Inert Cores Research Articles

Dissolution Profile of Novel Composite Pellet Cores Based on Different Ratios of Microcrystalline Cellulose and Isomalt

There is a growing interest towards the application of inert cores as starting materials for pharmaceutical pellet manufacturing. They serve as alternatives to develop and adapt a relatively simple manufacturing technology compared with an extrusion/spheronisation process. The major objective of this study was to investigate the effect of the compositions of core materials on the drug release profile. Pure microcrystalline cellulose (MCC), isomalt and different types of novel composite MCC-isomalt cores were layered with model drug (sodium diclofenac) and were coated with acrylic polymer. The effect of the osmolality in the gastrointestinal tract was simulated using glucose as osmotically active agent during in vitro dissolution tests. The results demonstrated the dependence of drug dissolution profile on the ratio of MCC and isomalt in the core and the influence of osmotic properties of the dissolution medium. Isomalt used in the composite core was able to decrease the vulnerability of the dissolution kinetics to the changes in the osmotic environment.

Pelletization by Extrusion Spheronization Technique: An Excipient Review

Pellets/spheres have gained wide popularity amongst solid dosage forms due to numerous advantages offered by their spheroid nature and each pellet acting as a seperate drug delivery device. At an industrial scale, pellets are manufactured by extrusion-spheronization technique (ES) however, alternative techniques are also available. Such pellets obtained may be used as neutral or drug loaded pellets. Till date, microcrystalline cellulose (MCC) was considered as a golden standard for ES. Prior to MCC, sugar pareils were used as inert cores for drug loading. But due to physicochemical interactions of MCC, and technological difficulties faced during processing of MCC and sugar pellets, the need for the search of newer excipients as a pelletization aid has been triggered. To name a few, chitosan, carrageenan, starch, pectin, talc etc are being explored. The present review is an attempt to take account of the excipients used to design multiple unit particulate systems (MUPS) by ES technique and propose prospective excipient combinations to overcome limitations of existing pellets and excipients thereof. Keywords: Excipients, extrusion-spheronization, microcrystalline cellulose, pellets, pelletization techniques, prospective excipients.

Pelletization by Extrusion Spheronization Technique: An Excipient Review

Pellets/spheres have gained wide popularity amongst solid dosage forms due to numerous advantages offered by their spheroid nature and each pellet acting as a seperate drug delivery device. At an industrial scale, pellets are manufactured by extrusion-spheronization technique (ES) however, alternative techniques are also available. Such pellets obtained may be used as neutral or drug loaded pellets. Till date, microcrystalline cellulose (MCC) was considered as a golden standard for ES. Prior to MCC, sugar pareils were used as inert cores for drug loading. But due to physicochemical interactions of MCC, and technological difficulties faced during processing of MCC and sugar pellets, the need for the search of newer excipients as a pelletization aid has been triggered. To name a few, chitosan, carrageenan, starch, pectin, talc etc are being explored. The present review is an attempt to take account of the excipients used to design multiple unit particulate systems (MUPS) by ES technique and propose prospective excipient combinations to overcome limitations of existing pellets and excipients thereof. Keywords: Excipients, extrusion-spheronization, microcrystalline cellulose, pellets, pelletization techniques, prospective excipients.

Novel Composite Spherical Granulates with Catalytic Outer Layer and Improved Conversion Efficiency and Selectivity

AbstractThe granulation procedure of a catalyst powder is a crucial step in designing a high‐quality catalyst granulate for industrial applications. New granulation processes have been developed that make it possible to form granulates with a very narrow particle size distribution and high sphericity. The innovative granulation techniques offer a great potential to produce layered catalysts with inert cores and an active shell. The novel spherical granules consist of an inexpensive inert core coated with an active catalyst material. New core shell granules with an accurately designed spherical geometry have been synthesized and compared to conventional homogeneous spherical granules of the same shape. The conversion of methanol to olefins has been used as a test reaction to validate the efficiency of these promising granulates.

Evaluation of Drug Release From Coated Pellets Based on Isomalt, Sugar, and Microcrystalline Cellulose Inert Cores

The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit RS30D and Eudragit RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles.

