Cellulose Phosphate Research Articles

Processing-induced-transformations (PITs) during direct compression: Impact of tablet composition and compression load on phase transition of caffeine

In the pharmaceutical field, solid-state transitions that may occur during manufacturing of pharmaceuticals are of great importance. The phase transition of a model API, caffeine Form I (CFI), was studied during direct compression process by analysing the impacts of the operating conditions (process and formulation). This work is focused on two formulation parameters: nature of the diluent and impact of the caffeine dilution, and one process parameter: the compression pressure that may impact the phase transition of CFI. Tablets were made from pure CFI and from binary mixture of CFI/diluent (microcrystalline cellulose or anhydrous dicalcium phosphate). A kinetic study performed during six months helped to highlight the influence of these parameters on the CFI transition degree. Results showed a triggering effect of the direct compression process, transformation was higher in tablets than in uncompressed powders. Whatever the pressure applied, CFI transition degree was almost constant and uniformly occurring throughout the tablet volume. Nevertheless, several differences on the evolution of the CFI transition degree were observed between binary mixtures of CFI/diluent. An analysis of the transition mechanism with a stretched exponential law of the Johnson-Mehl-Avrami model shows that tableting accelerates the polymorphic transition without modifying its mechanism controlled by nucleation only.

Development of new phosphated cellulose for application as an efficient biomaterial for the incorporation/release of amitriptyline

In the last years has increased the study about the using of natural biopolymers and theirs derivatives in the removal (adsorption/incorporation) of contaminats of medium aqueous, and theirs utilization in the desorption (release) de drugs. However, there not in the literature studies about the utilization of the cellulose and cellulose phosphate in the adsorption (incorporation)/desorption (release) of the drug amitriptyline (AMI). Therefore, in this study was accomplished the synthesized of the phosphated cellulose (PC) through the reaction of pure cellulose (C) with sodium trimetaphosphate (P) under-reflux, for 4h and at 393K. The efficiency of the reaction was observed by XRD, TG/DTG, 31P NMR and EDS. The adsorption study for the AMI in aqueous medium was carried out by varying the time, pH, concentration, temperature and ionic strength. The results showed that the PC showed a greater adsorption capacity of AMI than pure cellulose, presenting an increase of about 102.72% in the adsorption capacity of the drug by cellulose after the phosphating reaction. In desorption of drug from the surface of biomaterials was performed by varying the pH and time, where it was observed that PC showed a maximum release of 40.98%±0.31% at pH 7.

Adsorption Behavior of Cellulose and Its Derivatives toward Ag(I) in Aqueous Medium: An AFM, Spectroscopic, and DFT Study.

The aim of this study was to develop a fundamental understanding of the adsorption behavior of metal ions on cellulose surfaces using experimental techniques supported by computational modeling, taking Ag(I) as an example. Force interactions among three types of cellulose microspheres (native cellulose and its derivatives with sulfate and phosphate groups) and the silica surface in AgNO3 solution were studied with atomic force microscopy (AFM) using the colloidal probe technique. The adhesion force between phosphate cellulose microspheres (PCM) and the silica surface in the aqueous AgNO3 medium increased significantly with increasing pH while the adhesion force slightly decreased for sulfate cellulose microspheres (SCM), and no clear adhesion force was observed for native cellulose microspheres (CM). The stronger adhesion enhancement for the PCM system is mainly attributed to the electrostatic attraction between Ag(I) and the negative silica surface. The observed force trends were in good agreement with the measured zeta potentials. The scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) analyses confirmed the presence of silver on the surface of cellulose microspheres after adsorption. This study showed that PCM with a high content of phosphate groups exhibited a larger amount of adsorbed Ag(I) than CM and SCM and possible clustering of Ag(I) to nanoparticles. The presence of the phosphate group and a wavenumber shift of the P-OH vibration caused by the adsorption of silver ions on the phosphate groups were further confirmed with computational studies using density functional theory (DFT), which gives support to the above findings regarding the adsorption and clustering of Ag(I) on the cellulose surface decorated with phosphate groups as well as IR spectra.

