Anhydrous Calcium Phosphate Research Articles

Enhancing the Antibacterial Properties of Magnesium Alloys with Copper-Doped Anhydrous Calcium Phosphate Nanoparticles Embedded into the Polycaprolactone Coating for Medical Implants

Enhancing the Antibacterial Properties of Magnesium Alloys with Copper-Doped Anhydrous Calcium Phosphate Nanoparticles Embedded into the Polycaprolactone Coating for Medical Implants

Anhydrous calcium phosphate crystals stabilize DNA for dry storage.

The resilience of ancient DNA (aDNA) in bone gives rise to the preservation of synthetic DNA with bioinorganic materials such as calcium phosphate (CaP). Accelerated aging experiments at elevated temperature and humidity displayed a positive effect of co-precipitated, crystalline dicalcium phosphate on the stability of synthetic DNA in contrast to amorphous CaP. Quantitative PXRD in combination with SEM and EDX measurements revealed distinct CaP phase transformations of calcium phosphate dihydrate (brushite) to anhydrous dicalcium phosphate (monetite) influencing DNA stability.

Characterization and modeling of the viscoelasticity of pharmaceutical tablets.

Evolution of the compaction properties of powders with the compaction speed (strain rate sensitivity, SRS) is a common phenomenon during the manufacturing of pharmaceutical tablets. Nevertheless, several different phenomena can be responsible of the SRS like friction, viscoelasticity, viscoplasticity or air entrapment. In this work, an original experimental methodology was developed to characterize specifically the viscoelasticity of tablets using a compaction simulator. After various compressions, tablets were finally loaded elastically at different constant strain rates. This methodology made it possible to measure the apparent bulk and shear moduli as a function of the strain rate. The methodology was successfully applied to microcrystalline cellulose (MCC), Starch, Lactose monohydrate (GLac) and Anhydrous Calcium Phosphate (ACP). No significant evolution of the moduli was found for Lac and ACP as expected. On the contrary, for MCC and Starch, both shear and bulk moduli were found to increase along with the strain rate. The viscoelastic behavior was then successfully modeled using prony series. Assessment of the model parameters was achieved by inverse identification using an analytical model and a finite element analysis.

Preparation, characterization and bioactivities of nano anhydrous calcium phosphate added gelatin–chitosan scaffolds for bone tissue engineering

Gelatin, chitosan and nano calcium phosphate based composite scaffold with tailored architectures and properties has great potential for bone regeneration. Herein, we aimed to improve the physico chemical, mechanical and osteogenic properties of 3D porous scaffold by incorporation of dihydrogen calcium phosphate anhydrous (DCPA) nanoparticles into biopolymer matrix with variation in composition in the prepared scaffolds. Scaffolds were prepared from the slurry containing gelatin, chitosan and synthesized nano DCPA particle using lyophilization technique. DCPA nano particles were synthesized using calcium carbonate and phosphoric acid in water–ethanol medium. XRD pattern showed phase pure DCPA in synthesized nanopowder. Scaffolds were prepared by addition of DCPA nanoparticles to the extent of 5–10 wt% of total polymer into gelatin–chitosan solution with solid loading varying between 2.5 and 2.75 wt%. The prepared scaffold showed interconnected porosity with pore size varying between 110 and 200 micrometer. With addition of DCPA nanoparticles, average pore size of the prepared scaffolds decreased. With increase in nano ceramic phase content from 5 wt% to 10 wt% of total polymer, the compressive strength of the scaffold increased. Scaffold containing 10 wt% DCPA showed the highest average compressive strength of 2.2 MPa. Higher cellular activities were observed in DCPA containing scaffolds as compared to pure gelatin chitosan scaffold suggesting the fact that nano DCPA addition into the scaffold promoted better osteoblast adhesion and proliferation as evident from MTT assay and scanning electron microscopic (SEM) investigation of osteoblast cultured scaffolds. A higher degree of lamellopodia and filopodia extensions and better spreading behavior of osteoblasts were observed in FESEM micrographs of MG 63 cultured DCPA containing scaffold. The results demonstrated that both mechanical strength and osteogenic properties of gelatin–chitosan scaffold could be improved by addition of anhydrous dihydrogen calcium phosphate nanoparticles into it.

