Multilayer Beads Research Articles

Colonial Glass Beads (16th-Cent.) from Indigenous Localities of the Tamtoc Peninsula (San Luis Potosí), Mexico

We have investigated two Nueva Cádiz tubular glass beads (16th-Century) from the indigenous localities of the Tamtoc Peninsula, Huasteca Potosina (Mexico). It was part of an exceptional discovery of 96 European glass beads found in archaeological contexts of the Early Colonial period (dated 14C 1512 AD ± 30 years, before 1560 AD). They correspond typologically to the Kidd's typology's colour variants IIIc1 and IIIc2. These multilayered beads are made from a gob formed by three successive dips, then blown up, drawn, and hot-formed before being sectioned. PIGE/PIXE (Particle-induced Induced Gamma and X-Ray Emissions) and Raman spectroscopy analyses reveal that the glass type is an ashes soda-lime-silica glass. Trace elements associated with the metal oxides used to tint and opacify these glasses are also significant. The outer layer of both types is blue-coloured by copper oxide while a mixture of tin and lead oxides opacifies the middle layer in white through cassiterite (SnO2) formation. As, Ni, Bi, and U contents reveal this cobalt, mixed with manganese, which colours the inner layer of type IIIc1 beads in purple, comes from the Freiberg mine in Southeastern Germany (Saxony). Compared with other Pan-American finds from the same period, these Mexican Nueva Cádiz beads have similar chemical compositions to specimens discovered in the colonial city ‘ruins of Nueva Cádiz (Cubagua Island, Venezuela). Finally, we question 16th-Century texts on how Mesoamerican peoples might have culturally perceived these blue beads made with a material unknown to them. By studying Mexico's colonial history, we propose several Spanish expeditions that may have introduced these beads to the Huasteca.

System identification and closed-loop control of laser hot-wire directed energy deposition using the parameter-signature-quality modeling scheme

Hot-wire directed energy deposition using a laser beam (DED-LB/w) is a method of metal additive manufacturing (AM) that has benefits of high material utilization and deposition rate, but parts manufactured by DED-LB/w suffer from a substantial heat input and undesired surface finish. Hence, regulating the process parameters and monitoring the process signatures to control the final quality during the deposition is crucial to ensure the quality of the final part. This paper explores the dynamic modeling of the DED-LB/w process and introduces a parameter-signature-quality modeling and control approach to enhance the quality of modeling and control of part qualities that cannot be measured in situ. The study investigates different process parameters that influence the melt pool width (signature) and bead width (quality) in single and multi-layer beads. The proposed modeling approach utilizes a parameter-signature model as F1 and a signature-quality model as F2. Linear and nonlinear modeling approaches are compared to describe a dynamic relationship between process parameters and a process signature, the melt pool width (F1). A fully connected artificial neural network is employed to model and predict the final part quality, i.e., bead width, based on melt pool signatures (F2). Finally, the effectiveness and usefulness of the proposed parameter-signature-quality modeling is tested and verified by integrating the parameter-signature (F1) and signature-quality (F2) models in the closed-loop control of the width of the part. Compared with the control loop with only F1, the proposed method shows clear advantages and bears potential to be applied to control other part qualities that cannot be directly measured or monitored in situ.

Wave energy harvesting based on multilayer beads integrated spherical TENG with switch triggered instant discharging for self-powered hydrogen generation

Effective strategies to gain hydrogen energy from harvesting and conversion from ocean energy attract extensive attention in the new energy source field. Remarkably, triboelectric nanogenerator (TENG) presents potential applications for harvesting large-scale blue energy from the ocean. Herein, we propose a self-powered hydrogen generation system by multilayer beads integrated spherical TENG with the power management system (PMS). The triggered switch used in the spherical TENG overcomes the limitation of working frequency through instantaneous driving, significantly improving the output performance and greatly expanding its application range. The six-layer beads integrated TENG presents a significant improvement in converting water wave energy into electric energy, and its power density reaches 21.3 W m−3 at 2 Hz. The integrated TENG charges 470 μF capacitor to 5 V in 200 s, and the hydrogen production rate is about 64.5 μL min−1 under the water wave condition, which overcomes the limitation of external power demands for conventional water electrolysis. Compared with the electrochemical cells driven by solar, our integrated system can operate in all weather conditions without an external power source. This work demonstrates the feasibility of the electrochemical conversion of low-frequency water wave energy into green energy.

