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.     

Preparation of hydroxyapatite-calcium ferrite composite for application in loading and sustainable release of amoxicillin: Optimization and modeling of the process by response surface methodology and artificial neural network

In this research, a merit carrier consisting of hydroxyapatite and calcium ferrite (HAp-CaFe₂O₄) was prepared via a convenient procedure and characterized using a series of techniques, including XRD, FE-SEM, TEM, EDS mapping, BET/BJH, VSM, and TGA. The loading of Amoxicillin (AMX) onto HAp-CaFe₂O₄ was optimized and modeled by two powerful approaches, namely response surface methodology (RSM) and artificial neural network (ANN). RSM-optimized results demonstrated that the maximum drug loading efficiency was 91.76% at a carrier dosage of 1.2 g, a drug concentration of 30 mg L^?1, and a pH of 6.5 within a stipulated time of 60 min. ANN modeling revealed that the pH of the solution had a dramatic effect with a 35% impact on the drug loading process. The downloading of AMX by HAp-CaFe₂O₄ was consistent with pseudo-2nd order and intra-particle diffusion kinetics models as well as the Temkin isotherm model, implying the chemisorption of the drug molecules on the carrier. The AMX release was evaluated at different pHs, and it was revealed that the sustained and prolonged drug evacuation occurred in the neutral medium as compared to acidic and basic media. The conformity of the drug release kinetics to the Korsmeyer-Peppas model indicated that the Fickian diffusion dominated the AMX release. The MTT assay showed the biocompatibility and safety of HAp-CaFe₂O₄ toward A549 cell lines.In summary, as-prepared HAp-CaFe₂O₄ can be regarded as a biocompatible and stimuli-responsive carrier for controlled and targeted drug delivery systems.     

Effect of pore geometry on the sintering of Ca-based sorbents during calcination at high temperatures

In this article, we present a mathematical model that describes the calcination and sintering of calcium-based sorbents in furnace sorbent injection (FSI) conditions. We assumed that the sorbent decomposition follows a shrinking core model with a changing pore size distribution in every layer and we used a comprehensive mathematical model for sintering. Cylindrical and plate-like or slit pore geometries, usually associated with carbonate- and hydroxide-derived sorbents, respectively, were adopted and compared. It was concluded that sorbents with cylindrical pores sinter to a greater extent than those with slit pores. The decomposition and sintering kinetics were determined for three calcium sorbents with different pore geometries in FSI conditions. The study revealed that the presence of CO₂ and H₂O in the reaction atmosphere affects the sintering parameters whereas the calcination parameters remain constant. The model effectively correlated the experimental data and adequately predicted not only the evolution of the specific surface area but also the evolution of the pore size distribution of the sorbent over time. The most striking aspect of the research was that although our model calculated the total area by adding together the pore sizes in all the layers of the sorbent, the results were very similar to those of other sintering models.     

Hierarchical self-assembled hollow hydroxyapatite flower microspheres containing terpene functional groups for efficient drug loading and pH-responsive drug release

In this paper, we fabricated hierarchical self-assembled hollow rose-like flower microspheres (HRFM) and hollow burr-like flower microspheres (HBFM) hydroxyapatite (HAP) using dehydroabietyl phosphate tri-ester (DDPT) as an organic phosphorus source, a regulating agent, and a soft template simultaneously via a one-step solvothermal method. The HBFM and HRFM have been explored for their application in drug delivery, using doxorubicin (DOX) as a drug model. The formation mechanisms of HRFM and HBFM were proposed on the basis of the electrostatic potential diagrams and self-assembled behavior of DDPT organic molecule. After the rosin-based terpene functional groups were incorporated, both HRFM and HBFM exhibited low cytotoxicity against Hela cell, pH-dependent sustained drug release properties, and high drug loading capacity. The drug-loading capacities of HBFM and HRFM were 116.6?mg?g^?1 and 148.3?mg?g^?1, respectively. Thus, the as-prepared HRFM and HBFM are promising for the applications in drug delivery.     