Formulation and evaluation of domperidone pellets prepared by powder layering technology

The goal of the present study is to evaluate the influence of the formulation and operating conditions on pellet preparation by the pan technique.The effect of initial core weight on the physical parameters of pellets as well as to conduct stability study was also the goal of this study. For this domperidone maleate was selected as the model drug. Pellets were prepared by layering of powdered drug on sugar-based cores. Inert cores were intermittently treated with micronized drug powder and binding solution. This treatment led to the formation of multiple layers of drug particles around an inert core resulting in the production of pellets that can further be coated by different polymers to obtain modified release formulations. Scanning electron microscopy was employed to image the surface morphology of the prepared pellets. Drug loading efficiency, % yield, size, and shape uniformity of pellets were increased along with increasing the initial core weight. Drug content and dissolution study were performed by following HPLC and UV–Visible method. About 50% and 80% drug was released within 7.72 m and 13.66 m respectively in 0.1N HCl media (pH 1.2). Physical appearance of the prepared pellets, potency, moisture content, pellets size and shape, dissolution data, release rate constant, diffusion exponent (P<.05) over the stability period showed that the system is efficient for the production of highly stable formulations. This study also showed the good performance of the conventional coating pan system in obtaining instant release domperidone pellets prepared by the powder layering technique.

Three-body Faddeev like approach to direct nuclear reactions

Momentum space three-body Faddeev-like equations are used to calculate elastic, transfer and charge exchange reactions resulting from the scattering of deuterons on 12 C and 16 O or protons on 11 Be, 13 C and 17 O; 10 Be, 12 C and 16 O are treated as inert cores. All possible reactions are calculated in the framework of the same model space. Comparison with previous calculations based on approximate methods used in nuclear reaction theory is discussed.

Three-body Faddeev-Alt-Grassberger-Sandhas approach to direct nuclear reactions

Momentum-space three-body Faddeev-like equations are used to calculate elastic, transfer, and charge-exchange reactions resulting from the scattering of deuterons on {sup 12}C and {sup 16}O or protons on {sup 13}C and {sup 17}O, with {sup 12}C and {sup 16}O treated as inert cores. All possible reactions are calculated in the framework of the same model space. Comparison with previous calculations based on approximate methods used in nuclear reaction theory is made.

Design and in Vitro/in Vivo Evaluation of Multi-layer Film Coated Pellets for Omeprazole

The purpose of the study is to perform the in vitro and in vivo evaluation of multi-layer film coatings for omeprazole. The system consists of drug-layered or drug-containing core pellets coated with salt (sodium chloride and disodium hydrogen phosphate), hydroxypropyl methyl cellulose (HPMC), and enteric film-coating layer, respectively. The drug-layered core pellets were prepared by a coating layer of omeprazole on inert pellet cores in fluidized bed coater. An in vitro/in vivo gastro-resistance study was conducted, and a dissolution study was performed in pH 7.4 phosphate buffer for omeprazole release. The multi-layer coated pellets were stable in gastric pH conditions and upper gastrointestinal (GI) tract in rats. Salt layer improved the drug stability, and its coating levels had little influence on the dissolution profiles of omeprazole. The rate of drug release was significantly delayed by HPMC layer. The salt layer could function as a separated layer, and substitute part of the HPMC layer and decrease the coating levels of HPMC. The bioavailability (AUC) of the multi-layer coated drug-layered and drug-containing pellets was 3.48+/-0.86 and 2.97+/-0.57 microg*h/ml, respectively. The drug-layered pellets with multi-layer film coatings not only provided delayed and rapid release of omeprazole, but also could provide a good stable property for omeprazole. It was confirmed that rapid in vitro drug release rate resulted in better absorption.

Dissolution behavior of metals from particulate matter emissions*

Exposure to air particulate matter (PM) is linked to numerous health effects. In order to improve the understanding of the role of its metallic components, their solubility was examined by using serial short-contact dissolutions totalling 1 h and additional sequential contact periods of 1, 4, and 8 days. The dissolution experiments were performed in solutions containing the main biological electrolytes. ICPMS determinations were used to quantify the dissolved metals. The total compositions were determined after closed vessel microwave digestion. Large variations in the rate and completeness of the dissolutions were observed. Fast and extensive dissolutions within the short-contact time (e.g., Zn, Cd) as well as slow dissolutions persisting during the last contact period (e.g., Ni, Cu, Sb, Pb) were found for smelting emissions. The multi-element determinations also made it possible to identify relationships between dissolution of different metals and define gradual composition changes of residual PM. When comparing with dissolutions performed in de-ionized water, similar major fractions were observed at short-contact time for minor components of smelting or combustion emissions (e.g., V, Ni, Cd), suggesting a preponderance of easily available forms at the surface of the relatively inert particle cores. The use of these time sequential methods may help in (1) modeling metal partitioning in biological media and (2) investigating the causes of adverse effects attributed to air PM. This work was presented in part at the 2006 Winter Conference on Plasma Spectrochemistry, January 8–14, 2006, Tucson, USA.

