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Hydrogen absorbing materials, such as metal hydrides, present a possible solution for hydrogen storage. During the absorption process these materials swell, which can put the mechanical integrity of its container at risk. One possibility is to increase the flowability of the absorbing material, usually a fine cohesive powder, so that it can rearrange within its container during the swelling stage. In this work, we study if this rearrangement could be improved by the addition of Aerosil, a type of colloidal silica widely used as glidant agent. The walls of a stainless steel reactor are instrumented with strain gauges to measure the accumulation of stresses due to hydrogen absorption-desorption cycles. We explore the container filled with pure LaNi5 absorbing material previously activated, so as with different Aerosil-added proportions. Results show that Aerosil allows avoiding stress build-up, for all glidant concentrations used in present study.

The aim of this study was to compare the bulk lactose flow behavior with a defined fraction with smaller particles obtained by sieving from the bulk lactose and to evaluate the effect of a glidant addition on both samples. These powders showed, in a previous work, similar flow indexes (ffc) that motivated the addition of colloidal silicon dioxide in order to observe if there were any changes in their flow behaviors. To evaluate this effect on the diluent flow behavior, the methods described in the European Pharmacopeia were used. The results obtained from conventional methods and shear cell methods (using the Powder Flow Tester) were compared, and they showed evident differences in the bulk and tapped densities values and flow classifications. The lactose monohydrate (FTotal) and lactose with particles smaller than 63 μm (F

The aim of the present research is to develop and optimize Eperisone Hydrochloride extended release matrix tablets. Eperisone Hydrochloride is an antispasmodic drug mainly used to relieve pains it acts by relaxing the skeletal and smooth vascular muscles by blocking spinal reflexes drug which has oral bioavailability of 70% due to hepatic metabolism. Sustained release matrix tablets of Eperisone Hydrochloride were prepared through wet granulation technique by using HPMC K4M and EC as polymers, PVPK30 as binder, Magnesium stearate as lubricant and Talc as glidant. The granules of different formulations were determined for pre compression parameters. The prepared granules along with the excipients were then compressed. The formulated tablets were evaluated for physical characteristics viz. Hardness, Thickness, % Weight variation, Friability and the drug content. Furthermore the tablets evaluated for the in vitro release studies. Out of all the 8 formulations F7 showed desired characteristics in the physical parameters and in vitro drug release of 85.48% in 12hrs.The F7 dissolution data was best fitted to the Zero order model. The prepared Eperisone Hydrochloride matrix tablets found to be having a potential extended drug release.

The aim of this study was to compare the bulk lactose flow behavior with a defined fraction with smaller particles obtained by sieving from the bulk lactose and to evaluate the effect of a glidant addition on both samples. These powders showed, in a previous work, similar flow indexes (ffc) that motivated the addition of colloidal silicon dioxide in order to observe if there were any changes in their flow behaviors. Methods To evaluate this effect on the diluent flow behavior, the methods described in the European Pharmacopeia were used. Results The results obtained from conventional methods and shear cell methods (using the Powder Flow Tester) were compared, and they showed evident differences in the bulk and tapped densities values and flow classifications. The lactose monohydrate (FTotal) and lactose with particles smaller than 63 μm (F, The authors would like to thank Dra. Teresa Malta and Atral, S.A., for the kindly supplying of the lactose monohydrate, that made this work possible. This work was supported by the Applied Molecular Biosciences Unit-UCIBIO, which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019).

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression., Graphical abstract Unlabelled Image, Highlights • ASD technology has influence on particle morphology • Compression behavior dominated by particle morphology • Vacuum drum dried intermediate direct compressible into tablets • Vacuum drum dried material shows better tabletability as milled extrudate • ASD technology: no impact on tablet disintegration/dissolution

