The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

The Effects of Formulation Factors on the Moist Granulation Technique for Controlled-Release Tablets

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied. Dissolution testing was carried out in distilled water using the USP paddle method. In all cases, the granules flowed and compressed well. The granule properties were evaluated by calculating the mean particle size for all batches from sieve analysis data. The results indicate that MGT can be applied to control drug release, and at a polymer content of 44.6% or more, the process is robust enough to allow slight variations in formulation factors without affecting drug release.     

Synthesis of high intensity green emitting (Ba,Sr)SiO4:Eu2+ phosphors through cellulose assisted liquid phase precursor process

Green emitting phosphor (Ba_1−x,Sr_1−x)SiO₄:2xEu²⁺, x = 0.03, 0.05, 0.1, and 0.15 were synthesized through a Liquid Phase Precursor Process (LPP). Liquid phase precursor method is reported to result in phosphors with markedly increased emission intensities compared to other synthesis methods. Here microcrystalline cellulose (MCC) and hydroxypropyl cellulose (HPC) templates were studied to achieve high efficiency green phosphors. The phase formation was investigated by XRD analysis which showed the conformation of the Ba₂SiO₄ (JCPDS card number 761631) phase. The obtained samples exhibited broad excitation spectra with maximum at 430 nm and a green emission centered around 520 nm. An optimized dopant concentration was selected and the effect of two different types of cellulose, i.e. MCC and HPC templates on the emission properties was considered. It was found that the samples synthesized using HPC and fired at 1050 °C under a reducing atmosphere, showed a high intensity of almost 2 times that of the MCC sample. Further experiments were conducted by varying viscosity, particle weight, and molecular weight of the HPC template. It was found that the green emission from the (Ba,Sr)SiO₄:Eu²⁺ increased with the increase in viscosity and molecular weight of the template.     

Discrimination of matrix–fibre interactions in all-cellulose nanocomposites

All-cellulose nanocomposites are produced using dissolved microcrystalline cellulose (MCC) as the matrix and cellulose nanowhiskers (CNWs), produced by acid hydrolysis, as the reinforcement. These nanocomposites are then characterised using X-ray diffraction to determine their crystallinity, and Raman spectroscopy to discriminate the reinforcing phase (cellulose I) from the CNWs and the matrix phase (cellulose II) from the dissolved MCC. Mechanical testing of the composites shows that there is a significant systematic reinforcement of the matrix material with the addition of CNWs. Furthermore, Raman spectroscopy is used to show that distinct spectroscopic bands for each phase within the composite spectrum can be used to discriminate the effects of both reinforcement and matrix. It is shown that a Raman band located approximately at 1095 cm⁻¹ can be used to follow the micromechanical deformation of the CNWs and matrix, whereas another band located at 895 cm⁻¹ arises purely from the matrix. This spectroscopic fingerprint is used to gain insights into the complex interactions occurring in these potentially recyclable composite materials, and offers a way forward to optimising their properties.     

Cellulose nanocrystal-filled carboxymethyl cellulose nanocomposites

Polymer nanocomposites are one of the important application areas for nanotechnology. Naturally derived organic nanophase materials are of special interest in the case of polymer nanocomposites. Carboxymethyl cellulose is a polyelectrolyte derived from natural materials. It has been extensively studied as a hydrogel polymer. Methods to modify the mechanical properties of gels and films made from CMC are of interest in our lab and in the commercial marketplace. The effect of nano-sized fillers on the properties of CMC-based composites is of interest in the development of novel or improved applications for hydrogel polymers in general and CMC in particular. This project investigated cellulose nanocrystals (CNXLs) as a filler in CMC and compared the effects to microcrystalline cellulose (MCC). The composite material was composed of CMC, MCC or CNXL, with glycerin as a plasticizer. CNXL and MCC concentrations ranged from 5% to 30%. Glycerin concentrations were kept constant at 10%. CNXLs improved the strength and stiffness of the resulting composite compared to MCC. In addition, a simple heat treatment was found to render the nanocomposite water resistant.     