Formulation Development and Evaluation of Gabapentin Controlled Release Tablets

The objective of the present study was to develop a pharmaceutically equivalent, stable, robust, cost effective and quality improved formulation of Gabapentin controlled release tablets by using different grades of controlled release polymer. The design of dosage form was performed by choosing Hydroxypropyl Methyl Cellulose (HPMC K100MCR), Hydroxypropyl Methyl Cellulose (HPMC K15MCR), Microcrystalline Cellulose (MCC) and Di-calcium phosphate polymers as matrix builders. The drug-polymer compatibility studies were performed. Blend Uniformity was studied and accordingly the flowability was optimized for the powder blend. Tablets were prepared by direct compression with free flowing powder. The network formed by HPMC, MCC and DCP had been coupled satisfactorily with the controlled resistance, in vitro release and FT-IR. Mean dissolution time was also reported to compare various dissolution profiles. The formula was finalized by comparing the in vitro dissolution with that of the innovator SR and IR tablets. Optimized formulation of Gabapentin was formulated using 23% HPMC K100MCR and 10% of DCP. In vitro drug release profile was examined 98.69% within 12h. The releases of the formulation were fitting to Hixson Crowell model suggesting controlled zero order release from the formulation. The results suggested that direct compression is a suitable method to formulate controlled release Gabapentin tablets and it can perform therapeutically better than conventional immediate release dosage form.

Production of cellulose phosphate from oil palm empty fruit bunch: Effect of chemical ratio

Cellulose phosphate was synthesized from oil palm biomass residue that has the potential to represent a considerable added value product for the oil palm biomass utilization. Cellulose phosphate (CP) is prepared viaa phosphorylation process using the H3PO4/P2O5/Et3PO4/hexanol sequence using oil palm empty fruit bunch microcrystalline cellulose (OPEFB-MCC) as the starting material. Various factors affect its synthesis; one of them which is the subject of this investigation is the orthophosphoric acid (H3PO4) to triethylphosphate(Et3PO4) ratio which have the capability to increase the phosphorus content of CP. It is believed that during this reaction, the esterification of the free hydroxyl groups of the cellulose occurred. The H3PO4/Et3PO4 ratios applied were 0.16, 1.00, and 1.84. The effect of the H3PO4/Et3PO4 ratio on phosphorus content, yield, water swelling and molecular structure of CP are discussed.

Layer-by-layer hybrid films of phosphate cellulose and electroactive polymer as chromium (VI) sensors

Hybrid and electroactive thin films containing microcrystalline cellulose (MC) or MC modified with a phosphate group (PC) were prepared in conjunction with polyaniline (PANI) and poly(vinyl sulfonic acid) (PVS) by the layer-by-layer technique. The MC or PC was dispersed in a PANI solution employed in the deposition process, and they produced the PVS/PANI(MC) and PVS/PANI(PC) films. The ultraviolet-visible (UV-Vis) studies showed that the same amount of material was adsorbed at each stage of deposition, characterizing the PVS/PANI(MC) and PVS/PANI(PC) films as self-regulated systems. The electrochemical measurements and cyclic voltammetry were carried out in a buffered medium and showed that PVS/PANI(PC) films present higher values of current density probably due to the self-doping process of polyaniline in the presence of phosphate cellulose. The PVS/PANI(PC) film was tested in the presence of chromium VI, and in this case, the presence of a third reduction peak at 0.38 V was observed, which is characteristic of this metal, demonstrating the possibility of PVS/PANI(PC) as an active layer in the development of sensors for monitoring groundwater springs.

Validation and applications of an expedited tablet friability method

The harmonized monograph on tablet friability test in United States Pharmacopeia (USP), European Pharmacopeia (Pharm. Eur.), and Japanese Pharmacopeia (JP) is designed to assess adequacy of mechanical strength of a batch of tablets. Currently, its potential applications in formulation development have been limited due to the batch requirement that is both labor and material intensive. To this end, we have developed an expedited tablet friability test method, using the existing USP test apparatus. The validity of the expedited friability method is established by showing that the friability data from the expedited method is not statistically different from those from the standard pharmacopeia method using materials of very different mechanical properties, i.e., microcrystalline cellulose and dibasic calcium phosphate dihydrate. Using the expedited friability method, we have shown that the relationship between tablet friability and tablet mechanical strength follows a power law expression. Furthermore, potential applications of this expedited friability test in facilitating systematic and efficient tablet formulation and tooling design are demonstrated with examples.