The objective of this work was to analyze the flow behavior of a commonly used filler (pregelatinised starch) and the effect of two of the most used lubricants (talc and colloidal silicon dioxide). The studies were carried out according to the conventional methods (Angle of Repose, Bulk and Tapped densities and from these the Compressibility Index) and shear cell methods (Brookfield Powder Flow Tester apparatus) described in European Pharmacopeia (Ph. Eur.). The results showed some surprising and unexpected values for the flow behavior of this filler under influence of the methods and the used glidants. Regarding pure starch and mixtures containing talc, the flow behavior was similar between them and the Flow Index (ffc) values varied between 1.8 and 4 (very cohesive and cohesive) as consolidation stress (σ1) increased. In this case, the glidant effect was not observed. However, for the mixtures of starch with colloidal silicon dioxide this effect was observed providing Flow Index (ffc) values between 2.6 and 8.9 (cohesive and easy-flowing) as consolidation stress (σ1) increased. Other parameters that are also used to characterize flow properties, more specifically, within silos, chutes and hoppers, such as effective angle of internal friction (φe), effective angle of wall friction (φx), critical arching and critical rathole values, provided similar information. Based in the obtained results from all tests it can be said that the talc did not induce improvement on the starch flow behavior in the used conditions in opposition to the effect produced by colloidal silicon dioxide.HighlightsExample 1. A good flowability of powders is needed in order to be compressed/filled;Example 2. The overcome the poor flow it is usual to use glidants;Example 3. CSD improved the pregelatinised starch (Starch 1500®) flow;Example 4. Talc do not have relevant effect in the pregelatinised starch (Starch 1500®) flow;Example 5. Powder FlowTester method showed more complete and consistent results.

Dysphagia refers to difficulty swallowing certain foods, liquids, or pills. It is common among the elderly with chronic diseases who need to take drugs for long periods. Therefore, dysphagia might reduce compliance with oral drug administration in the aging population. Many pharmaceutical companies search for new products to serve as swallowing aids. Existing products are expensive and do not suit all geriatric patients. Therefore, this study aimed to develop and investigate pill swallowing aid gels prepared from carboxymethyl cellulose and chitosan. We formulated gels by dissolving different concentrations of carboxymethyl cellulose and low or high molecular weight chitosan in solvents to find appropriate gel rheology properties. We then added several portions of glycerin as the glidant of the formulation. We found that the optimized gel formulation was 6.25% (w/w) chitosan with a molecular weight of 80–120 kDa dissolved in 1.2% acetic acid and 4% (w/w) glycerin. The developed pill swallowing gel’s rheology was pseudoplastic with a viscosity of 73.74 ± 3.20 Pa⸱s. The developed chitosan gel had enhanced flow ability, it allowed the pill to cross a 300 mm tube within 6 s, while the reference product took 3 s. Even though the reference product could carry the pill in the tube faster, the chitosan gel better covered the pill, making it more convenient to use. Finally, using a theophylline tablet as a model tablet dosage form, we assessed the gel’s effect on drug disintegration and dissolution. The chitosan gel delayed the tablet disintegration time by about 3–7 min and slightly affected the theophylline dissolution rate. Lastly, all gels were physically stable after a month of storage in the stress condition. These results show the feasibility of manufacturing a chitosan gel usable as a pill swallowing gel for patients with dysphagia.

The article is devoted to the results of the theoretical and experimental investigations on the development of the optimal formulation of the pharmaceutical composition based on Kathiazin and Succinic acid in the solid gelatinous capsules. The glutaminic acid has been introduced into the pharmaceutical composition to improve the bioavailability of the succinic acid. The content of active pharmaceutical substances has been determined. The single dose of Kathiazin is 120 mg, succinic and glutaminic acids — 100 mg. The kind of auxiliary substances used in modern pharmaceutical technology of the solid dosage forms has been grounded according to the literature data. The pharmacotechnological testing of the active pharmaceutical ingredients and auxiliary substances used in our research work has been carried out. The pharmaco-technological properties of the substances investigated according to the articles of State Pharmacopoeia of Ukraine (2 edition) have been estimated. The assessment of obtained data allowed to elaborate the composition of the experimental capsules masses. The flowability, bulk density, angle of repose, compressibility index and Hausner ratio of the mixtures created have been investigated due to requirements of the State Pharmacopoeia of Ukraine. On the base of scientific researching the most perspective pharmaceutical composition with excellent values of the flowability, angle of repose, bulk density, compressibility index and Hausner ratio has been chosen. This composition contains mannitol as the basic excipients for capsules mass. The silicon dioxide colloidal (Aerosil®) is considered to be glidant substance which provides excellent flowability. As the result of the pharmaco-technological researches the qualitative and quantitative composition of the combined capsules based on Kathiazin and succinic acid has been developed. The testing of the pharmaco-technological parameters has proved the composition obtained is suitable to be encapsulated using different types of laboratory and industrial equipment. The elaborated combined dosage form based on Kathiazin and succinic acid may be proposed as a new original medicine with pleiotropic activity for treatment hepatitis of different origin in men with spermatogenesis disturbances.

