Properties of calcium-induced gel beads prepared with alginate and hydrolysates

Calcium-induced alginate gel beads (Alg-Ca) containing alginate hydrolysate, such as the guluronic acid block (GB), was prepared and the drug release profiles were investigated under simulated gastrointestinal conditions. The addition of GB to Alg-Ca altered its rheological properties. A model drug (hydrocortisone) was incorporated at 78% of its theoretical yield within the dried Alg-Ca containing 5% GB and it was gradually released from the beads in JP XIV 1st medium for disintegration test (pH 1.2), while it was rapidly released with disintegration of the gel matrix in JP XIV 2nd medium (pH 6.8). In contrast, for Alg-Ca containing GB and chitosan, disintegration was not observed in these media and the drug release rate was markedly different. These results demonstrate that the release profiles of drugs incorporated into Alg-Ca can be controlled by adding these polysaccharides.     

The drug release profile from calcium-induced alginate gel beads coated with an alginate hydrolysate

Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate (Alg), e.g. the guluronic acid block (GB) was prepared and the model drug, hydrocortisone release profiles were investigated under simulated gastrointestinal conditions. Their molecular weights were one sixth or one tenth that of Alg and the diffraction patterns of the hydrolysates resembled that of Alg. The drug release rate from Alg-Ca coated with GB apparently lowered than that of Alg-Ca (coating-free) in the gastric juice (pH1.2). And the coating did not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8) and the gel erosion accelerated the drug release. On the other hand, for the coated Alg-Ca containing chitosan, the drug release showed zero-order kinetics without rapid erosion of Alg-Ca. The drug release rate from Alg-Ca was able to be controlled by the coating and modifying the composition of the gel matrix.     

Adsorption of bile acid by chitosan-orotic acid salt and its application as an oral preparation

The orotic acid (OT) salt of chitosan (CS), CS-OT, and that of a CS derivative, CP, were prepared, and the adsorption of primary or secondary bile acid was investigated. Calcium-induced alginate gel beads (Alg-Ca) containing CS-OT were also prepared and autoclaved, and the possibility of these beads to act as a vehicle for oral administration to prevent hyperlipidemia was investigated. When taurocholate (TCA) and glycocholate (GCA) were present together in the medium, CS-OT adsorbed identical amounts of both bile acids. This trend was seen in all CPs, although the capacity to adsorb bile acid was affected by the number and/or structure of the amino groups in the CP. On the other hand, taurodeoxycholate, a secondary bile acid was preferentially adsorbed over TCA and GCA. Alg-Ca containing CS-OT took up bile acids in a similar manner as CS-OT irrespective of the water content of the gel matrix. As all elements can be taken as a food, Alg-Ca containing CS-OT could serve as a useful dietary agent for the prevention of hyperlipidemia, which is a lifestyle-related disease.     

pH-dependent release from ethylcellulose microparticles containing alginate and calcium carbonate

Ethylcellulose microparticles containing alginate and calcium carbonate nanoparticles were prepared by spray drying water-in-oil emulsion. Alginate solution (3%) in distilled water was used as an aqueous phase, ethylcellulose solution (5%) in dichloromethane as an oil phase, and sorbitan sesquioleate as an emulsifier. The nanoparticles of calcium carbonate were dispersed into the emulsion. By spray-drying the emulsion, ethylcellulose microparticles containing alginate and calcium carbonate were obtained. When the ratios of alginate to calcium carbonate were 4:1 and 2:1, the pH dependency of the release was marked and the degree of release was suppressed in acidic conditions. When the ratio increased to 1:2, the degree of release increased while the pH-dependent release profiles were maintained. Cavities created by the dissolution of calcium carbonate could account for the increased release.     

Dynamic Release of Propranolol HCl from Cationic Ion–Exchanger–Loaded Calcium Alginate Beads

The dynamic release of drug propranolol HCl from the propranolol HCl–resin complex (PRC) loaded calcium alginate beads has been studied in the buffer media of pH 1.2 at the physiological temperature 37°C. The PRC encapsulated beads demonstrated nearly 58.04% release while naked PRC particles released 98.00% drug in 24 h in the gastric fluid. The amount of drug released was found to increase with and decrease in the amount of sodium alginate in the beads. Similarly, with the increase in the amount of entrapped PRC particles within the beads, the quantity of drug released was also observed to increase. The degree of crosslinking of beads also affected the release kinetics. Interestingly, the release from naked PRC particles followed ‘first‐order’ kinetics while PRC particles, entrapped in calcium–alginate beads, exhibited ‘diffusion controlled’ release behavior as indicated by liner nature of fractional release vs. √t plot.     