Synthesis and thermal dehydroxylation kinetic of anhydrous calcium phosphate monetite CaHPO4

In this study, we have synthesized and performed the thermal decomposition kinetics of anhydrous calcium phosphate monetite CaHPO4 under air atmosphere by TG/DTG and DTA techniques using non-isothermal experiments. The prepared and calcined products at 500 °C were characterized by powder X-ray diffraction, infrared spectroscopy, transmission electron microscopy and X-ray microanalysis. The degradation of CaHPO4 was observed between [425–490 °C] and leads to the formation of calcium pyrophosphate by condensation of orthophosphate groups. The kinetic parameter results achieved by the isoconversional methods combined to Malek’s procedure showed that the thermal dehydroxylation is a single-step process which related to crystal nucleation and growth mechanism, according to JMA (n) model, with n = 1.37 and an activation energy of Friedman E α = 299.4 ± 2.1 kJ mol−1. The thermodynamic functions (ΔS*, ΔH* and ΔG*) of the thermal dehydroxylation step were calculated using the activated complex theory. The obtained values showed that the reaction is directly related to the introduction of heat and is non-spontaneous process.

Investigating the effect of tablet thickness and punch curvature on density distribution using finite elements method

Finite elements method was used to study the influence of tablet thickness and punch curvature on the density distribution inside convex faced (CF) tablets. The modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous calcium phosphate and microcrystalline cellulose) by using Drucker–Prager Cap model in Abaqus® software. The parameters of the model were obtained from experimental tests.Several punch shapes based on industrial standards were used. A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with a diameter of 8mm were chosen. Different tablet thicknesses were studied at a constant compression force.The simulation of the compaction of CF tablets with increasing thicknesses showed an important change on the density distribution inside the tablet. For smaller thicknesses, low density zones are located toward the center. The density is not uniform inside CF tablets and the center of the 2 faces appears with low density whereas the distribution inside FF tablets is almost independent of the tablet thickness.These results showed that FF and CF tablets, even obtained at the same compression force, do not have the same density at the center of the compact. As a consequence differences in tensile strength, as measured by diametral compression, are expected. This was confirmed by experimental tests.

To study physical compatibility between dibasic calcium phosphate and cohesive actives using powder rheometer and thermal methods

Aim: An attempt is made to provide better understanding of the compatibility aspect of excipients with different properties of active pharmaceutical ingredient (API) using various rheological, thermal and morphological studies conducted on binary mixtures of Dibasic Calcium Phosphate anhydrous (DCP-A) and Dibasic Calcium Phosphate dihydrate (DCP-D) forms with cohesive API’s (Acetaminophen and Aspirin).Method: Binary mixtures of DCP’s were prepared by addition of 0% w/w to 50% w/w of the API in each powder blend. Powder rheological analysis were conducted using FT4 powder rheometer, rotational shear cell and empirical approaches such as angle of repose (AOR), Hausner ratio (HR) and Carr’s index (CI). Thermal analysis was conducted using differential scanning calorimetry (DSC) and thermal effusivity. Morphological studies were conducted using Scanning Electron Microscopy (SEM) to determine the fundamental differences between powder materials.Result/Conclusions: Powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API’s than empirical approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D while such interaction was absent in DCP-A. Binary mixtures prepared using DCP-D were better flowable while blends containing DCP-A were better in stability (physical), compressibility and permeability. This study allows the scientist to understand the powder packing of different blends with their flowability and compressibility parameter and helps selection of appropriate form of hydrate for relevant API.

Formulation and manufacture of pharmaceuticals by fluidized‐bed impregnation of active pharmaceutical ingredients onto porous carriers

A manufacturing method is presented for solid dosage forms using fluidized‐bed impregnation, which could eliminate many of the challenges during solid dosage manufacturing. The main difference between impregnation and dry blending is the placement of the active pharmaceutical ingredient (API) inside a porous carrier. This makes the final material flow properties independent of the physical properties of the API. The method consists of spraying an API solution in appropriate solvent onto a carefully chosen porous excipient in a fluidized state. The solution penetrates the porous carrier due to capillary forces and the solvent is evaporated soon after that. Impregnation and drying occur simultaneously, which makes this impregnation method suitable for continuous implementation. Carefully choosing the operating conditions allows impregnation to occur without introducing spray drying or spray coating of the API. The method is shown to generate an impregnated excipient with very high degree of homogeneity independent of the API loading. It is also shown that mild milling further improves blend uniformity to RSD levels below 1%, which are challenging to achieve using conventional techniques. On impregnation, the final physical properties of the material are seen to be mainly unchanged from the initial excipient properties. A study of this one‐step manufacturing method is described, using acetaminophen as the model drug and anhydrous calcium phosphate dibasic as the porous excipient. The experimental work presented establishes a proof of concept and investigates in detail blend uniformity, physical state of impregnated API, final physical properties of impregnated material, compressibility during tableting, capsule filling, and release profile of the final capsule formulation. It also discusses potential ways for drug release control and improvements using impregnation. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4538–4552, 2013