3D powder printing (3DPP) attracts much attention in the field of construction and decoration. However, the strong hygroscopicity and high tendency to agglomerate of gypsum powder give rise to a poor flowability, which is crucial during large-size 3DPP procedure. This study aims to compare gliding effect of silica particles with different sizes, shapes and surface properties on poor-flow gypsum powder. Angle of repose (AOR), flow rate of the modified powders and surface morphology of the modified particles were evaluated. The results showed that silica particles of different hydrophobicity presented various extent of glidant effect. For hydrophobic nanosilica, an optimum content (1.0 wt% in this study) could best minimize AOR of the modified powder, leading to more smooth and voidless powder bed of gypsum powder than unmodified gypsum powder. The research found an optimum glidant which could improve the flowability of gypsum powder, resulting in good quality during 3DPP procedure.

Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e., blend) existing of a highly dosed very poorly flowing active pharmaceutical ingredient (API) leading to insufficient feeding capacity was investigated. Furthermore, the API showed very high batch-to-batch variability in raw material properties dominating the formulation blend properties. Formulation changes were evaluated to improve the flowability of the blends and to mitigate the impact of API batch-to-batch variability on the twin-screw feeding. Herewith, feeding evaluation tests and an extensive material characterization of the reformulated blends were performed to assess the impact of the formulation changes upon continuous twin-screw feeding. The transfer of the glidant from extra-granular to intra-granular phase allowed to improve the flowability of the blends. A sufficient feeding capacity for the downstream process and a mitigation of the impact of batch-to-batch variability of the API upon twin-screw feeding of the blends could be achieved. No effect of the formulation or of the API properties on the feeding stability was observed. The material characterization of the blends allowed identifying the material attributes which were critical for continuous twin-screw feeding (i.e., bulk density, mass charge and powder cohesiveness).

The increasing interest in the use of nanoparticles for biomedical applications has resulted in a growing demand for efficient and scalable methods that enable their preparation with fine control over particle size, distribution and morphology. In this work we report a novel flow-based method for the flash nanoprecipitation of size-controlled D-leucine nanoparticles for spray-drying formulations. Preliminary experiments were conducted in batch to define the best flowable conditions that were then optimized considering the nanoparticle size and distribution using a mesofluidic flow system. The method was applied to the streamlined preparation of D-leucine nanoparticles readily nebulized using mini and nanospray-dryer devices and characterized by SEM analysis. Finally, the D-leucine atomized powder was used as a glidant in dry powder for inhalation with micronized budesonide, a poorly water-soluble and low flowable anti-asthma drug.

This study examined the selection of small amounts of excipients capable of improving the compactability of ibuprofen, thereby enabling the miniaturization of ibuprofen tablets. Various glidants in amounts of 1% of the total volume were added to dry surface-modified ibuprofen, and the tensile strengths of the resulting tablets were evaluated. The characteristics of the excipients that affected the tensile strengths of the tablets were then extracted using a tensile strength prediction model. We confirmed that the effective angle of the internal friction of the mixed powder, the coating form of the glidant, the packing fraction of the raw material, and the mixed powder affect the tensile strength of the tablet. A smooth particle layer was formed on the surface of the ibuprofen particles when a glidant with a packing fraction of