Conformal Coating of Mammalian Cells Immobilized onto Magnetically Driven Beads

A novel cell bead system, comprising a magnetic core, a spherical annulus of agarose-immobilized cells, all conformally coated within a synthetic polymer, is proposed as a means of immunoisolating mammalian cells in a system that provides a balance between low total implant volume, retrievability, and diffusion limitations. A successful immunoisolation system could be used to transplant cells without eliciting an inappropriate host response. Chinese hamster ovary (CHO) cells were immobilized at the periphery of large (approximately 2 mm) agarose beads containing inert magnetic cores (< or = 1 mm) and coated in a hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymer by interfacial precipitation. The beads were coated in liquid gradients containing polyethylene glycol 200 (PEG) or bromooctane. Although many cells were adversely affected by the coating process, the cells that did survive (30-50% of those loaded into the beads) remained viable for a period of at least 2 weeks. This viability was much higher than achieved previously because of a number of factors, such as the aqueous agarose, the hydrophobic bromooctane intermediate layer, and faster coating times that minimize the exposure of the cells to organic solvents. Also, a mathematical model was used to describe oxygen transport within the annular agarose beads. These results provide evidence that the proposed geometry and the fabrication approach may be useful for a variety of applications that involve cell encapsulation.

Experimentalgfactors andB(E2)values of21+,41+,22+, and31−states inZn64andZn68compared to shell model predictions

The g factors of the short-lived 2{sub 1}{sup +},4{sub 1}{sup +}, and 3{sub 1}{sup -} states in {sup 64}Zn and the 2{sub 1}{sup +},4{sub 1}{sup +},2{sub 2}{sup +}, and 3{sub 1}{sup -} states in {sup 68}Zn have been measured using the combined technique of projectile Coulomb excitation in inverse kinematics and transient magnetic fields. In addition, B(E2)'s have been deduced from remeasured lifetimes of several excited states employing the Doppler-shift-attenuation method. Whereas the present data for the 2{sub 1}{sup +} states agree very well with our previous results, the g factors of the other states have been determined for the first time. All experimental data were compared with results from large-scale shell model calculations based on proton and neutron configurations in the fp and fpg model spaces with {sup 40}Ca and {sup 56}Ni as inert cores, respectively.

Description of the single-particle motions around two inert cores(Poster presentation,YITP Workshop on New Developments in Nuclear Self-Consistent Mean-Field Theories (MF05))

Description of the single-particle motions around two inert cores(Poster presentation,YITP Workshop on New Developments in Nuclear Self-Consistent Mean-Field Theories (MF05))

Products and Mechanisms of Ozone Reactions with Oleic Acid for Aerosol Particles Having Core−Shell Morphologies

Heterogeneous reactions of oleic acid aerosol particles with ozone are studied below 1% relative humidity. The particles have inert polystyrene latex cores (101-nm diameter) coated by oleic acid layers of 2 to 30 nm. The chemical content of the organic layer is monitored with increasing ozone exposure by using an aerosol mass spectrometer. The carbon-normalized percent yields of particle-phase reaction products are 20−35% 9-oxononanoic acid, 1−3% azelaic acid, 1−3% nonanoic acid, and 35−50% other organic molecules (designated as CHOT). There is approximately 25% evaporation, presumably as 1-nonanal. To explain the formation of CHOT molecules and the low yields of azelaic and nonanoic acids, we suggest a chemical mechanism in which the Criegee biradical precursors to azelaic acid and nonanoic acid are scavenged by oleic acid to form CHOT molecules. These chemical reactions increase the carbon-normalized oxygen content (z/x) of the CxHyOz layer from 0.1 for unreacted oleic acid to 0.25 after high ozone exposure. Under the assumption that oxygen content is a predictor of hygroscopicity, our results suggest an increased cloud condensation nuclei activity of atmospherically aged organic particles that initially have alkene functionalities.

Measurements ofgfactors and lifetimes of low-lying states in62–70Znand their shell model implication

The g factors of the first ${2}^{+}$ states and the $B(E2)$ values of the ${(2}_{1}^{+}\ensuremath{\rightarrow}{0}_{1}^{+})$ transitions have been determined with high precision for all stable doubly even Zn isotopes employing the combined technique of projectile Coulomb excitation in inverse kinematics and transient magnetic fields. In addition, this systematic study was supplemented by a first measurement of radioactive ${}^{62}\mathrm{Zn}$ ${(T}_{1/2}=9.2 h)$ formed in an $\ensuremath{\alpha}$-transfer reaction with a ${}^{58}\mathrm{Ni}$ beam. The ${g(2}_{1}^{+})$ values obtained are in good agreement with previous data but provide considerably higher accuracy. The same quality of agreement was found for the $B(E2)$ values with the exception of ${}^{70}\mathrm{Zn}$ where the measured value is slightly smaller. The experimental data were compared with large scale shell model calculations considering configurations in the $\mathrm{fp}$ and $\mathrm{fpg}$ model spaces with inert cores of ${}^{40}\mathrm{Ca}$ and ${}^{56}\mathrm{Ni},$ respectively.