The surface layer of pharmaceutical compacts: The role of the punch surface and its impact on the mechanical properties of the compacts

During pharmaceutical compaction, the interaction between the punch and the powder determines the formation and the aspect of the surface of the compact. In industry, the properties of the punch surface, which play a key role in this interaction, are sometimes changed by fixing an intermediate layer onto the punch to prevent sticking problems. In this article, the case of a polymer insert layer was studied. Firstly, sugar spheres were compacted with and without the polymer insert fixed onto the punches. After compaction with uncovered punches, the surface particles, which had been subjected to high deformation, were flattened on one side. However, it was observed, using confocal X-ray microfluorescence, that this kind of deformation was limited to the surface and that the bulk particles, which underwent a more isotropic deformation, still exhibited an approximately round shape. Secondly, the influence of the surface structure on the mechanical properties of the compacts was studied. The indentation hardness and the tensile strength of compacts of microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP) were studied. No differences were found for the compacts of MCC produced with the two kinds of punches, but the compacts of aCP obtained with uncovered punches presented a higher hardness and a higher tensile strength than those obtained with covered punches.

Measurements of Elastic Moduli of Pharmaceutical Compacts: A New Methodology Using Double Compaction on a Compaction Simulator

The elastic properties of pharmaceutical powders play an important role during the compaction process. The elastic behavior can be represented by Young's modulus (E) and Poisson's ratio (v). However, during the compaction, the density of the powder bed changes and the moduli must be determined as a function of the porosity. This study proposes a new methodology to determine E and v as a function of the porosity using double compaction in an instrumented compaction simulator. Precompression is used to form the compact, and the elastic properties are measured during the beginning of the main compaction. By measuring the axial and radial pressure and the powder bed thickness, E and v can be determined as a function of the porosity. Two excipients were studied, microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP). The values of E measured are comparable to those obtained using the classical three-point bending test. Poisson's ratio was found to be close to 0.24 for aCP with only small variations with the porosity, and to increase with a decreasing porosity for MCC (0.23-0.38). The classical approximation of a value of 0.3 for ν of pharmaceutical powders should therefore be taken with caution.

Negative intercepts in the Heckel analysis of the crude extract of Vernonia galamensis: A major setback of the equation

Introduction: The dry powdered leaf of Vernonia galamensis (Asteraceae) has been used by traditional herbalists in northern Nigeria to treat diabetes mellitus. However, medicinal plants used in folk medicine have no standard dose or acceptable method of formulation. In this study therefore, the leaves of Vernonia galamensis (Asteraceae) were extracted, evaluated for pharmacological activity and formulated into tablets. Materials and Methods: The extract was found to be highly hygroscopic and deliquescent, therefore the following efflorescent diluents; aerosil® 200 (GmbH, Meggle, Germany), avicel PH 101 (Honey Well and Stein, UK), and anhydrous calcium phosphate (BDH chemicals, England) were used. The wet granulation method was employed for the tablet formulation and the compaction characteristics of the granules were determined using the Heckel equation. Results and Conclusions: Negative intercepts were a setback to the use of the Heckel equation due to the resulting negative values of D A and D B . This makes it difficult to explain the compaction characteristics of the crude extract.

Anisotropic Porous Structure of Pharmaceutical Compacts Evaluated by PGSTE-NMR in Relation to Mechanical Property Anisotropy

The pore space anisotropy of pharmaceutical compacts was evaluated in relation to the mechanical property anisotropy. The topology and the pore space anisotropy were characterized by PGSTE-NMR measurements. Parallelepipedical compacts of anhydrous calcium phosphate (aCP) and microcrystalline cellulose (MCC) were tested on top, bottom and side faces. A microindentation and three-point single beam tests were used to measure Brinell hardness, tensile strength and Young's modulus. All the data were submitted to a statistical analysis to test for significance. The porous structure of MCC compacts was anisotropic, contrary to those of aCP. The analysis of the pore space by PGSTE-NMR method showed that its structural anisotropy was controlled by the behaviour under compaction of the excipients. At the same time, the Young's modulus and the tensile strength were the same whatever the direction of testing. For the aCP compacts, all the faces had the same Brinell hardness. With MCC compacts, only the bottom face showed a lower Brinell hardness. Except for Brinell hardness measured on MCC compacts, the tested samples were characterized by anisotropic mechanical properties when its porous structures were sometimes anisotropic. Then, there is not a straight link between porosity anisotropy and mechanical properties.