Dual-responsive multilayer beads with zero leakage and controlled release triggered by near-infrared light

Multilayer beads made from biomacromolecules are useful for encapsulating, protecting, and delivering active ingredients such as drugs, dyes, and proteins. However, their encapsulated cargos are allowed to diffuse slowly out into the surrounding solvent during storage. This study describes a “smart” multilayer bead that can achieve zero leakage for encapsulated materials during storage and controlled release after triggered by near-infrared (NIR) light. The innermost layer of the multilayer bead containing Fe3O4 magnetic nanoparticles is prepared based on the thermal-responsive sol-gel transition of agar, which offers magnetic responsiveness to the bead. The middle layer of the bead embedding gold nanorods (Au NRs) is produced by the ionic crosslinking between alginate and terbium ions. Moreover, encapsulated materials (drugs, dyes, and agrochemicals) are loaded in the middle layer. The outermost layer of the bead, a paraffin-wax shell, is formed at 75 ℃ through the phase transition of paraffin wax. Because of the protection of the paraffin-wax shell, the encapsulated materials present zero leakage when the multilayer bead is placed in aqueous solutions for at least six weeks. Under the irradiation of 808 nm NIR light for 1 min, the multilayer bead is heated up to 50 ℃ by the photothermal effect of Au NRs in the middle layer, which triggers the melting of the paraffin-wax shell. Then, the controlled release of the encapsulated materials can be achieved by the rest of the bead. Furthermore, the bead can be recycled after the release due to its magnetic responsiveness. Consequently, the multilayer bead is a novel, green and economical candidate for diverse applications, especially for the encapsulation and controlled release of hydrophilic materials in bio-related applications.

Survival of potential probiotic isolated from fermented tea leaf and encapsulated in multilayer beads stored in makiang (Cleistocalyx nervosum var. paniala) juice

Cleistocalyx nervosum var. paniala juice or makiang juice has high content of acid and phenolic compounds which are detrimental to probiotic bacteria. The screening of potential probiotic with acid production and phenolic tolerant bacteria from fermented tea leaves revealed 5 isolates which were identified using 16s rRNA sequencing procedure and found similarity to the strain of Lactobacillus plantarum in GenBank database at 98–100%. The storage of 5 isolates and 6 probiotics in makiang juice for 24 h was indicated that L. plantarum MF105 and TISTR 2074 showed the least reduction of 30.10 ± 1.25 and 61.41 ± 2.37%, respectively. These cultures were encapsulated in 2% alginate bead (Al), Al + single-layer of gelatin (ACG), and Al + double-layer of gelatin (ACGD). They were kept in makiang juice at 4 °C. The physico-chemical characteristics of beads in makiang juice illustrated that the accumulation of phenolic compounds was faster than the pH decreasing and caused initial reduction of bacterial viability. The ACGD beads absorbed slower and accumulated less amount of phenolic compounds than others. They were the most effective in cell protection, the viability of encapsulated MF105 and TISTR2074 were prolonged to more than 7 and 4 days, respectively. Cell adaptation in combination with encapsulation enhanced the survival of probiotic cell in sub-lethal stress conditions. Data had shown that increasing the coating layer provided a chance to improve lethality of probiotic bacteria.