Thermo-mechanical properties of innovative microcrystalline cellulose filled composites for art protection and restoration

Microcrystalline cellulose (MCC) powder was selected as a natural reinforcement for a commercial acrylic adhesive widely used in the field of art protection and restoration (Paraloid B72). In particular, various amounts (from 5 to 30 wt%) of MCC were melt compounded with Paraloid B72 to prepare new thermoplastic polymer composites for the cultural heritage conservation field. Scanning electron microscopy showed that MCC flakes are uniformly dispersed within the matrix at all the tested compositions, without preferential orientation. Thermogravimetric analysis evidenced an increase of thermal stability due to the MCC introduction, even at low filler amounts, while DSC measurements demonstrated that the glass transition temperature progressively increases with the MCC content. Interestingly, DMTA analysis revealed a stabilizing effect on the material produced by microcellulose addition, with an increase of the storage modulus and a decrease of the thermal expansion coefficient, in proportion to the filler loading. Moreover, MCC addition determined an increase of the elastic modulus and creep stability with respect to the neat resin, and an enhancement of fracture toughness (K _IC).     

A novel approach of developing micro crystalline cellulose reinforced cementitious composites with enhanced microstructure and mechanical performance

This paper reports a novel approach of preparing aqueous suspensions of microcrystalline cellulose (MCC) for fabrication of cementitious composites. MCC was dispersed homogeneously in water using Pluronic F-127 as a surfactant with the help of ultrasonication process and the aqueous suspensions were added to cement/sand mixture to prepare cementitious composites. A commonly used stabilizing agent for MCC, carboxy methyl cellulose (CMC) was also used for the comparison purpose. The prepared suspensions were characterized through visual inspection, UV-Vis spectroscopy and optical microscopy. The developed composites were characterized for their bulk density, flexural and compressive properties as well as microstructure. The influence of Pluronic and CMC concentration, superplasticizer, dispersion technique and dispersion temperature on mortar's mechanical performance was thoroughly studied to find out the optimum conditions. Overall, Pluronic (with Pluronic: MCC ratio of 1:5) led to better MCC dispersion as well as dispersion stability as compared to CMC. The best mechanical performance was achieved with Pluronic in combination with superplasticizer using ultrasonication process, resulting in improvement of 106%, 31% and 66% in flexural modulus, flexural strength and compressive strengths, respectively (highest values reported till date). The bulk density and hydration of cementitious composites also improved significantly with the addition of MCC.     

Use of a Moist Granulation Technique (MGT) to Develop Controlled-Release Dosage Forms of Acetaminophen

The moist granulation technique (MGT), which involves agglomeration and moisture absorption, has only been applied to immediate-release dosage forms. Our results indicate that MGT appears to be applicable in developing a controlled-release formulation. A small amount of granulating fluid (water) was added to a powder blend to activate a dry binder (such as polyvinylpyrrolidone [PVP] at 2% and 3.6%) and to facilitate agglomeration. Then, a moisture-absorbing material (microcrystalline cellulose [MCC]) was added to absorb any excess moisture. By adding MCC in this way, a drying step was not necessary. Acetaminophen (APAP) was the model drug, with diluents lactose FastFlo® and dicalcium phosphate. Hydroxypropylcellulose (HPC) was used as the controlled-release agent. The MGT was compared to conventional wet granulation (WG) and direct compression (DC) processing methods. The results indicate that MGT appears to be applicable in developing a controlled-release formulation. Particle size distribution of MGT and WG batches containing 3.6% PVP is similar.     

Use of a Moist Granulation Technique (MGT) to Develop Controlled-Release Dosage Forms of Acetaminophen

The moist granulation technique (MGT), which involves agglomeration and moisture absorption, has only been applied to immediate-release dosage forms. Our results indicate that MGT appears to be applicable in developing a controlled-release formulation. A small amount of granulating fluid (water) was added to a powder blend to activate a dry binder (such as polyvinylpyrrolidone [PVP] at 2% and 3.6%) and to facilitate agglomeration. Then, a moisture-absorbing material (microcrystalline cellulose [MCC]) was added to absorb any excess moisture. By adding MCC in this way, a drying step was not necessary. Acetaminophen (APAP) was the model drug, with diluents lactose FastFlo® and dicalcium phosphate. Hydroxypropylcellulose (HPC) was used as the controlled-release agent. The MGT was compared to conventional wet granulation (WG) and direct compression (DC) processing methods. The results indicate that MGT appears to be applicable in developing a controlled-release formulation. Particle size distribution of MGT and WG batches containing 3.6% PVP is similar.     