In the pharmaceutical industry, silicates are commonly used excipients with different application possibilities. They are especially utilized as glidants in low concentrations, but they can be used in high concentrations as porous carriers and coating materials in oral solid drug delivery systems. The desirable formulations of such systems must exhibit good powder flow but also good compactibility, which brings opposing requirements on inter-particle interactions. Since magnesium aluminometasilicates (MAS) are known for their interesting flow behavior reported as “negative cohesivity” yet they can be used as binders for tablet compression, the objective of this experimental study was to investigate their particle interactions within a broad range of mechanical stress from several kPa to hundreds of MPa. Magnesium aluminometasilicate (Neusilin® US2 and Neusilin® S2)-microcrystalline cellulose (Avicel® PH102) physical powder mixtures with varying silicate concentrations were prepared and examined during their exposure to different pressures using powder rheology and compaction analysis. The results revealed that MAS particles retain their repulsive character and small contact surface area under normal conditions. If threshold pressure is applied, the destruction of MAS particles and formation of new surfaces leading to particle interactions are observed. The ability of MAS particles to form interactions intensifies with increasing pressure and their amount in a mixture. This “function switching” makes MAS suitable for use as multifunctional excipients since they can act as a glidant or a binder depending on the applied pressure.

A tablet is composed of different excipients and drug. All excipients have different properties with applications. Excipients are used to provide bulk and help to bind API into a dosage form, excipient should be inert in nature with respectable physical properties. Because the physical properties play a very important role during tablet compaction. However, maximum individual excipients do not have enough physical properties especially flowability. To fulfil these requirements co-processed excipient have been starting to use in formulation industries to make tablet and capsules. All co-processes excipients have superior flowability and other physical properties and now co-processed excipients have made their own place in pharma industries. BARETab® Nutra is also a co-processed excipient, but it is a ready to use premix for direct compressible tablet and contains four different excipients like binder, glidant, disintegrant and lubricant .This study is aimed at making herbal extracts, vitamins and non-essential amino acids tablet, using BARETab® Nutra by direct compression method and evaluate in-vitro parameters like hardness, friability, disintegration time and drug released profile. Ready to use premix BARETab® Nutra delivers good tableting parameters in herbal tablet Glucosamine, vitamin tablet Pyridoxine hydrochloride and non-essential amino acid Cysteine tablet like as higher tablet hardness, less friability, less disintegration time and uniform tablet weight. All tablets carried equal amount of drug which is proved by dissolution test.