Influence of ionic substitution in improving the biological property of carbon nanotubes reinforced hydroxyapatite composite coating on titanium for orthopedic applications

The present work is aimed for the development of carbon nanotubes (CNTs) reinforced single mineral (Sr, Mg, Zn) as well as multi minerals (Sr+Mg+Zn) substituted hydroxyapatite composite (M-HAP) coatings on titanium (Ti). The effect of different mineral ions substitution and CNTs reinforcement in HAP composite coating is discussed in detail. Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX), and high resolution transmission electron microscopy (HRTEM) were used to characterize the structural and morphological behavior of the composite coatings. The corrosion resistance of the composite coatings in simulated body fluid (SBF) solution was evaluated by the potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) studies. In addition, the biocompatibility of the composite coatings was evaluated by in vitro culture of human osteoblast MG63 cells on the composite coated Ti. All these results essentially suggest that CNTs/M-HAP composite coated Ti can be a potential candidate for orthopedic applications.     

Influence of deposition temperature on the properties of hydroxyapatite obtained by electrochemical assisted deposition

Surface functionalization of pure titanium (cp-Ti) with hydroxyapatite (HAp) was successfully achieved by means of electrochemical deposition (ED) in a solution containing calcium nitrate and ammonium dihydrogen phosphate. The aim of this study is to evaluate the influence of the deposition temperature on the elemental and phase composition, chemical bonds, morphology, and in vitro electrochemical behaviour in biological simulated media (simulated body fluid - SBF). The roughness and wettability of the developed coatings are also investigated. By increasing the deposition temperature from 50 °C to 75 °C, the HAp coatings present a well-crystalized structure, denser and a nobler behaviour in terms of electrochemical behaviour in SBF at 37 °C. Also, by increasing the deposition temperature from 50 °C to 75 °C, the contact angle has decreased from 76.1° to 27.4°, exhibiting a highly hydrophilic surface. Taking into consideration all the obtained data, electrodeposition of HAp at 75 °C was found preferable when compared to 50 °C. The characteristics of the HAp coatings can be easily adjusted by optimizing the electrochemical deposition parameters and/or controlling specific features like pH, temperature, or ionic concentration of electrolyte, etc.     

Osseointegration of sputtered SiC-added hydroxyapatite for orthopaedic applications

Over the last few years, a trend in medical applications is to find solutions for metallic implants using coatings that can improve bioactivity and osseointegration. The goal of this study was to obtain and investigate sputtered hydroxyapatite coatings enriched with SiC to enhance the bioactivity and osseointegration of Ti alloys used in orthopaedic applications. The films were characterized in terms of phase composition, roughness, corrosion resistance in a synthetic body fluid (SBF) and in vitro biocompatibility with MG 63 osteoblast-like cells. All of the investigations were conducted using XRD, AFM, cell viability assays and proliferation tests. The results revealed that the addition of SiC had a positive influence on the properties of the sputtered hydroxyapatite. The addition of SiC led to an improvement in coating adhesion and corrosion resistance in an SBF solution over the HAP coating. All of the coatings presented cell viability values over 90%, revealing their suitability for medical applications.     

Influence of concentration of hydroxyapatite surface modifier agent on bioactive composite characteristics

The characterization of chitosan – hydroxyapatite (CH – HAp) composite sponges prepared via freeze-drying methodology is reported in this study. Stearic acid (SA), added as a surface modifier of the HAp nanoparticles, induced changes in the TG/DTG results, particle size distribution and particle morphology. Composite sponges prepared with SA coated HAp demonstrated enhanced biocompatibility and structural properties, as compared to the composites prepared with uncoated HAp. SA coating modified the morphology of the composite, promoting a better dispersion of HAp particles within the composite sponges, and better homogeneity of the polymeric cover with HAp particles. The viability of the composites for cell culture applications was analyzed, and the results suggest that the sponges are biocompatible. Therefore, SA proved to be a good candidate for surface coating of HAp nanoparticles prevent agglomerations, and could be used effectively in the preparation of biocompatible composite sponges with chitosan.     