In Vitro Performance of Floating Sustained-Release Capsule of Verapamil

Abstract

Capsules filled with mixtures of verapamil, hydroxypropoxyl cellulose (HPC), and effervescent are proposed to provide floating sustained release over 10 hr. The effects of weight filled in the capsule, amount of HPC, and the addition of effervescent on the dissolution kinetics are studied. The conventional capsules were filled with different amounts and weights of the mixtures of verapamil, HPC, and effervescent. The release of verapamil from the capsules followed the Higuchi release model. However, when effervescent was added, a zero-order drug release was observed after the burst phase. The conventional capsule, when filled with active ingredients, polymers, and effervescent, can achieve a zero-order release system. Entrapped air was considered as a barrier to diffusion and matrix relaxation in drug release.     

A study on water adsorption onto microcrystalline cellulose by near-infrared spectroscopy with two-dimensional correlation spectroscopy and principal component analysis

Water adsorption onto microcrystalline cellulose (MCC) in the moisture content (M(c)) range of 0.2-13.4 wt % was investigated by near-infrared (NIR) spectroscopy. In order to distinguish heavily overlapping O-H stretching bands in the NIR region due to MCC and water, principal component analysis (PCA) and generalized two-dimensional correlation spectroscopy (2DCOS) were applied to the obtained spectra. The NIR spectra in four adsorption stages separated by PCA were analyzed by 2DCOS. For the low M(c) range of 0.2-3.1 wt %, a decrease in the free or weakly hydrogen-bonded (H-bonded) MCC OH band, increases in the H-bonded MCC OH bands, and increases in the adsorbed water OH bands are observed. These results suggest that the inter- and intrachain H-bonds of MCC are formed by monomeric water molecule adsorption. In the M(c) range of 3.8-7.1 wt %, spectral changes in the NIR spectra reveal that the aggregation of water molecules starts at the surface of MCC. For the high M(c) range of 8.1-13.4 wt %, the NIR results suggest that the formation of bulk water occurs. It is revealed from the present study that approximately 3-7 wt % of adsorbed water is responsible for the stabilization of the H-bond network in MCC at the cellulose-water surface.     

Analytical approaches to improved characterization of substitution in hydroxypropyl cellulose

Chemical characterization of cellulose derivatives is of high importance as it provides information about the often inhomogeneous substitution that may seriously affect the properties of these polymers in various applications. A detailed mapping of the chemical structure of these derivatives requires several advanced techniques to be employed. In this study, the average substitution and the substitution heterogeneity in two hydroxypropyl cellulose (HPC) samples from different suppliers were studied by means of NMR spectroscopy, MALDI-TOF MS, and HPAEC-PAD. (1)H and (13)C NMR provided information on the molar substitution, a parameter that could be analyzed by MALDI-TOF MS as well. In addition, the latter technique was used for determination of the distribution of the number of hydroxypropyl groups per glucose unit present in the two polymers. The heterogeneity of the substitution was studied by determining the amount of unsubstituted glucose units in the HPC samples, which was accomplished by HPAEC-PAD analysis. The results obtained suggest that the two HPC samples differ in both hydroxypropoxy content and distribution of the hydroxypropyl groups. Further, the benefits and importance of employing several analytical methods when investigating the cellulose ether substitution are demonstrated, as each method provides different kinds of information on the chemical content.     

An in-depth analysis of Raman and near-infrared chemical images of common pharmaceutical tablets

This study reports on the application of Raman and near-infrared (NIR) imaging techniques for determining the spatial distribution of all (five) components in a common type of pharmaceutical tablet manufactured in two different ways. Multivariate chemical images were produced as principal component (PC) scores, while univariate images were produced by using the most unique spectra selected by the orthogonal projection approach (OPA), a searching algorithm. Multivariate Raman images were obtained for all five components in both tablets, while only two or three components could be imaged with the NIR instrument. Very interesting PC results are reported that in effect cast doubt on the effectiveness of the established criteria for determining signal-related PCs in the Raman data. PCA has been found to be indispensable for imaging the minor components using the Raman data. Significant similarity between the multivariate and univariate chemical images has been noted despite there being considerable spectral overlap within the Raman and, especially, within the NIR mapping data sets. Gray-scale images are carefully thresholded, which allowed for quantitative comparison of the obtained binarized images. A thorough discussion is given on the problems and approximations needed for producing composite images.     