Talc is extensively used in a wide vaFiety of cosmetic products , particularly in powder products . Talc keeps the skin feeling smooth and dry. Talc in the pharmaceutical industry is used as a glidant and lubricant. Glidants such as talc improve flow properties of powder by decreasing interparticulate friction, by decreasing van der Waals forces and electrostatic charges, by changing particle size distribution, and by decreasing the effect of humidity on surfaces of host particles by forming a mechanical barrier. The loosely bound lattice layers slide over each other and form roller structures which explains its lubr ication characteristics. Talc has less deleterious effect compared to magnesium stearate on tablet in vitro properties. Talcs from different size grades were evaluated for their use in direct compression tablet formulations. Lubricant efficiencies of talcs were measured using ejection force values. The Supra grade of the Cyprus Industrial Mineral company talc was found to be most efficient of the grades tested as lubricant and also gave tablets of more acceptable in vitro properties than t ablets lubricated with magnesium stearate only. Additionally talcs in substantial percentages were evaluated for their potential as a direct compression matrix material. With commonly used excipients such as microcrystalline cellulose and lactose, the formulations were self lubricating and the tablets ejected easily. Tablets with very low friability, high crushing strength, rapid dissolution rates, good weight uniformity, content uniformity and potency of drugs were obtained. At similar compression forces, tablet hardness with the 300 grade of Alabama, Altalc, and Beaverwhite talcs was significantly greater than corresponding 400 and 500 grades. An optimum direct compression tablet formulation of a conventional theophylline tablet was achieved using the technique of response surface methodology and successive quadratic programming (SQP) . The response surfaces were obtained from a second order uniform precision hexagonal design. The tablet formulation was optimized for mean 1.n vitro dissolution time using friability, hardness, ejection force and disintegration time as constraints within the experimental region by the SQP algorithm. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis of optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values due to its inherent variation. Although pharmaceutical scientists have previously reported optimization studies, the approach used in this thesis has signifi cant advantages and has not apparently been previously used for the optimization of pharmaceutical formulation. A completely novel use for talc as a major matrix component in direct compression tablet formulation, has been proposed and examined . A robust and efficient response surface experimental design and mathematical optimization technique has been evaluated for application to the pharmaceutical sciences . The computer search method has the disadvantage of frequently giving a plural solution for suitable formulations. With the classical Lagrangian method , it can become difficult to solve the resultant set of simultaneous equations especially for nonlinear problems. The SQP method is more efficient and robust compared to previously published optimization techniques including SUMT (Successive Unconstrained Minimization Technique) . The SQP method can also be used to obtain solution to the problems solved by the previously mentioned optimization methods. ACKNOWLEDGEMENTS I would like to offer my sincere gratitude to my major professor Dr. Christopher T . Rhodes for his advice , guidance and kind support . I greatly appreciate the opportunities Dr. Christopher T . Rhodes has created for me. Our association has progressively become more enjoyable and fruitfull . Dr. Christopher T . Rhodes kind support greatly helped me in finishing the dissertation in time . A special thank you for Dr. E.R. Suryanarayan, for his guidance and ready availibility for many helpful discussions. His pleasant and friendly help is greatly appreciated. I also thank Dr . Charles Woodruff, Dr. Hosein Zia, Dr. David Woodford , and Dr. G. Verma for their assistance, encouragment and guidance. I appreciate the guidance and assistance of Dr. William D. Lawing, Dr. Edward Carney, Dr. Gregory Peck on statistical analysis. I appreciate the advice and encouragement from all my friends. Also I would like to thank Nina Kajiji and the staff at academic computer center for their assistance with SAS programs. Last but not least, I would like to offer my thanks to my parents and family members for their constant support, encouragement and love .

Microcrystalline cellulose (MCC) is one of the most popular cellulose derivatives in the pharmaceutical industry. Thanks to its outstanding tabletability, MCC is generally included in direct compression (DC) tablet formulations containing poor-tabletability active pharmaceutical ingredients. Nowadays, numerous grades of MCC from various brands are accessible for pharmaceutical manufacturers, leading to variability in MCC properties. Hence, it seems to be worthy and urgent to evaluate the influences of MCC variability on tablet quality and to identify critical material attributes (CMAs) based on the idea of Quality by Control. Besides, MCC-based co-processed excipients can effectively combine the functions of the filler, binder, disintegrant, lubricant, glidant, or flavor, and thus have drawn extensive interest. In this review, we focused specifically on the recent advances and development of MCC on DC tableting, including the functions in tablet formulations, potential CMAs, and MCC-based co-possessed excipients, therefore providing a reference for further studies.

This study investigated the effect of material properties, primarily particle size and surface energy, on the effectiveness of glidants used for the purpose of flowability enhancement. Three pharmaceutical grade glidants (Aerosil 200, Aerosil R972, and Cab-O-Sil M5P) were evaluated and blended with various pharmaceutical actives as well as cohesive excipients common to capsule and tablet formulation. Flowability enhancement was characterized by the flow function coefficient (ff c ). An industry-relevant mixer (Turbula mixer) and a highly efficient and effective mixer (LabRAM vibratory mixer) were used to further understand the effect of material properties on glidant effectiveness. While concepts of inter-particle cohesion and interaction strength were applied to evaluate their usefulness in understanding and predicting flowability enhancement, theoretical expectations did not fully explain the behavior of all three glidants. However, the study suggests that the low surface energy and optimal particle size of Aerosil R972 relative to the other glidants results in lower inter-particle force and consequently better flowability. Aerosil R972 was also shown to be more effectively utilized in the Turbula mixing process particularly for larger (d50 > 40 μm) and less cohesive (ff c > 3) materials. This may be due to its lower surface energy and hydrophobic surface which allows it to disperse easily. Overall, this study provides useful insight into the material properties which influence the effectiveness of glidants used in formulation development.