Appraisal of a cementitious material for waste disposal: Neutron imaging studies of pore structure and sorptivity

Cementitious materials are conventionally used in conditioning intermediate and low level radioactive waste. In this study a candidate cement-based wasteform has been investigated using neutron imaging to characterise the wasteform for disposal in a repository for radioactive materials. Imaging showed both the pore size distribution and the extent of the cracking that had occurred in the samples. The rate of the water penetration measured both by conventional sorptivity measurements and neutron imaging was greater than in pastes made from Ordinary Portland Cement. The ability of the cracks to distribute the water through the sample in a very short time was also evident.The study highlights the significant potential of neutron imaging in the investigation of cementitious materials. The technique has the advantage of visualising and measuring, non-destructively, material distribution within macroscopic samples and is particularly useful in defining movement of water through the cementitious materials.     

Relations between apparent and intrinsic kinetics of “programmable” drug release in human plasma

To better understand and “program” the drug release in human plasma, a kinetic characterization of the process is necessary for every drug ligand and macromolecular support. Due to few observed species and limited standard information, process modelling based on extended kinetic structures is difficult. Laboratory experiments that mimic the natural conditions and the bio-environment, together with statistical estimators allow identification of reduced (apparent) kinetic models. The scope of this paper is to present a more systematic approach to interpret the kinetic models and to link the identified apparent rate/equilibrium constants to kinetic characteristics of an extended “intrinsic” reaction path. The developed stoichiometric analysis and linear lumping rules are exemplified for a case study from literature, that considers a four-ligands (“drug” dansyl groups) release from a dendrimeric support structure in a reducing environment that mimic the human plasma.     

几种缓释尿基复合肥氮素释放的动力学研究

采用 2种恒温 (2 5℃ ,37℃ )培养试验研究了 4种化学物质 (B1 、B2 、HQ和 DCD)对尿素氮释放的缓效作用和用该化学物质研制 5种缓释尿基复合肥氮释放的动力学效应及其对土壤无机氮的影响。结果表明 ,中、高浓度B1 、B2 对土壤脲酶的抑制作用优于 HQ ,可作为高效无残毒的理想脲酶抑制剂 ;2 5℃下培养 14天 ,3种化学物质 (B1 、B2 、HQ)均明显降低尿素中氮的释放总量、释放速率和平均释放速率。施用缓释尿基复合肥对土壤无机氮含量的影响大 ,含 DCD的缓释复合肥 NH4 + N释放总量高 ,而 NO3- N数量低 ;含硼的 3种缓释尿基复合肥铵释放的动力学与环境温度关系密切 ,在 37℃下 ,铵释放速率大且峰值出现时间早 ;2 5℃时铵释放速率高峰期大大延迟 ,释放绝对量低 ;两种温度下表征铵释放的数学方程 y=a+blogt和 y=a+bt1 /2的 b值 (铵释放速率常数 )可作为衡量 5种缓释尿基复合肥养分释放性能的指标。缓释尿基复合肥对土壤无机氮释放过程的动力学效应能用一级反应动力学方程 Nt=No(1- ekt)极好地描述 ,在 4 2天内 ,土壤 NH4 + N和无机氮释放潜力 (No值 )均以 4种含硼缓释复合肥为低 ,仅为CK的 5 3.5 %～ 6 3.8%     

The effect of chemical composition and morphology on the drug delivery properties of hydroxyapatite-based biomaterials

In the case of orthopedic and dental interventions, local antibiotic therapy reduces significantly the risk associated with the intervention. The aim of this study was the preparation and characterization of pure hydroxyapatite (HA), Si- and Mg-doped HA, which ensures the sustained release of doxycycline, and the investigation of the parameters, which were crucial for the drug release. The carriers were synthesized using the precipitation method. In order to achieve different morphologies, traditional drying and spray drying methods were used: Si-doped HA was prepared using two different sources of Si, Na₂SiO₃ and Ludox AS-40, while (Mg(NO₃)₂)*6H₂O was used for substitution with Mg. The carriers were characterized by XRD, SEM, EDX and TG/DTA methods, and the ion incorporation was also confirmed by lattice parameters calculations. Doxy was bound on the carriers by physical adsorption, the adsorption capacity increased proportionally by increasing the concentration of the initial Doxy solutions (10, 15, 20, 25 g/L). The investigated systems showed different releases with the change of the dissolution medium (in the case of HA microspheres, the release in PBS was twice as high as in SBF), chemical composition and morphology of the carriers. The retard effect of the carriers was improved by the spherical morphology, and the reduced release by ion substitution in both SBF and PBS increased as follows: HA < HASi1<HAMg < HASi2. The release mechanism of Doxy was discussed through five different release kinetics models.     

