was necessary to develop the bilayer matrix tablet by direct-compressing coating 100 mg guar granula on core tablet. The initial release of coated tablet was retarded and the bilayer matrix tablet was suitable for colon target.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Preparation and characterization of chitosan microspheres containing doxifluridine

Chitosan microspheres containing 5-fluorouracil (5-FU), tegafur (FT), and doxifluridine (DFUR) were prepared by the dry-in-oil method using silicone oil with no surfactant as a dispersion medium. For DFUR-containing chitosan microspheres (DFUR-M), reacetylation with acetic anhydride or coating using chitosan and glutaraldehyde was performed. DFUR-M, reacetylated DFUR-M, and chitosan-coated DFUR-M were investigated on in vitro drug release, and the former two microspheres were examined for in vivo degradation after subcutaneous (s.c.) implantation in mice, and in vivo plasma concentration-time profiles after s.c. implantation in rats. The present method gave fairly large microspheres purely composed of chitosan and drug because of no use of surfactant, which showed the mean particle diameters of 300-900 µm and the drug contents of 4-22% (w/w). Encapsulation efficiency of DFUR was higher than that of 5-FU and FT. DFUR-M and reacetylated DFUR-M exhibited spherical shape except chitosan-coated DFUR-M. DFUR-M showed high initial rapid release, which was suppressed to some extent by reacetylation or chitosan coating. DFUR-M and reacetylated DFUR-M subcutaneously implanted were gradually degraded, and approximately half or a little more of the microspheres disappeared from the implanted site at 3 weeks postimplantation. DFUR-M and reacetylated DFUR-M implanted subcutaneously gave similar plasma concentration-time profiles of DFUR, which did not indicate prolonged release in vivo. DFUR-containing chitosan microspheres with fairly large size and good drug content could be obtained by the present preparation but remained to be improved for drug release properties.     

Matrix cracking and delamination in laminated composites. Part II: Evolution of crack density and delamination

This paper presents a model to predict the propagation of transverse cracks in polymer matrix composite laminates. Different possibilities for the crack pattern are analyzed and the different stress-strain response are compared. Taking into account that matrix cracking promotes delamination between the plies, the propagation of delamination is also simulated. The model predictions are compared with experimental data obtained in composite laminates that accumulate transverse cracks and delaminations before failing catastrophically. The possibility and limitations of a general constitutive law applied at ply level, as a mesomodel, is analyzed and the bounds of applicability of the model are explained.     

壳聚糖水凝胶的制备及其在药物释放中的应用

水凝胶作为性能良好的载体,在药物的控释、组织工程等领域有着广泛的应用。壳聚糖是一类天然的带正电荷的碱性多糖,由其形成的水凝胶具有较好的生物相容性、生物降解性、抗菌和低细胞毒性,因此,壳聚糖水凝胶有着良好的生物应用前景。本文综述了壳聚糖水凝胶的制备方法(包括物理交联法和化学交联法),在物理交联法部分着重介绍了离子化合物及聚电解质分子与壳聚糖通过离子交联形成水凝胶,以及利用分子链间的疏水作用形成壳聚糖水凝胶的方法;而在化学交联法部分介绍了合成壳聚糖水凝胶的化学手段,包括交联剂、光照辐射和酶的使用。继而概述了壳聚糖水凝胶在药物缓释应用方面的研究进展,包括温度、pH值和电场响应的药物控释体系。最后展望了壳聚糖水凝胶未来的发展前景。     

Investigation of Hypromellose Particle Size Effects on Drug Release from Sustained Release Hydrophilic Matrix Tablets

Selected combinations of six model drugs and four hypromellose (USP 2208) viscosity grades were studied utilizing direct compression and in vitro dissolution testing. Experimental HPMC samples with differing particle size distributions (coarse, fine, narrow, bimodal) were generated by sieving. For some formulations, the impact of HPMC particle size changes was characterized by faster drug release and an apparent shift in drug release mechanism when less than 50% of the HPMC passed through a 230 mesh (63 μm) screen. Within the ranges studied, drug release from other formulations appeared to be unaffected by HPMC particle size changes.     

Channeling Agent and Drug Release from a Central Core Matrix Tablet

A new oral dosage form for controlled and complete release of drug after a predetermined lag time is described. The system, designed to exploit the relatively constant small intestine transit time, consists of a drug-containing core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol, and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be dependent on type and particle size of the channeling substances used. Also, rheological properties of the binary mixtures (channeling substance-polymer) can affect the lag time periods. On the other hand, the release kinetics were found to be influenced significantly by excipient type and particle size. Results obtained from in vitro dissolution testing demonstrated that this device potentially could be used to deliver drugs orally for up to once-a-day dosing at controllable rates.     

Channeling Agent and Drug Release from a Central Core Matrix Tablet

A new oral dosage form for controlled and complete release of drug after a predetermined lag time is described. The system, designed to exploit the relatively constant small intestine transit time, consists of a drug-containing core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol, and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be dependent on type and particle size of the channeling substances used. Also, rheological properties of the binary mixtures (channeling substance–polymer) can affect the lag time periods. On the other hand, the release kinetics were found to be influenced significantly by excipient type and particle size. Results obtained from in vitro dissolution testing demonstrated that this device potentially could be used to deliver drugs orally for up to once-a-day dosing at controllable rates.     

Matrix cracking and delamination in laminated composites. Part I: Ply constitutive law, first ply failure and onset of delamination

Matrix cracking and delamination are the main initial forms of damage in advanced laminated composites manufactured by stacking unidirectional plies of fiber reinforced polymers. In this paper, the onset of matrix cracking is determined for in-plane stress states; in addition, delamination promoted by matrix cracks is analyzed. Taking into account that under in-plane shear stresses composite laminates show a non-linear response prior to the formation of a macro-crack, a plastic-damage model is proposed and implemented. The models predictions correlate well with published experimental data.