Tension accumulation in container walls is a matter of concern in hydride based hydrogen storage systems. As the hydrogen absorbing material swells during hydrogen absorption it will need to flow and accommodate within its container. Failure to do so will result in the build-up of tensions and, eventually, in the failure of the container after a number of absorption-desorption cycles. There have been several ways of avoiding the build-up of mechanical stresses: having a container geometry that allows the swelling of the hydride, combining the hydride forming alloys with other materials that can handle the volume increase or the stresses, and adding solid lubricants to improve the ability of the hydride to accommodate within the container. In the present study we explore the application of nanoscaled powders normally used in the industry as glidant agents for bulk powders. In particular, we address the influence of three different types of glidants in the flowability of LaNi5 powder: Aerosil R 805, molybdenum disulfide (MoS2) and Vulcan XC72 carbon black. For this purpose, we have used a pressurized rotating drum device that allows hydrogen pressure or vacuum to test LaNi5 in hydrogen absorbed or desorbed states. The angle of repose results indicate an improvement on powder flowability when using Aerosil in concentrations of approximately 0.05 wt% or MoS2 at concentrations of approximately 0.1 wt%. These results are in agreement with models that explain the reduction of interparticle forces when using small quantities of nanoscaled particles. Vulcan XC72 showed no effectiveness as glidant. This unexpected behavior is most likely related to its tendency to become trapped in the cracks of the larger LaNi5 particles and to form relatively large aggregates. Fil: Melnichuk, Maximiliano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina Fil: Cuscueta, Diego Javier. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Silin, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina

According to the US Food and Drug Administration and the European Food Safety Authority, amorphous forms of silica and silicates are generally recognized to be safe as oral delivery ingredients in amounts up to 1500mg per day. Silica is used in the formulation of solid dosage forms, e.g. tablets, as glidant or lubricant. The synthesis of silica-based materials depends on the payload nature, drug, macromolecule or cell, and on the target release (active or passive). In the literature, most of the examples deal with the encapsulation of drugs in mesoporous silica nanoparticles. Still to date limited reports concerning the delivery of encapsulated macromolecules and cells have been reported in the field of oral delivery, despite the multiple promising examples demonstrating the compatibility of the sol-gel route with biological entities, likewise the interest of silica as an oral carrier. Silica diatoms appear as an elegant, cost-effective and promising alternative to synthetic sol-gel-based materials. This review reports the latest advances silica-based systems and discusses the potential benefits and drawbacks of using silica for oral delivery of drugs, macromolecules or cells.

In a recent study, it was demonstrated that improving flow of a model poorly flowing and poorly compactable drug substance, acetaminophen, via dry coating while using fine excipients, may promote direct compression. To validate this novel strategy, particularly for high drug-loading formulations, this study investigates the effect of microcrystalline cellulose (MCC) particle size and dry coating on powder tabletability and flowability. It was determined that blends containing fine-sized MCC (20 μm) resulted in the highest tablet tensile strength and best tabletability because it provides higher interparticle contact area compared with coarse-sized MCC. Although tabletability can be improved using fine MCC, flowability is poor but can be improved through dry coating, a process that coats glidants (nano-sized silica) onto particle surfaces. To retain the tabletability, which was adversely affected because of the presence of glidant in the blend, while simultaneously enhancing flowability via dry coating, separately blending the drug substance with glidant is shown to be the best method of processing. The combined use of fine excipients and selective dry coating offers a novel and advantageous formulation strategy in comparison with the conventional use of coarse excipients, such as Avicel PH 102, that have been designed and marketed for direct compression.