Comparative study of the hydroxyapatite coatings prepared with/without substrate bias

The aim of this paper is to prepare the hydroxyapatite by Ion Beam Assisted Deposition and to investigate in terms of its elemental and phase composition, roughness and in vitro corrosion resistance. The coatings were prepared with and without applying bias on substrate, in order to find the effect of bias on the chemical, structural, morphological and anti-corrosive properties. The biased coatings exhibited Ca/P ratio closer to the value of the stoichiometric HAP (1.67). The phase composition is not affected by the bias evolution. The adhesion of both coatings is still satisfactory for biomedical applications, irrespective of the bias. Hydroxyapatite deposited without bias presented the best corrosion resistance in SBF at 37 °C, probably due to its smooth surface and low porosity. Moreover, this coating proved to have the highest protection ability at the SBF corrosive attack.     

Preparation of hydroxyapatite coating on smooth implant surface by electrodeposition

A novel process for the deposition of a hydroxyapatite (HA) coating on a smooth implant surface has been developed. Specimens were firstly subjected to electrodeposition at −1.8 V (versus Ag/AgCl) in a mixed solution of 0.042 M Ca(NO₃)₂·4H₂O and 0.025 M NH₄H₂PO₄ at 85 °C for 5 s, and then post-treated in 1 M NaOH solution for 30 min. The experimental results showed the specimens prepared by the designed process to have better adhesion properties than those prepared by the traditional electrodeposition process.     

Hydrothermal synthesis of hierarchical hydroxyapatite: Preparation, growth mechanism and drug release property

Hydroxyapatite (HAP) hierarchical microspheres were synthesized by a facile hydrothermal method using calcium nitrate and ammonium dihydrogen phosphate through controlling complexing agents. The influences of two kinds of complexing agents (potassium sodium tartrate tetrahydrate and trisodium citrate) and reaction time on the morphology of HAP crystals have been investigated. These results indicate that complexing agents have a great influence on the morphology of HAP. When potassium sodium tartrate tetrahydrate was used as complexing agent, HAP flowers were composed of the network of nanosheet building blocks. Well-crystallized HAP dandelions with nanorods radiating from the center can be obtained by the introduction of trisodium citrate. Broader XRD diffraction peaks imply a nanometer scale size. Based on XRD and SEM results, the formation mechanism of HAP crystals has been discussed. The hierarchically structured HAP microspheres were explored as drug carriers. The results indicate that HAP flowers and dandelions showed a favorable sustained release property for ibuprofen; thus, they are very promising for application in drug delivery.     

Boron nitride nanoplatelets induced synergetic strengthening and toughening effects on splats and their boundaries of plasma sprayed hydroxyapatite coatings

Boron nitride nanoplatelets (BNNPs) with excellent mechanical properties were introduced into HA coatings fabricated through plasma spray in this research. SEM observation and Raman results revealed the added BNNPs retained their original structure even after harsh process and distributed homogeneously in the as-sprayed coatings. As compared with the monolithic HA coating, a 2.0?wt%BNNP/HA coating exhibited significant improvement (~ 40.3%) in fracture toughness and moderate enhancement (~ 20.0%) in indentation yield strength. Synergetic strengthening and toughening mechanisms which are operative through splat boundaries and individual splats were proposed. At splat boundaries, these embedded BNNPs induced stronger adhesion between the adjacent splats to resist splat sliding, which is evident from the fact that the calculated inter-splat friction force of an as-sprayed BNNP/HA coating was increased by ~7.3% at 2.0% BNNP weight fraction. Within splats, toughening mechanisms such as BNNP pullout, crack bridging by both anchored BNNPs and nanosized HA grains, crack deflection and crack propagation arrested by the embedded BNNPs were observed to improve toughness. Moreover, thermal mismatch between HA matrix and BNNPs during cooling process after plasma spray would induce the pre-existing dislocations formed around these BNNP nanofillers, which was assumed to hold out the effect of Orowan-type strengthening within splats.     