Development of fast-disintegrating pellets in a rotary processor

The aim of the present work was to formulate fast-disintegrating pellets by direct pelletization in a rotary processor. Formulations containing kaolin or bentonite and lactose were agglomerated with or without the addition of crospovidone in an instrumented rotary processor. The effects of the excipients on the amount of wall adhesion, the size and size distribution, the disintegration time, and the shape of the agglomerates, as well as the content of agglomerates > 2800 microns, were investigated. Further, pellets containing a model drug having a low aqueous solubility were prepared, and the drug dissolution profile was compared to that of pellets containing microcrystalline cellulose (MCC). Formulations containing kaolin resulted in fast-disintegrating pellets. Pellets containing bentonite eroded, but did not disintegrate, and the formulations gave rise to large amounts of wall adhesion. The addition of crospovidone increased the water content at the end of liquid addition for all formulations, and resulted in slightly more spherical agglomerates. When comparing formulations containing kaolin and MCC, kaolin gave rise to wider size distributions and a higher amount of agglomerates > 2800 microns, but the drug dissolution rate was much faster. Complete (100%) drug release was seen after 8 min with the kaolin formulation, whereas only 40% was released after 2 hr from the MCC formulation.     

Analyzing Raman maps of pharmaceutical products by sample-sample two-dimensional correlation

Sample-sample (SS) two-dimensional (2D) correlation spectroscopy is applied in this study as a spectral selection tool to produce chemical images of real-world pharmaceutical samples consisting of two, three, and four components. The most unique spectra in a Raman mapping spectral matrix are found after analysis of the covariance matrix. (This is obtained by multiplying the original mapping data matrix by itself.) These spectra are identified by analyzing the slices of the covariance matrix at the positions where covariance values are at maxima. Chemical images are subsequently produced in a univariate fashion by visually selecting the wavenumbers in the extracted spectra that are least overlapped. The performance of SS 2D correlation is compared with principal component analysis in terms of highlighting the most prominent spectral differences across the whole data set (which typically comprises several thousand spectra) and determining the total number of species present. In addition, the selection of the unique spectra by SS 2D correlation is compared with the selection obtained by the orthogonal projection approach (OPA). Both comparisons are found to be satisfactory and demonstrate that a quite simple SS 2D correlation routine can be used for producing reliable images of unknown samples. The main benefit of using SS 2D correlation is that it is based on a few data processing commands that can be executed separately and produce results that are closely related to the chemical features of the system.     

微晶纤维素的活化对其溶解性能的影响

用胺活化、水活化与超声波活化分别处理了微晶纤维素(MCC)。研究了活化前后微晶纤维素在氢氧化钠-尿素-硫脲中的溶解时间、聚合度、溶解度、纤维表面形态、结晶度以及对分子氢键的影响。结果表明,超声波活化较其他2种活化方法效果更好,且处理功率为60%～99%、处理时间在60～120min内更有利于改善微晶纤维素的溶解性能。     

Vibrational spectroscopic studies and density functional theory calculations of speciation in the CO2-water system