Characterization of dual layered pellets for sustained release of poorly water-soluble drug

The aim of this study was to develop pellet formulations that could be used to improve the dissolution and bioavailability of a poorly water-soluble model drug, cisapride. Six different types of pellets were prepared by coating sugar spheres in a fluidized bed coater. When the sugar spheres were single layered containing cisapride and solubilizer such as polysorbate 80, the resulting pellets provided an instant release of cisapride in the simulated gastric fluid. Dissolution tests carried out in the simulated intestinal fluid showed that there were negligible amounts of cisapride released, regardless of the pellet formulation. To succeed in attaining dissolution and the sustained release of cisapride at a neural pH, the single layered pellets were coated again with a coating suspension containing Eudragit RS 30D and L 30D. Scanning electron microscopy revealed that the dual layered pellets had a crack-free and spherical surface. Interestingly, the dual layered pellets provided the sustained release of cisapride in both the simulated gastric and intestinal fluids. The composition and components of the dual layers were found to be key parameters affecting the pattern of cisapride dissolution. Significant improvement in the bioavailability of cisapride was achieved when the dual layered pellets were administered orally to dogs. Overall, these results suggest that the dual layered pellets have potential as a sustained release dosage form for poorly water-soluble drugs.     

Microencapsulation of DNA Within alginate microspheres and crosslinked chitosan membranes for in vivo application

Calf thymus DNA was microencapsulated within crosslinked chitosan membranes, or immobilized within chitosan-coated alginate microspheres. Microcapsules were prepared by interfacial polymerization of chitosan, and alginate microspheres formed by emulsification/ internal gelation. Diameters ranged from 20 to 500 Μm, depending on the formulation conditions. Encapsulated DNA was quantifiedin situ by direct spectrophotometry (260 nm) and ethidium bromide fluorimetry, and compared to DNA measurements on the fractions following disruption and dissolution of the microspheres. Approximately 84% of the DNA was released upon core dissolution and membrane disruption, with 12% membrane bound. The yield of encapsulation was 96%. Leakage of DNA from intact microspheres/capsules was not observed. DNA microcapsules and microspheres were recovered intact from rat feces following gavage and gastrointestinal transit. Higher recoveries (60%) and reduced shrinkage during transit were obtained with the alginate microspheres. DNA was recovered and purified from the microcapsules and microspheres by chromatography and differential precipitation with ethanol. This is the first report of microcapsules or microspheres containing biologically active material (DNA) being passed through the gastrointestinal tract, with the potential for substantial recovery.     

Pickering emulsions stabilized by hydrophobically modified alginate nanoparticles: Preparation and pH-responsive performance in vitro

pH-responsive Pickering emulsions were prepared, taking the hydrophobic modified calcium alginate nanoparticles (MCA) of pH sensitivity as emulsifiers. The MCAs were obtained via gelation between Ca²⁺ in emulsion and alginate sodium that reacted with diacetone acrylamide since alginate sodium was too hydrophilic to be used as a stabilizer. The effect of MCA characteristics, Ca²⁺ content, and pH on the preparation and property of emulsion was evaluated. Then, the released behaviors of MCA-stabilized emulsion loading oil-soluble drug of curcumin were investigated in vitro. The results demonstrated that Pickering emulsions released curcumin intestine-specifically (37% in 4 hours with a pH of 6.8), compared with the one in the gastric fluid (3% in 4 hours with a pH of 1.5), proving that MCA had similar pH sensitivity to alginates and probably as the promising candidate in oral drug controllable release.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

萘普生在介孔分子筛MCM-41中的负载及其溶出性能

用含氨基的偶联剂修饰介孔分子筛MCM-41的表面,将修饰前和修饰后的介孔分子筛分别负载难溶性药物萘普生（NAP）,利用X射线衍射、傅里叶变换红外光谱、差示扫描量热分析、扫描电子显微镜、透射电子显微镜和N2吸附 脱附分析等技术分别对其进行了结构表征和性能测试。 结果表明,药物分子存在于分子筛的孔道中。 负载在MCM-41中的萘普生溶出速率远优于原料药,60 min时大约溶出70%。 氨基修饰后的药物释放速率比修饰前有所减慢,表明可通过氨基修饰调节释放速率。     

Bone cell activity responsive drug release from biodegradable apatite/collagen nano-composite cements--in vitro dissolution medium responsive vitamin K2 release

A biodegradable drug delivery system with perforated macro pores was established using an apatite/collagen composite cement containing menatetrenone (VK2). The drug-release capabilities of the device were investigated in vitro under osteoblast and osteoclast-like conditions (SOB and SOC). A bulk powder of apatite cement containing 2.5% VK2 and 20% bovine collagen was obtained by grinding, kneaded with phosphoric acid, and poured into molds, producing fixed blocks with 0-60 perforated macro pores. The characteristics of these samples were measured by X-ray powder diffraction analysis and Fourier-transformed and infrared spectroscopy, and found to be very similar to those of natural bone. Drug release tests were performed under SOB in simulated body fluid (pH 7.8), and then under SOC in acetate buffer (pH 4.5) at 37.0±0.1 °C, and the process repeated twice. The device released almost no drug in SOB, but a significant amount in SOC. The drug release in SOC was not proportional to the number of macro pores in the first test, but was in the second. The device showed dissolution medium-responsive drug release.     