Changes in the specific surface area of tablets composed of pharmaceutical materials with various deformation behaviors

Objective: The aim of this work is to study the effect of compaction on the specific surface area of tablets composed of various pharmaceutical materials (microcrystalline cellulose, lactose, and anhydrous calcium phosphate) compacted under seven degrees of compaction pressure. Methods: In a first part, the influence of the deformation behavior of the compacted materials on the evolution of the specific surface area is observed. In a second part, the brittle and ductile abilities of the materials are calculated using the specific surface area values. The experimental results are used to calculate the number and the force of interparticulate bonds inside the tablet.Results and Discussion: Tablets made of microcrystalline cellulose, which deform plastically, have specific surface areas that fall under pressure. In the case of lactose, the tablet specific surface area first increases to reach a maximum value at a pressure of 150 MPa. At higher pressure, however, the specific surface area decreases. The specific surface area of tablets composed of anhydrous calcium phosphate consistently increases, whatever the compaction pressure applied. Moreover, the evolution of the specific surface area is correlated with the tensile strength of the corresponding tablets. The number and the force of interparticulate bonds make it possible to classify the materials according to their deformation behavior and to quantify their ability to form cohesive tablets.

The transformation of single-crystal calcium phosphate ribbon-like fibres to hydroxyapatitespheres assembled from nanorods

Two precursors of ribbon-like anhydrous dicalcium phosphate(DCPA) and calcium phosphate fibres were successfully synthesized at85 °C through a simple andmild pathway from Ca(NO3)2·4H2O and (NH4)2HPO4 upon the hydrolysis of urea. Different molar concentrations of urea resulted indifferent precursors, including precursor I (DCPA phase) and precursor II (calciumphosphate with DCPA, octacalcium phosphate (OCP) and hydroxyapatite (HAp)phase). By immersing the two precursors in ammonium hydroxide solution(pH = 12), the transformation from precursors to hydroxyapatite could be achieved. X-raydiffraction (XRD) results combined with transmission electron microscopy (TEM)indicated that DCPA fibres (precursor I) were transformed to HAp nanorods intransformation I. In transformation II, dandelion-like spheres assembled by HAp nanorodswere obtained from calcium phosphate (precursor II). The mechanisms of transformations Iand II are also proposed and discussed based on the XRD and TEM results.

Application of PGSTE-NMR technique to characterize the porous structure of pharmaceutical tablets

Direct compaction of pharmaceutical tablets is a complex process that results in a heterogeneous density distribution inside the compact. In the present study, we have used a non-invasive and non-destructive technique: the pulsed-gradient stimulated-echo (PGSTE) NMR method to access to topological information (connectivity, tortuosity) about the porous structure of the tablets obtained with three different pharmaceutical excipients: the microcrystalline cellulose, the lactose and the anhydrous calcium phosphate. These materials were chosen since their mechanical properties under pressure are highly differentiated. To probe the pore space with the PGSTE-NMR technique, the tablets were initially impregnated with silicone oil that is NMR sensitive ( 1H NMR). The time-dependent apparent self-diffusion coefficient was measured over a suitable range of diffusion time in the directions perpendicular and parallel to the compression axis, from which the tortuosity factor and the anisotropy of the porous structure can be studied. These results show that the porous structure varies with pressure and depends on the excipient behaviour under pressure. Then, this work demonstrates that PGSTE-NMR could be an alternative and a very interesting technique to obtain useful information on the structural properties of such compacted materials.

Application of percolation model to the tensile strength and the reduced modulus of elasticity of three compacted pharmaceutical excipients

Percolation theory has been applied to several mechanical properties of pharmaceutical tablets. This power law describes the change of tablet’s properties with the relative density. It defines critical tablet densities from which the mechanical properties start to change. The exponent in the law is expected to be universal for a mechanical property and numerical values are proposed in the literature. In this work, the percolation model was applied to the tensile strength and the reduced modulus of elasticity (obtained from surface indentation test) of three compacted pharmaceutical excipients (a microcrystalline cellulose, a lactose and an anhydrous calcium phosphate). Two approaches were proposed. First, the exponent was kept constant and equal to the values used in the literature (2.7 for the tensile strength and 3.9 for the reduced modulus of elasticity). Secondly, the critical tablet density ( i. e. the percolation threshold) and the exponent were determined from the model. In the first approach, the percolation thresholds were higher than the relative tapped density. Using the second approach, the experimentally determined exponents were not close to the values of the literature and the critical relative densities were higher than the relative tapped density or equal to zero. Then, this study showed that the exponent seems not universal and that the model must be used carefully.