The methods used for flow characterization of a powder mass include the angle of repose (AOR), Carr index (CI), and powder flow tester (PFT). The use of nanosilica as a flow modifier (glidant) is very common in industry. This study aims to compare the glidant effect of hydrophobic and hydrophilic silica on a poorly flowable active pharmaceutical ingredient (ibuprofen) by different flow characterization techniques. Different percentages (0.5, 1.0, and 2.0 wt%) of both types of mixed silica–ibuprofen powders were evaluated by the AOR, CI, bulk density, and PFT. The flow factor, effective angle of friction, and cohesion were determined to explain the bulk powder properties. The results show that different types of silica show different levels of flow property improvement, but the techniques do not equally discriminate the differences. Hydrophobic silica results in better improvement of the flow property than hydrophilic silica, probably because of its better surface coverage of silica on the host particles. Change of the bulk density with applied pressure was significant for the different powders. This study demonstrates that combining several characterization methods provides a better understanding of bulk powder flow properties with respect to powder–process relationships than a single flow indicator.

Suspension of microparticles in an easy-to-swallow liquid is one approach to develop sustained-release formulations for children and patients with swallowing difficulties. However, to date production of sustained-release microparticles at the industrial scale has proven to be challenging. The aim of this investigation was to develop an innovative concept in coating sustained-release microparticles using industrial scalable Wurster fluidised bed to produce oral liquid suspensions. Microcrystalline cellulose cores (particle size w/w) of dry powder glidant, magnesium stearate, to the coating chamber via an external port was applied throughout the coating process. This method significantly increased coating production yield from less than 50% to up to 99% compared to conventional coating process without the dry powder glidant. Powder rheology tests showed that dry powder glidants increased the tapped density and decreased the cohesive index of coated microparticles. Reproducible microencapsulation of a highly water-soluble drug, metoprolol succinate, was achieved, yielding coated microparticles less than 200 μm in size with 20-h sustained drug release, suitable for use in liquid suspensions. The robust, scalable technology presented in this study offers an important solution to the long-standing challenges of formulating sustained-release dosage forms suitable for children and older people with swallowing difficulties.

The mucilage from Brasenia schreberi (BS) exhibits various biological activities, including antialgal, antibacterial, soluble-fiber properties, and excellent lubricating behavior. Thus, the extraction and wide use of mucilage in the food industry are crucial. In this study, the high-speed shear-assisted extraction of mucilage from BS was optimized by using response surface methodology (RSM). The optimal extraction conditions were as follows: Extraction temperature of 82 &deg, C, extraction time of 113 min, liquid&ndash, solid ratio of 47 mL/g, and shear speed of 10,000 rpm. Under these conditions, the actual yield of BS mucilage was 71.67%, which highly matched the yield (73.44%) predicted by the regression model. Then, the BS mucilage extract was powdered to prepare the capsule, and the excipients of the capsule were screened using a single-factor test to improve the disintegration property and flowability. The final capsule formulation, which consisted of: 39% BS mucilage powder (60 meshes), 50% microcrystalline cellulose (60 meshes) as the filler, both 10% sodium starch glycolate and PVPP XL-10 (3:1, 60 meshes) as the disintegrant, both 1% colloidal silicon dioxide and sodium stearyl fumarate (1:1, 100 meshes) as the glidant by weight, were used for preparing the weights of a 320 mg/grain of capsule with 154.7 &plusmn, 0.95 mg/g polysaccharide content. Overall, the optimized extraction process had a high extraction rate for BS mucilage and the capsule formulation was designed reasonably.