Bipolymeric Pectin Millibeads Doped with Functional Polymers as Matrices for the Controlled and Targeted Release of Mesalazine

Targeted drug delivery systems are a very convenient method of treating inflammatory bowel disease. The properties of pectin make this biopolymer a suitable drug carrier. These properties allow pectin to overcome the diverse environment of the digestive tract and deliver the drug to the large intestine. This investigation proposed bipolymeric formulations consisting of the natural polymer pectin and a synthetic polymer containing the drug 5-aminosalicylic acid. Pectin beads were prepared via ionotropic gelation involving the interaction between the hydrophilic gel and calcium ions. The obtained formulations consisted of natural polymer, 5-aminosalicylic acid (5-ASA) and one of the synthetic polymers, such as polyacrylic acid, polyvinylpyrrolidone, polyethylene glycol or aristoflex. The release of the drug was carried out employing a basket apparatus (USP 1). The acceptor fluid was pH = 7.4 buffer with added enzyme pectinase to reflect the colon environment. The amount of the released drug was determined using UV-Vis spectrophotometry at a wavelength of λ = 330 nm. The kinetics of the drug dissolution revealed that none of the employed models was appropriate to describe the release process. A kinetic analysis of the release profile during two release stages was carried out. The fastest drug release occurred during the first stage from a formulation containing pectin and polyethylene glycol. However, according to the applied kinetic models, the dissolution of 5-ASA was rather high in the formulation without the synthetic polymer during the second stage. Depending on the formulation, 68–77% of 5-ASA was released in an 8-hour time period. The FTIR and DSC results showed that there was no interaction between the drug and the polymers, but interactions between pectin and synthetic polymers were found.     

Side effect reduction of encapsulated hydrocortisone crystals by insulin/alginate shells

Insulin/alginate (ALG) microcapsules for controllable release and side effect reduction of a glucocorticoid have been fabricated via the layer-by-layer (LbL) assembly technique. Insulin and ALG are deposited alternately onto hydrocortisone (HC) crystals to form a core-shell structure. This insulin/ALG microcapsule can prolong the release of HC under physical conditions and control the HC release rate by adjusting the number of insulin/ALG bilayers adsorbed onto HC crystals. The release of insulin from the capsule wall exhibits a little lag, compared with that of the HC. It is a great advantage for this system because hyperglycemia caused by HC usually arises a few hours after its administration, which could be inhibited by the delayed release of insulin from the shell of the microcapsule. This synergy effect might enable a new way of using one carrier to deliver two kinds of drugs and reduce their side effects at the same time.     

Monoolein cubic phase including in situ ionically gelled alginate and its salt-responsive release property

Salt-responsive monoolein (MO) cubic phase was prepared by in situ ionically gelling alginate contained in its water channels. On the TEM micrographs, bilayers, and water channels, characteristic of MO cubic phase were observed, and alginate and CaCl₂ had little effect on the structure. According to the differential scanning calorimetric thermogram, the cubic-to-hexagonal phase transition temperature of the cubic phase containing CaCl₂ solution was 46.8°C and it was much lower than that of the cubic phase containing distilled water, 60.5°C. The transition temperature was not significantly affected by alginate. The phase transition temperatures measured by the calorimetric analysis were in accordance with those determined by polarized optical microscopy. An initial burst release of dye (i.e., amaranth) was observed when the gelled alginate was not contained in the water channel of the cubic phase. A sustained release was obtained with the cubic phase containing the gelled alginate. The release of dye loaded in the cubic phase containing the gelled alginate was significantly promoted when the cubic phase came into contact with PBS (10?mM, pH 7.4), possibly because the multivalent cation (Ca²⁺) bound to alginate chains could be replaced by the monovalent cation (Na⁺).     