Raman spectra of CO(2) dissolved in water and heavy water were measured at 22 degrees C, and the Fermi doublet of CO(2), normally at 1285.45 and 1388.15 cm(-1) in the gaseous state, revealed differences in normal water and heavy water, although no symmetry lowering of the hydrated CO(2) could be detected. Raman spectra of crystalline KHCO(3) and KDCO(3) were measured at 22 degrees C and compared with the infrared data from the literature. In these solids, (H(D)CO(3))(2)(2-) dimers exist and the spectra reveal strong intramolecular coupling. The vibrational data of the dimer (C(2h) symmetry) were compared with the values from density functional theory (DFT) calculations and the agreement is fair. Careful measurements were made of the Raman spectra of aqueous KHCO(3), and KDCO(3) solutions in D(2)O down to 50 cm(-1) and, in some cases, down to very low concentrations (> or =0.0026 mol/kg). In order to complement the spectroscopic assignments, infrared solution spectra were also measured. The vibrational spectra of HCO(3)(-)(aq) and DCO(3)(-)(D(2)O) were assigned, and the measured data compared well with data derived from DFT calculations. The symmetry for HCO(3)(-)(aq) is C(1), while the gas-phase structure of HCO(3)(-) possesses Cs symmetry. No dimers could be found in aqueous solutions, but at the highest KHCO(3) concentration (3.270 mol/kg) intermolecular coupling between HCO(3)(-)(aq) anions could be detected. KHCO(3) solutions do not dissolve congruently, and with increasing concentrations of the salt increasing amounts of carbonate could be detected. Raman and infrared spectra of aqueous Na(2) -, K(2) -, and Cs(2)CO(3) solutions in water and heavy water were measured down to 50 cm(-1) and in some cases down to extremely low concentrations (0.002 mol/kg) and up to the saturation state. For carbonate in aqueous solution a symmetry breaking of the D(3h) symmetry could be detected similar to the situation in aqueous nitrate solutions. Strong hydration of carbonate in aqueous solution could be detected by Raman spectroscopy. The hydrogen bonds between carbonate in heavy water are stronger than the ones in normal water. In sodium and potassium carbonate solutions no contact ion pairs could be detected even up to the saturated solutions. However, solvent separated ion pairs were inferred in concentrated solutions in accordance with recent dielectric relaxation spectroscopy (DRS) measurements. Quantitative Raman measurements of the hydrolysis of carbonate in aqueous K(2)CO(3) solutions were carried out and the hydrolysis degree a was determined as a function of concentration at 22 degrees C. The second dissociation constant, pK(2), of the carbonic acid was determined to be equal to 10.38 at 22 degrees C.     

Single-molecule detection using surface-enhanced resonance Raman scattering and Langmuir-Blodgett monolayers

The Langmuir-Blodgett (LB) technique has been used to obtain spatially resolved surface-enhanced resonance Raman scattering (SERRS) spectra of single dye molecules dispersed in the matrix of a fatty acid. The experimental results presented here mimic the original electrochemical surface-enhanced Raman scattering (SERS) work where the background bulk water did not interfere with the detection of the SERS signal of molecules adsorbed onto the rough silver electrode. LB monolayers of the dye in fatty acid have been fabricated on silver island films with a concentration, in average, of one probe molecule per micrometer square. The properties of single-molecule spectroscopy were investigated using micro-Raman including mapping and global images. Blinking of the SERRS signal was also observed.     

Evaluation of hydroxypropyl methylcellulose phthalate 50 as film forming polymer from aqueous dispersion systems

Hydroxypropyl methylcelluose phthalate 50 (HPMCP 50) was evaluated as a film forming polymer from aqueous dispersion systems. The influence of plasticizer type and level on the elasticity of HPMCP 50 free films prepared by the casting method was studied by measuring Young's modulus using an Instron Material Testing System. The release of a water soluble drug in various dissolution media from pellets coated with HPMCP 50 with 30% plasticizer containing various levels of hydroxypropyl cellulose (HPC) or hydroxypropyl methylcellulose (HPMC) was also studied. The influence of coating level on drug release from pellets was also investigated. Results showed that HPMCP 50 alone without a plasticizer does not form a film. However, when a plasticizer was added HPMCP 50 did form a film. Also, as the concentration of the plasticizer triethyl citrate was increased the elasticity of HPMCP 50 films was increased. Similar results were obtained with the plasticizer diethyl phthalate. For pellets a high coating level was required to achieve adequate protection in 0.06 N HCl. Drug release from coated pellets was found to be dependent upon the type and the level of the water soluble polymer incorporated with HPMCP 50. Drug release was increased as the percentage of HPC was increased. Higher release rates were obtained with HPMC compared to HPC. Coating level significantly influenced drug release in 0.06 N HCl; however, less of an effect was observed at pH 5.5.