Parametric study and optimization of GMAW based AM process for Multi-layer bead deposition

Wire arc additive manufacturing (WAAM) is popularly becoming an important and cost-effective manufacturing process to fabricate medium-large size components. The process provides the ability to build a near-net-shape structure with a high production rate (50–130 gm/min) and high material usage efficiency (80–90%). However, as per other additive manufacturing (AM) processes, process planning and optimization provide a uniform, time-efficient, and defect-free deposition. Therefore, this study focuses on the parametric study and process optimization to fabricate multi-layers wall components. The most commonly and widely used SS304 stainless steel metallic wire has been used to fabricate four-layered wall structures using multi-layer bead deposition. Open circuit voltage (OCV); wire feed speed (WFR) and shielding gas flow rate (SGFR) has been selected as the input process parameters and the bead height to width ratio (H/W) selected as the output parameter. The nine experiments were performed using the L9 orthogonal array based on the Taguchi method and then implemented the analysis of variance (ANOVA) to describe various properties. The resultant data has been analyzed and studied using Minitab-17 software. The results obtained showed that the optimum condition for the H/W ratio is 24 V OCV, 14 m/min WFR, and 10Lit/min SGFR. The order of process parameters influencing the H/W ratio is OCV, WFR, and SGFR. These results were validated by conducting confirmation experiments and found satisfactory.

Geometry and Distortion Prediction of Multiple Layers for Wire Arc Additive Manufacturing with Artificial Neural Networks

Wire arc additive manufacturing (WAAM) is a direct energy deposition (DED) process with high deposition rates, but deformation and distortion can occur due to the high energy input and resulting strains. Despite great efforts, the prediction of distortion and resulting geometry in additive manufacturing processes using WAAM remains challenging. In this work, an artificial neural network (ANN) is established to predict welding distortion and geometric accuracy for multilayer WAAM structures. For demonstration purposes, the ANN creation process is presented on a smaller scale for multilayer beads on plate welds on a thin substrate sheet. Multiple concepts for the creation of ANNs and the handling of outliers are developed, implemented, and compared. Good results have been achieved by applying an enhanced ANN using deformation and geometry from the previously deposited layer. With further adaptions to this method, a prediction of additive welded structures, geometries, and shapes in defined segments is conceivable, which would enable a multitude of applications for ANNs in the WAAM-Process, especially for applications closer to industrial use cases. It would be feasible to use them as preparatory measures for multi-segmented structures as well as an application during the welding process to continuously adapt parameters for a higher resulting component quality.

Development of Bead Modelling for Distortion Analysis Induced by Wire Arc Additive Manufacturing using FEM and Experiment

In this research, Wire Arc Additive Manufacturing is modelled and simulated to determine the most suitable bead modelling strategy. This analysis is aimed to predict distortion by means of thermomechanical Finite Element Method (FEM). The product model with wire as feedstock on plate as substrate and process simulation are designed in form of multi-layered beads and single string using MSC Marc/Mentat. This research begins with finding suitable WAAM parameters which takes into account the bead quality. This is done by using robotic welding system with 01.2mm filler wire (AWS A5.28 : ER80SNi1), shielding gas (80% Ar/ 20% CO2) and 6mm-thick low carbon steel as base plate. Further, modelling as well as simulation are to be conducted with regards to bead spreading of each layers. Two different geometrical modelling regarding the weld bead are modelled which are arc and rectangular shape. Equivalent material properties from database and previous researches are implemented into simulation to ensure a realistic resemblance. It is shown that bead modelling with rectangular shape exhibits faster computational time with less error percentage on distortion result compared to arc shape. Moreover, by using the rectangular shape, the element and meshing are much easier to be designed rather than arc shape bead.

A randomized placebo-controlled double-blind study evaluating the time course of response to methylphenidate hydrochloride extended-release capsules in children with attention-deficit/hyperactivity disorder.

The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extended-release multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting. This randomized double-blind placebo-controlled study included children 6-12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period (≤4 weeks) and a 2 day medication washout period; 2) open-label period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2-4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0-12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance. The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p=0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0-12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo (p≤0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study. MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6-12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose. ClinicalTrials.gov Identifier: NCT01269463.