Influence of superplasticizers on the hydration of cement and the pore structure of hardened cement

This paper describes the influence of various types of superplasticizers such as naphthalene type (β-NS), refined lignin sulfonate type (LS) and polycarboxylate types (P34, S34) on the hydration of cement and the pore structure of hardened cement. Other superplasticizers except β-NS delayed the initial hydration of cement. In any case, it hardly influences the hydration reaction at late stage of cement. The retardation by the addition of superplasticizers is not observed after 28 days of curing. Large pores of 0.1 μm or more for hardened cement with LS or β-NS are larger than those of hardened samples with P34 or S34 cured for 28, 56 and 91 days. This is related to the coagulated structures of fresh cement pastes with various types of superplasticizers. It was presumed that the size of the cluster of aggregated particles became small when S34 or P34 that has a high dispersing ability was added compared to LS or β-NS that has a lower dispersing ability.     

Influence of magnesium and silver ions on rheological properties of hydroxyapatite/chitosan/calcium sulphate based bone cements

Rheology of bioceramic bone cements is usually described as properties of ceramic slurries, neglecting the self-setting character of these materials. In our studies calcium sulphate based bone cements with Ag⁺, Mg²⁺ and Mg²⁺/CO₃^2- modified hydroxyapatite were investigated. Despite of expectations, it has been proven that the presence of magnesium ions significantly influence the rheological properties of cement pastes. Changes in rheological properties were connected with (I) chemical interactions between Mg²⁺ and sulphate ions (II) chemical interaction between Mg²⁺ and chitosan. These effects were not observed for silver additive. Most of the developed calcium sulphate based pastes, except material containing MgHA and chitosan, have been categorized as thick pastes applicable with the spatula. It has been found that the chitosan present around and at the calcium sulphate grains acted as a lubricant and prolong the period of quasi-constant viscosity of the pastes.     

Study of release kinetics and diffusion coefficients in swellable cellulosic thin films by means of a simple spectrophotometric technique

Measurement of diffusion in gel is an essential task for pharmaceutic technology and biochemical engineering. In this work we investigate diffusion coefficients and release kinetics of colored substances loaded in polymeric thin strips, by extending a simple spectrophotometric technique from catalysis science to swellable polymer matrices. Absorbance can be a measure of the average solute concentration in the swollen gel so that the time decay of film absorbance can be a quantitative measure of the release kinetics and henceforth of the diffusion coefficient in the swollen gel. Thin film dissolution is carried out in a newly proposed microfluidic continuous flow-through device. Hydroxypropyl methylcellulose (HPMC) is used as filming polymer. Film thickness, uniformity of content and swelling time-scales are accounted for in the estimation of the effective diffusion coefficient.     

Influence of pore distribution on the equivalent thermal conductivity of low porosity ceramic closed-cell foams

The microstructures of porous alumina materials with different porosities were established by introducing the departure factor of pore position and acentric factor of pore diameter to describe the distribution of pores in space and in size, respectively. The contribution of radiation and influence of pore distribution on the equivalent thermal conductivity were discussed based on numerical simulations by the finite volume method (FVM) considering both thermal conduction and radiation. When the pore diameter was less than 10?µm, the radiation component was less than 2%, and radiation could be neglected. Radiative heat transfer played a dominant role for materials with high porosity and large pore size at high temperatures. For micro pore materials (<?100?µm), broad pore size and non-uniform pore space distribution decreased the thermal conductivity across the entire temperature range. For materials with macro pores (>1?mm), broad pore distribution decreased the thermal conductivity at low temperatures and increased it at high temperatures. The basic prediction model of effective thermal conductivity for a two-component material, the Maxwell–Eucken model (ME1) and its modified model were corrected by introducing the pore structure factor. The results from experiments prove that the numerical values were satisfactory.