The Effectiveness of TBAF/DMSO in Dissolving Oil Palm Empty Fruit Bunch-Cellulose Phosphate

Oil Palm Empty Fruit Bunch (OPEFB), a waste from Oil Palm tree is the most waste products which can be found abundantly on earth that leads to contamination. Cellulose Phosphate (OPEFB-CP) which is derived from the process known as phosphorylation possesses good attribute to be diversified in bone graft functioning as natural polymer. Sol-gel process is chosen to produce porous bone scaffold where it is essential to the OPEFB-CP to get dissolved before reacting with coupling agent. The main problem for the natural polymer is, it cannot be melted or easily dissolved in any common or cheap solvents to be applied in various potential application. This paper will discuss specifically in dissolving the natural polymer by using Tetrabutyl Ammonium Flouride (TBAF) in Dimethyl Sulfoxide (DMSO) and analyzing results from FTIR. TBAF will be added into DMSO and heated and evenly stirred beginning at the lowest temperature, 600C and OPEFB-CP was added to the mixture solution until clear solution is produced. The characterization of cellulose solution from FTIR showed obvious different pattern with solid OPEFB-CP that proved cellulose was completely dissolved in mixture of TBAF/DMSO solution. FTIR results show no peak at wavenumbers 2385cm-1 but still remain two other peaks at wavenumbers 1377cm-1 and 1021cm-1. The observation obtained from the experimental works also concluded that the dissolution rate of cellulose is linear with the temperature increase starting from 600C with changes in the solution color.

Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver

The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. Compatibility studies are considered to be the first step in product development and on considering a biowaiver candidate these gain even greater importance since the final product will not be submitted to in vivo tests. The aim of this study was to qualitatively determine the composition of a commercially available fluconazole formulation in the form of capsules with regard to the presence of critical excipients and to carry out compatibility studies by differential scanning calorimetry (DSC). One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed; however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy that did not evidence any modification in the solid state characteristics.

Recovery and separation of rare Earth elements using salmon milt.

Recycling rare earth elements (REEs) used in advanced materials such as Nd magnets is important for the efficient use of REE resources when the supply of several REEs is limited. In this work, the feasibility of using salmon milt for REE recovery and separation was examined, along with the identification of the binding site of REEs in salmon milt. Results showed that (i) salmon milt has a sufficiently high affinity to adsorb REEs and (ii) the adsorption capacity of the milt is 1.04 mEq/g, which is comparable with that of commercial cation exchange resin. Heavier REEs have higher affinity for milt. A comparison of stability constants and adsorption patterns of REEs discussed in the literature suggests that the phosphate is responsible for the adsorption of REE in milt. The results were supported by dysprosium (Dy) and lutetium (Lu) LIII-edge extended x-ray absorption fine structure (EXAFS) spectroscopy. The REE-P shell was identified for the second neighboring atom, which shows the importance of the phosphate site as REE binding sites. The comparison of REE adsorption pattern and EXAFS results between the milt system and other adsorbent systems (cellulose phosphate, Ln-resin, bacteria, and DNA-filter hybrid) revealed that the coordination number of phosphate is correlated with the slope of the REE pattern. The separation column loaded with milt was tested to separate REE for the practical use of salmon milt for the recovery and separation of REE. However, water did not flow through the column possibly because of the hydrophobicity of the milt. Thus, sequential adsorption–desorption approach using a batch-type method was applied for the separation of REE. As an example of the practical applications of REE separation, Nd and Fe(III) were successfully separated from a synthetic solution of Nd magnet waste by a batch-type method using salmon milt.

ChemInform Abstract: Why Is Mannitol Becoming More and More Popular as a Pharmaceutical Excipient in Solid Dosage Forms?

AbstractReview: 42 refs.