Steady-state bioavailability of extended-release methylphenidate (MPH-MLR) capsule vs. immediate-release methylphenidate tablets in healthy adult volunteers.

The objective of the study was to determine the relative bioavailability of an extended-release multilayer bead formulation of methylphenidate hydrochloride (MPH-MLR) 80mg vs. methylphenidate immediate-release (IR; Ritalin(®)) tablets as single and multiple doses in the fed state. A single-center, multiple-dose, randomized, open-label, two-period crossover study conducted in 26 healthy adults assigned to 4days of once-daily MPH-MLR 80mg or IR methylphenidate 25mg three times daily. MPH-MLR 80mg produced reproducible biphasic profiles of plasma methylphenidate concentrations characterized by a rapid initial peak, followed by a moderate decline reaching a plateau ~5 h post dose, then a gradual increase culminating in an attenuated second peak ~7h post dose. Maximum concentration was lower for MPH-MLR 80mg than IR methylphenidate 25mg three times daily on day 1 (23.70 vs. 31.47ng/mL); exposure was similar. The geometric mean ratios (MPH-MLR/IR methylphenidate [90% CI]) of log-transformed area under the plasma drug concentration-time curve to the last measurable observation (day 1: 0.88 [84.75-91.80]; day 4: 0.84 [81.16-86.94]), and area under the plasma drug concentration extrapolated to infinity (day 1: 0.93 [88.57-97.28]; day 4: 0.88 [84.48-91.17]) were within the 80-125% bioequivalence range. The mean±SD MPH-MLR 80-mg capsule day 4 area under the plasma drug concentration vs. time curve from 0 to 4h (74.5±15.2ng·h/mL) was greater than IR methylphenidate 25mg three times daily (66.0±17.4ng·h/mL), confirming steady-state levels during the study period. All treatment regimens were safe and well tolerated. MPH-MLR 80-mg capsule once daily or IR methylphenidate 25mg three times daily provides comparable maximum methylphenidate concentrations and systemic exposure in the fed state.

Preparation and <i>In Vitro</i> Release of Alginate/Chitosan Microparticles Containing α-Glucosidase Inhibiting Peptide

Alginate-chitosan multilayer beads containing α-glucosidase inhibiting peptide (GIP) from Ruditapes philippinarum were prepared to develop stable, non-toxic microcapsules. The optimal conditions were alginate concentration (w/v) 1.0%, alginate/GIP ratio (w/w) 1:5, calcium chloride concentration (w/v) 5% and chitosan concentration (w/v) 2.0%, which were obtained through single factor tests and orthogonal experiments. Under the conditions, the encapsulation efficiency (EE%) was 67.21% and the drug-loading percentage was 33.67%.According to the release study, the release rate of GIP was lower than 30% after incubation in simulated gastric fluid (SGF) for 3h and the rate was higher than 70% after incubation in simulated intestinal fluid (SIF) for 5h. The inhibiting rate was 25.13% after treatment in SIF when the concentration of GIP was 10mg/mL. Accordingly,the microcapsules prepared in this paper are acid resistant and therefore can be given orally.

Characterization of deposited layer fabricated by direct laser melting process

Deposition dimensions are important in the final applications of products made by direct laser melting (DLM). This investigation used a 200 W fiber laser to produce single-line beads from stainless steel 316L powder using a variety of different energy distributions. To investigate the deposited layer, deposition width, height, penetration depth, and side surface roughness were measured. In order to validate the effectiveness of the two main process parameters (laser power and scan rate), multi-layered beads were fabricated by the sequential layering of single lines. It was found that with an increase in linear energy density, the wetting angle was reduced, and the average roughness was also increased with linear energy density. An equation that predicts the deposition height for a multi-layered bead is proposed and experimentally validated in this study. For deposited layer applications, the material properties of the deposited layer, such as contact angle, interfacial contact resistance, and flexural strength are estimated. The rougher deposited layers show higher contact angle and interfacial contact resistance. The flexural strength of the DLM fabricated specimen is above 250 MPa.