Measurements ofgfactors and lifetimes of low lying states in58–64Niand their shell model implications

The g factors of the first ${2}^{+}$ states and the $B(E2)$ values of the ${(2}_{1}^{+}\ensuremath{\rightarrow}{0}_{1}^{+})$ transitions have been determined with high precision for all stable doubly even Zn isotopes employing the combined technique of projectile Coulomb excitation in inverse kinematics and transient magnetic fields. In addition, this systematic study was supplemented by a first measurement of radioactive ${}^{62}\mathrm{Zn}$ ${(T}_{1/2}=9.2 h)$ formed in an $\ensuremath{\alpha}$-transfer reaction with a ${}^{58}\mathrm{Ni}$ beam. The ${g(2}_{1}^{+})$ values obtained are in good agreement with previous data but provide considerably higher accuracy. The same quality of agreement was found for the $B(E2)$ values with the exception of ${}^{70}\mathrm{Zn}$ where the measured value is slightly smaller. The experimental data were compared with large scale shell model calculations considering configurations in the $\mathrm{fp}$ and $\mathrm{fpg}$ model spaces with inert cores of ${}^{40}\mathrm{Ca}$ and ${}^{56}\mathrm{Ni},$ respectively.

Structure of excited states of10Bestudied with antisymmetrized molecular dynamics

We study structure of excited states of 10Be with the method of variation after spin parity projection in the framework of antisymmetrized molecular dynamics. Present calculations describe many excited states and reproduce the experimental data of E2 and E1 transitions and the new data of the $\beta$ transition strength successfully. We make systematic discussions on the molecule-like structures of light unstable nuclei and the important role of the valence neutrons based on the results obtained with the framework which is free from such model assumptions as the existence of inert cores and clusters.

Variation after Angular Momentum Projection for the Study of Excited States Based on Antisymmetrized Molecular Dynamics

In order to study the structure of excited states we perform a variational calculation after spin parity projection (VAP) within the framework of Antisymmetrized Molecular Dynamics (AMD). The framework is proven to be a new powerful approach for the study of the various structures of excited states because it is free from model assumptions such as inert cores, existence of clusters, and the axial symmetry. By using finite range interactions with a density dependent term we reproduce well all the energy levels below 15 MeV in $^{12}$C. This is the first theoretical model that reproduces many $E2$ transition rates and $\beta$ decays to $^{12}$C successfully.

Pellets as a dosage form for drugs in aquaculture: technological aspects

Fish feed pellets are usually manufactured by extrusion of a steam-conditioned meal. However, since high temperatures are involved in this process, it is often not suitable for incorporation of drugs. The pharmaceutical industry uses a variety of pelletization techniques to cope with this problem. To the pharmaceutical industry, pellets are spherical particles with a diameter between 0.25 and 1.5 mm. The most popular pharmaceutical pelletization processes nowadays are the layering of drugs onto inert cores and the extrusion-spheronization process. Other processes such as the wet granulation technique in the rotary processor seem to be promising. This wet granulation technique in the rotary processor was used to produce pellets containing a gonadotropin-releasing hormone analogue and penetration enhancers. This pellet formulation was able to induce ovulation in fish.

Combined dipyridamole and aspirin pellet formulation for improved oral drug delivery. Part 1: Development pharmaceutics.

The dissolution profile of various weight fractions of dipyridamole: hydropropylmethylcellulose acetate succinate (HPMC-AS) and dipyridamole: hydroxypropylmethylcellulose phthalate co-precipitates lead to the choice of 1:2 dipyridamole: HPMC-AS as the controlled-release component. It was deposited to form two-third of the total dose as an inner layer on inert sucrose cores by air suspension coating for release mainly in the small intestine. Further examination of this material by IR spectroscopy, differential scanning calorimetry and X-ray diffraction indicated some free drug, preferentially soluble under gastric pH conditions. One-third of the total dose was applied by pan coating as an outer layer of micronized dipyridamole around the inner enteric co-precipitate layer. Aspirin-loaded cores were prepared also by pan coating for use in the final product, which contained both anti-platelet drugs.