Cellulose phosphorylation with a mixture of orthophosphoric acid and ammonium polyphosphate in urea medium

Cellulose samples with various extents of structural ordering (native cotton cellulose and mercerized cellulose) were phosphorylated with a mixture of orthophosphoric acid and ammonium polyphosphate in a urea medium. The phosphorus content and ion-exchange capacity of phosphorylated mercerized cellulose are higher than those of the initial natural polysaccharide phosphorylated under the same conditions. Modification of the glucopyranose rings of cellulose mainly occurs in amorphous regions of the polymer. The maximal rate of thermal degradation of cellulose phosphates is considerably lower than that of the initial polymers, and the degradation rate maximum is observed at 238–245°C, in contrast to the main process of dehydration and carbonization of the initial materials, occurring at 330–340°C. The results obtained can be used for preparing ion-exchange sorbents and fireproof fabrics with preset properties.

Technological Excipients of Tablets: Study of Flow Properties and Compaction Behavior

The physical properties of pharmaceutical powders/granules are very important in the development of oral solid dosage forms. The aim of this paper was, in a first stage, to carry out an evaluation of the flow properties (angle of repose, flow time, compaction capacity, compressibility index, Carr index and Hausner ratio) of technological or primary excipients of tablets (microcrystalline cellulose and dibasic calcium phosphate dihydrate) which behave differently during compaction, either pure and in binary mixtures, whose composition varied between 20% (w/w) and 80% (w/w) at intervals of 20% (w/w). In a second stage, using an instrumented eccentric tableting machine, energies and exerted forces during compaction of these materials were measured and the compressibility curves were registered. In addition, plasticity index and lubrication coefficient were calculated and weight uniformity, thickness, hardness and tensile strength of the manufactured tablets were also evaluated. The obtained results demonstrated that the binary mixtures and the pure excipients showed similar flow properties. On the other hand, the obtained tablets with the plastic excipient had lower values of exerted force by the upper punch and apparent net energy, and higher values of plasticity index and time periods of the force/time compression profiles.

Determination of mercury in river water by diffusive gradients in thin films using P81 membrane as binding layer

In this work, a device based on diffusive gradients in thin films (DGT) was evaluated for the determination of Hg(II) in river water. The DGT device was assembled with a cellulose phosphate ion exchange membrane (P81 Whatman) as a binding phase and agarose gel 1.5% (m/v) as a diffusive layer. Laboratory deployments showed that the binding of Hg2+ ([HgDGT]/[Hgsolution]) by P81 membrane was more effective (97%) than the Chelex 100 resin (80%).The effect of ionic strength, pH and potential interfering ions on Hg binding with DGT׳s was investigated. The results showed no significant effect on the binding of Hg(II) at pH range from 3.5 to 8.5 and at an ionic strength range from 0.0005 to 0.1molL−1. Uptakes of 50µgL−1 Hg(II) by P81 membrane were not affected by Fe, Mn, Zn, Cu, Ca and Mg at the concentration range of 200–1800µgL−1. Finally, the DGT device using the P81 as the binding layer was applied for in situ measurements of Hg in river water. For in situ measurements, the labile Hg concentration (from <2 to 13ngL−1) was lower than 10% of the dissolved fraction (from 155 to 446ngL−1).

Phosphorus-doped carbon derived from cellulose phosphate as efficient catalyst for air-cathode in microbial fuel cells

Phosphorus-doped (P-doped) carbon was prepared via direct pyrolysis of cellulose phosphate for efficient oxygen reduction catalyst in air-cathode of microbial fuel cells (MFCs). Air-cathodes with P-doped carbon catalysts were assembled by rolling method and their performances in MFCs were studied. A maximum power density of 1312 ± 82 mW m−2 was produced by air-cathode with P-doped carbon catalyst prepared at 1000 °C. This result was higher than the air-cathode with Pt/C catalyst and three times as that with P-free carbon catalyst derived from pure cellulose. This study demonstrated that the P-doped carbon derived from cellulose phosphate was a cost-efficient and promising cathodic catalyst for scale-up MFCs.

Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press

Context: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets.Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for tablet weight but significantly affect volume of powder inside the feeder in case of powders with excellent flowability (DCP). The opposite effect of paddle speed was observed for fairly flowing powders (MCC). Tableting speed played a role in weight and weight variability, whereas changing fill depth exclusively influenced tablet weight.Conclusion: The DoE approach allowed predicting the optimum combination of process parameters leading to minimum tablet weight variability. Monte Carlo simulations allowed assessing the probability to exceed the acceptable response limits if factor settings were varied around their optimum. This multi-dimensional combination and interaction of input variables leading to response criteria with acceptable probability reflected the design space.