Alternate Polyelectrolyte Coating of Chitosan Beads for Extending Drug Release

In the present study, we addressed the factors modifying ciprofloxacin release from multiple coated beads. Beads were prepared by simple ionic cross-linking with sodium tripolyphoshate and coated with alginate and/or chitosan to prepare single, double, or multilayered beads. The water uptake capacity depended on the nature of beads (coated or uncoated) and pH of test medium. The number of coatings given to the beads influenced ciprofloxacin release rate. The coating significantly decreased the drug release from the beads in comparison to uncoated beads (p < 0.001). When the beads were given three coatings, viz., alginate, chitosan, and again alginate, the drug release appeared to follow the pattern exhibited by colon-targeted drug delivery systems with time dependent release behavior. The increase in coating formed a barrier for easy ingress of dissolution medium into the bead matrix, reducing the diffusion of drug.

Analysis of Residual Stresses in Multi-Pass Welding Using Element Generation Technique

A finite element procedure to predict residual stresses on the multi-pass arc welding considering the multi-layered beads and solid–liquid phase transformation in the melted bead is implemented and experimentally validated. The nonlinearities of material properties are considered in the thermo-elasto-plastic distortion analysis. Element birth and death technique is used to simulate the weld metal added to base metal in both heat transfer and thermo-elasto-plastic analysis. Residual stresses and strains are computed for butt welding and T-joints fillet welding. The stress distributions calculated by proposed finite element analysis procedure are compared with the measured values of experiments and data available in the other studies. The efficiency of the proposed finite element analysis and experimental procedure is discussed and demonstrated.

Investigation of water uptake behavior and stability of calcium alginate/chitosan bi-polymeric beads: Part-1

This study describes a detailed investigation of swelling and degradation behavior of ionically cross-linked sodium alginate/chitosan bi-polymeric beads in the environment of varying pH to mimic transition of oral dosage form from mouth to colon. The bead sample S 1, prepared by complex coacervation was found to be stable for nearly 320 ± 12 min in the media of varying pH. The variation in amount of chitosan or cross-linking with Al 3+ ions did not result in any enhancement in their stability. However, using 6% sodium alginate solution the beads could be stabilized for nearly 10 h. The formation of multilayer beads (S 2, S 3 and S 4) resulted in an drastic increase in the stability of beads. The mechanism of water uptake, as studied for the sample S 1 indicated ion exchange process between Ca 2+ ions present in polyguluronate and polymannuronate blocks of alginate and Na + ions present in phosphate buffer medium. This was further confirmed by linear nature of plot obtained between fractional water uptake and time 1/2.

Chitosan–alginate multilayer beads for controlled release of ampicillin

The aim of this study is to develop multilayer beads with improved properties for controlled delivery of the antibiotic ampicillin. Ionotropic gelation was applied to prepare single and multilayer beads using various combinations of chitosan and Ca 2+ as cationic components and alginate and polyphosphate as anions. Beads prepared with higher concentrations of chitosan entrapped more ampicillin. During incubation in simulated gastric fluid, the beads swelled and started to float but did not show any sign of erosion. Single layer chitosan–alginate beads released 70% of the drug within 4 h. Multilayer beads released only 20–30% in the same period of time. During subsequent incubation in simulated intestinal fluid, both single and multilayer beads continued to release drug. At least part of this release is due to disintegration of the beads. The rate of release both in gastric and intestinal fluid and the kinetics of disintegration in intestinal fluid can be controlled by changing the chitosan concentration in the coagulation fluid. The release of the drug can also be controlled by the degree of cross-linking using polyphosphate. Cross-linked multilayer beads were prepared that released only 40% of the entrapped drug during 24 h. It is concluded that chitosan–alginate multilayer beads, cross-linked with polyphosphate offer an opportunity for controlled gastrointestinal passage of compounds with low molecular weight like ampicillin.