Monoolein cubic phase containing alginate/cystamine gel for controlled release of epidermal growth factor

Monoolein (MO) cubic phase including alginate and cystamine in its water channel controlled the release of epidermal growth factor (EGF) by responding to changes in pH value and the reductive conditions of the release medium. The crosslinking degree of alginate gel with cystamine and the complex coacervation of alginate and EGF were investigated by using light scattering. TEM micrographs of cubic phases revealed MO bilayers along with water channels. Differential scanning calorimetry indicated that the cubic-to-hexagonal phase transition took place at 60.2?°C. Additives such as stearyl trimethyl ammonium chloride and cystamine decreased the transition temperature by a few to more than 10?°C. The release of EGF loaded in cubic phases was completed in 5?h and, thereafter, no significant additional release was observed. The release % of EGF loaded in MO cubic phase containing alginate and cystamine increased not only with the increase of pH but also glutathione concentration. The MO cubic phase containing alginate/cystamine gel can be used as a carrier for the delivery of peptide and protein drugs.     

Gelatin scaffolds functionalized by silver nanoparticle‐containing calcium alginate beads for wound care applications

The embedding of silver nanoparticle (nAg)‐containing calcium alginate (CaAlg) beads in gelatin scaffolds was aimed to reduce the burst release and prolong the release of silver (Ag⁺) ions for a long period of time. The reduced sizes of the nAg‐containing CaAlg beads were prepared by an emulsification/external gelation method. The diameter of these beads was ~2 µm. The nAg‐containing CaAlg beads were then embedded into gelatin scaffolds by a freeze‐drying method for evaluating the potential of these scaffolds as wound dressings. The compressive modulus of these scaffolds embedded with nAg‐containing CaAlg beads ranged between 7 and 9 kPa. For release study, the cumulative released amounts of Ag⁺ ions from the nAg‐containing CaAlg beads embedded in gelatin scaffolds were lower than those from the nAg‐containing CaAlg beads. Moreover, the nAg‐containing CaAlg beads embedded in gelatin scaffolds had great antibacterial activity and low cytotoxicity. Thus, these scaffolds had potential for sustaining the release and use in wound care applications, especially chronic wound. Copyright © 2016 John Wiley & Sons, Ltd.     

Fabrication,characterization, and drug release study of vitamin C–loaded alginate/polyethylene oxide nanofibers for the treatment of a skin disorder

Pigmented purpuric dermatosis (PPD) is a skin disorder mainly seen in the lower limbs. The nanofibrous web has been shown to be an appropriate alternative for the treatment of skin diseases as a drug delivery vehicle. In this study, sodium alginate (SA)/polyethylene oxide (PEO) nanofibers containing vitamin C (VC) were fabricated using both blended electrospinning and core/shell electrospinning. The resultant nanofibers were characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. Enhancing the VC content resulted in increasing the nanofibers diameter. Also, the degradation rate and drug release were investigated. Drug release was evaluated using the in vitro dissolution and permeation method. The degradation rate and the drug release of the core/shell nanofibers were found to be lower than those of the blended nanofibers. The drug release of the extended nanofibers followed a different pattern, indicating that the extension of the nanofibers could be a promising way to control the drug release.     

The effect of sodium alginate on physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer

The aim of this study was to investigate the effect of sodium alginate on the physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The mean values of the shape factor (e(R)) and the aspect ratio of Surelease-matrix pellets were 0.615-0.625 and 1.06-1.070, respectively, indicating good sphericity of the pellets. The drug release rate increased as the amount of sodium alginate increased due to hydration, swelling, and erosion within the Surelease-matrix pellets. In addition, the porosity of pellets also increased with increasing sodium alginate content. The results of this study show that sodium alginate has a greater effect on the drug release rate than the drug release mechanism within the Surelease-matrix for sparingly water-soluble drug, such as tamsulosin hydrochloride.     

Dynamic Release of Riboflavin from Ethyl Cellulose Coated Barium Alginate Beads for Gastrointestinal Drug Delivery: An in vitro Study

The present work describes the dynamic release of model drug riboflavin form uncoated and ethyl cellulose coated barium alginate beads in the media of continuous varying pH at the physiological temperature 37°C. The drug release behavior has been studied in the simulating gastric fluid (SGF, pH 1.2) for 0–2 h and then in the simulating intestinal fluid (SIF pH 6.8) for 2–48 h. In addition to the traditional dissolution test (TDT, the dynamic release has also been studied by a newly developed method, called ‘flow through diffusion cell’ (FTDC). The release profiles, obtained by using these two methods have been found to differ appreciably from each other. Moreover, the nature of the solid mass surrounding the beads in the FTDC method also influences the release behavior of beads. The uncoated beads demonstrated faster drug release of drug in the medium of lower pH (i.e., 1.2) as compared to that in the medium of pH 6.8 and the release process was found to be diffusion controlled.     

Effect of the Addition of Alginate and/or Tetracycline on Brushite Cement Properties

Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.