Rapid Preparation of Biosorbents with High Ion Exchange Capacity from Rice Straw and Bagasse for Removal of Heavy Metals

This work describes the preparation of the cellulose phosphate with high ion exchange capacity from rice straw and bagasse for removal of heavy metals. In this study, rice straw and bagasse were modified by the reaction with phosphoric acid in the presence of urea. The introduced phosphoric group is an ion exchangeable site for heavy metal ions. The reaction by microwave heating yielded modified rice straw and modified bagasse with greater ion exchange capacities (∼3.62 meq/g) and shorter reaction time (1.5–5.0 min) than the phosphorylation by oil bath heating. Adsorption experiments towards Pb2+, Cd2+, and Cr3+ ions of the modified rice straw and the modified bagasse were performed at room temperature (heavy metal concentration 40 ppm, adsorbent 2.0 g/L). The kinetics of adsorption agreed with the pseudo-second-order model. It was shown that the modified rice straw and the modified bagasse could adsorb heavy metal ions faster than the commercial ion exchange resin (Dowax). As a result of Pb2+ sorption test, the modified rice straw (RH-NaOH 450W) removed Pb2+ much faster in the initial step and reached 92% removal after 20 min, while Dowax (commercial ion exchange resin) took 90 min for the same removal efficiency.

Isolation, purification, and identification of an important pigment, sepiapterin, from integument of the lemon mutant of the silkworm, Bombyx mori.

Sepiapterin is the precursor of tetrahydrobiopterin, an important coenzyme of aromatic amino acid hydroxylases, the lack of which leads to a variety of physiological metabolic diseases or neurological syndromes in humans. Sepiapterin is a main pigment component in the integument of the lemon mutant of the silkworm, Bombyx mori (L.) (Lepidoptera: Bombycidae), and is present there in extremely high content, so lemon is a valuable genetic resource to extract sepiapterin. In this study, an effective experimental system was set up for isolation and purification of sepiapterin from lemon silkworms by optimizing homogenization solvent, elution buffer, and separation chromatographic column. The results showed that ethanol was the most suitable solvent to homogenize the integument, with a concentration of 50% and solid:liquid ratio of 1:20 (g/mL). Sepiapterin was purified successively by column chromatography of cellulose Ecteola, sephadex G-25-150, and cellulose phosphate, and was identified by ultraviolet-visible absorption spectrometry. A stable and accurate high performance liquid chromatography method was constructed to identify sepiapterin and conduct qualitative and quantitative analyses. Sepiapterin of high purity was achieved, and the harvest reached about 40 ug/g of integument in the experiments. This work helps to obtaining natural sepiapterin in large amounts in order to use the lemon B. mori mutant to produce BH4 in vitro.

Optimization of cellulose phosphate synthesis from oil palm lignocellulosics using wavelet neural networks

Cellulose phosphate was synthesized from microcrystalline cellulose derived from oil palm lignocellulosics via the H3PO4/P2O5/Et3PO4/hexanol method. The influence of process variables (viz. temperature, reaction time, and the H3PO4/Et3PO4 ratio) on the properties of the resulting cellulose phosphate was investigated using a wavelet neural network model with the goals of ascertaining which factors were critical and of determining optimized reaction parameters for this synthesis. The experimental results corroborated the good fit of the wavelet neural network model. The prediction errors were quite small (less than 7%), and the regression values (R2 greater than 0.99) were also satisfactory.

A Novel Approach for Bone Scaffold from Oil Palm Empty Fruit Bunch-Cellulose Phosphate / Glass Material

Current trend has demonstrated the implementation of natural polymers as alternative materials in various engineering applications including biomaterials and biomedical applications. This paper reviews the potential of Cellulose Phosphate derived from Oil Palm Empty Fruit Bunch (OPEFB-CP) as a biomedical material. OPEFB-CP will act as reinforcement to glass materials in fabricating good and flexible scaffold composite materials. A 3-dimensional scaffold composite material comprised of the cellulose phosphate and glass material was produced by using a sol-gel technique. The composite biomaterial is expected to have degraded together as one material.