Chitosan-Alginate Multilayer Beads for Gastric Passage and Controlled Intestinal Release of Protein

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80–90% of the model protein within 12 h while multilayer beads released only 40–50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.

接合 ＫＶ粉末を用いたＰＰＷ肉盛溶接金属の特性

The recent deregulation allows the operators to extend the shutdown maintenance interval from the conventional one year to the maximal 4 years at their petrochemical plants, where the components should withstand the hostile service conditions, high temperature and pressure, and severe erosion and corrosion, more than before. Consequently it gets a crucial technical challenge to achieve greater durability of the components. Plasma Powder Welding (PPW) is an established overlaying process to yield the unrivaled erosion-corrosion resistance. As filler alloy powders for PPW, authors designed Co-Cr-Mo-V system DAPKV series bearing 1 to 4%C and 5 to 17%V, which disperse fine spherical VC carbides in the overlay. Even with higher C contents, they are ready to weld into the multi-layered beads up to 18mm in height, free from cracking without pre-heating. They develop the neat overlays with the RT-800°C hardness and the abrasion and wear resistance both higher than the conventional Co-Cr-W system Stellite series. Most of their mechanical properties are superior to Stellites'. Some components overlaid with KV10, 2%C and 9%V, proves their multiplied service lives at refineries and plastic injection shops.

Quantification of the toughness distribution in a heavy section submerged arc multilayer reactor pressure vessel weldment

In a working procedure qualification test weld representing a heavy section circumferential reactor pressure vessel (RPV) weld tested in 1968, lower toughness values were observed in the top layer region compared to those found in the filler region. Gleeble simulation, extensive microscopic evaluation, diligent Charpy V-notch testing and modelling of the bead sequence and distribution of alloying elements was applied to explain this effect. It could be revealed that the microstructure of the weld metal is the most important factor influencing the toughness. When an ‘as welded’ microstructure is partly or fully reaustenitised by the adjacent multilayer beads, the microstructure transforms and the toughness increases. In the filler region, 85% of the cross-section consists from transformed microstructure, whereas in the top layer only 20% are transformed. It is quite evident that, accidentally, the notch tip of Charpy samples in 1968 were placed in untransformed microstructures. When the top layer on the inner surface of the RPV is weld cladded by austenitic stainless steel, full transformation occurs and the toughness representing the filler region can be taken into account for safety evaluations.

Bead Compacts. I. Effect of Compression on Maintenance of Polymer Coat Integrity in Multilayered Bead Formulations

Little information is available on the comparability of beads for oral sustained-release dosage forms. It is known that polymer-coated beads may fuse together to produce a non-disintegrating controlled-release matrix tablet when compressed. This study evaluates the effect of compression on beads with multiple layers of polymer and drug coat, and the effect of cushioning excipients and compaction pressure on drug release from compressed bead formulations. The multilayered beads consist of several alternating layers of acetaminophen (APAP) and polymer coats (Aquacoat®) with an outer layer of mannitol as a cushioning excipient. Percent drug release versus time profiles showed that the release of drug decreases from noncompacted beads as the amount and number of coatings increases, with only 43% of drug released in 24 hr for coated beads with 10 layers. It was shown that the compacted multilayered beads will disintegrate in gastrointestinal fluids, providing a useful drug release pattern. It was shown that beads of drug prepared by any method can be spray-layered with excipients such as Avicel and mannitol. Spray-layering of the cushioning excipient onto beads can provide an effective way to circumvent segregation issues associated with mixing of the polymer-coated beads and powdered or spherical/nonspherical cushioning excipients. Spray layering of the cushioning excipient can also provide excellent flow properties of the final formulation as visually observed in our experiments. Triple-layered caplets (TLC) were also prepared with outer layers of Avicel PH-101 or polyethylene oxide (PEO), and a center layer of polymer-coated beads. For TLC, the polymer coating on the beads fractured, and nondisintegrating matrix formulations were obtained with both caplet formulations.