Silylated calcium phosphates and their new behavior for copper retention from aqueous solution

Anhydrous calcium phosphate (CaP) was modified by surface silylation using three organosilanes (H 3CO) 3SiR, where R corresponds to the organic moieties CH 2CH 2CH 2NH 2, CH 2CH 2CH 2NHCH 2CH 2NH 2 and CH 2CH 2CH 2NHCH 2CH 2NHCH 2CH 2NH 2, originating nanomaterials named CaPSil1, CaPSil2, and CaPSil3. The products were characterized by elemental analysis, infrared spectroscopy, X-ray diffraction, thermogravimetry and 31P and 13C NMR. The amounts of attached amino groups on surfaces were 0.32 ± 0.05, 0.54 ± 0.04, and 1.21 ± 0.04 mmol g −1 for CaPSil x ( x = 1–3), respectively. Suspended silanized phosphates adsorbed copper cations from aqueous solution at liquid/solid interface.

Transition of laser-treated dental enamel

The application of lasers in clinical dental practice is becoming increasingly popular, because of the painless, time-saving, and easy-handling treatment of teeth. However, it is still not clear what really happens with the atomic structure of hydroxyapatite under laser irradiation. To study this issue, different spatial areas of laser-treated human enamel and synthetic hydroxyapatite were investigated by Raman and attenuated total reflectance infraredmicro-spectroscopy. The laser-treatment parameters were close to those used in clinical practice. The spectra were collected from spatial areas showing different laser-induced morphological alteration. Inside the laser crater anhydrous calcium phosphate phases are formed, as the degree of structural transformation depends on the applied laser power. In the periphery of the laser spot an exchange of CO3 2to CO2 occurs. When higher laser power is applied, an exchange of molecular groups embedded in hydroxyapatite was detected. In addition, the enhancement of the IR absorption typical for grain-surface OH groups suggests a decrease in the long-range order of apatite crystallites in the periphery of the laser spot. Comparison of spectroscopic data on laserand thermallytreated enamel reveals that inside and in the vicinity of the laser impact region the temperature can reach 1100 K and 700K, respectively. The utilization of super-pulse rather than continuous-wave irradiation mode results in a higher degree of structural alteration and inhomogeneity. m19.p04

Investigation and modelling approach of the mechanical properties of compacts made with binary mixtures of pharmaceutical excipients

Three pharmaceutical excipients (microcrystalline cellulose, lactose, anhydrous calcium phosphate) and their binary mixtures were compacted to form compacts of various mean porosities. Some mechanical properties (Young’s modulus, tensile strength and Brinell hardness) were studied on these compacts. The mechanical properties of the binary mixtures were not proportional to the mixture composition expressed in mass. More, for all the properties, a negative deviation was always observed from this linear relationship. In reference to a composition percolation phenomenon, critical mass fractions were detected from the graph mechanical property vs. mass composition of a mixture. The results obtained with Brinell hardness differed from the results of the Young’s modulus and the tensile strength, i.e. the most plastic material in the binary mixture controlled the mixture behaviour. Secondly, a predictive model based on a statistical approach was proposed for the Young’s modulus and the tensile strength. The validity of this model was verified on experimental data, and an interaction parameter used to characterize the affinity of the two compounds was calculated. Finally, the X-ray tomography technique was applied to the compacts of cellulose/phosphate mixtures to obtain cross-sections images of the compacts. The analysis of the cross-sections images allowed explaining the no linear relationship of the different mechanical properties results observed on these binary mixtures.

Compaction behaviour and new predictive approach to the compressibility of binary mixtures of pharmaceutical excipients

The compressibility of three pharmaceutical excipients (microcrystalline cellulose, lactose and anhydrous calcium phosphate) and their binary mixtures was studied. The aim of this work was to observe the impact of the mass composition of the mixture on the compressibility. The single-compound materials and their mixtures were compacted using instrumented presses. It allowed obtaining compression cycles (i.e., force–displacement curves) which were associated with energy measurements (specific compaction energy, E sp cp and specific expansion energy, E sp exp ). It was observed that for the mixtures studied, the change of E sp cp with the mass composition could be fitted using a linear relationship (it was not the case with E sp exp ). A linear relationship between the porosity of mixture’s compacts and the mass composition was also obtained. Heckel’s plots were then obtained for the three excipients and the mixtures. The mean yield pressure was calculated with the “in-die-method” and the “out-of-die method”. A proportional relationship was not valid for the mean yield pressures. But, a predictive approach was proposed in order to obtain indirectly the mean yield pressure of a binary mixture if the data of the single materials were known. It used the linear mixing rule observed with the porosity. The validity was verified and compared with the experimental values. This comparison showed that it was possible to predict the mean yield pressure of binary mixtures from the accessible data of the single excipients.