In industrial sectors, such as chemical, pharmaceutical or food industries, poor flowability of powders is often the causes of process malfunction. Poor flowability can lead to the blocking of powders in a silo, dosing and filling problems, or even bad quality on final product. To ensure proper process operation, it is therefore necessary and essential to evaluate the flowability of powders used. For this purpose, several experimental techniques such as angle of repose devices, shear cells or powder packing devices can be used. Flowability indices can then be defined in order to classify the powders according to the flow quality. Experimental tests have been carried out on several types of powders and the first results have shown that the transition from one technique to another can modify or even reverse the classification of the powder flowability. Indeed, according to the techniques studied, powders are subjected to different mechanical stresses and therefore the choice of the technique must be adapted to the real case of study. In this work, we were particularly interested to the evaluation of powders flowability from compaction devices. The work carried out has shown that the dynamic parameters (amplitude and frequency of taps) greatly influence the classification of powders flowability. From an energy approach, it has been shown that the evaluation of the flowability from Hausner ratio can be given by a compaction technique only if it achieves a value of energy required to obtain a maximal compaction of the particles. Finally, an implementation study of flowability evaluation techniques was carried out in the field of formulation by focusing on the quantitative evaluation of the influence of a glidant; Dans les secteurs industriels tels que l’industrie chimique, pharmaceutique ou agro-alimentaire une faible aptitude à l’écoulement des poudres est souvent à l’origine du mauvais fonctionnement d’un procédé. Une mauvaise coulabilité peut ainsi entrainer le blocage de poudres dans un silo, des problématiques de dosages et de remplissage ou encore une détérioration de la qualité du produit final. Pour assurer un bon fonctionnement du procédé, il est donc nécessaire et essentiel d’évaluer la coulabilité de poudres utilisées. Pour cela, plusieurs techniques expérimentales telles que les dispositifs de mesure d’angle, les cellules de cisaillement, les dispositifs de tassement de poudre peuvent être utilisées. Des indices de coulabilité sont alors définis permettant de classer les poudres selon la qualité de l’écoulement. Des essais expérimentaux ont été menés sur plusieurs types de poudres et les premiers résultats ont montré que le passage d’une technique d’évaluation à une autre peut modifier, voire inverser le classement de la coulabilité des poudres. En effet, selon les techniques étudiées les poudres sont soumises à des sollicitations mécaniques différentes et donc le choix de la technique doit être adapté au cas réel d’étude. Dans ce travail, nous nous sommes intéressé plus particulièrement au cas de l’évaluation de l’écoulement de poudres à partir de dispositifs de compaction. Le travail réalisé a montré que les paramètres dynamiques (amplitude et fréquence de chocs) influencent énormément le classement de la coulabilité des poudres. A partir d’une approche énergétique, il a été montré qu’une évaluation et quantification de la coulabilité à partir du rapport d’Hausner ne peut être donnée par une technique de compaction que si celle-ci permet d’atteindre une valeur d’énergie nécessaire à l’obtention d’une compaction maximale des particules. Enfin, une étude de mise en œuvre des techniques d’évaluation de la coulabilité a été réalisée dans le domaine de la formulation en s’intéressant à l’évaluation quantitative de l’influence d’un agent d’écoulement

In industrial sectors, such as chemical, pharmaceutical or food industries, poor flowability of powders is often the causes of process malfunction. Poor flowability can lead to the blocking of powders in a silo, dosing and filling problems, or even bad quality on final product. To ensure proper process operation, it is therefore necessary and essential to evaluate the flowability of powders used. For this purpose, several experimental techniques such as angle of repose devices, shear cells or powder packing devices can be used. Flowability indices can then be defined in order to classify the powders according to the flow quality. Experimental tests have been carried out on several types of powders and the first results have shown that the transition from one technique to another can modify or even reverse the classification of the powder flowability. Indeed, according to the techniques studied, powders are subjected to different mechanical stresses and therefore the choice of the technique must be adapted to the real case of study. In this work, we were particularly interested to the evaluation of powders flowability from compaction devices. The work carried out has shown that the dynamic parameters (amplitude and frequency of taps) greatly influence the classification of powders flowability. From an energy approach, it has been shown that the evaluation of the flowability from Hausner ratio can be given by a compaction technique only if it achieves a value of energy required to obtain a maximal compaction of the particles. Finally, an implementation study of flowability evaluation techniques was carried out in the field of formulation by focusing on the quantitative evaluation of the influence of a glidant, Dans les secteurs industriels tels que l’industrie chimique, pharmaceutique ou agro-alimentaire une faible aptitude à l’écoulement des poudres est souvent à l’origine du mauvais fonctionnement d’un procédé. Une mauvaise coulabilité peut ainsi entrainer le blocage de poudres dans un silo, des problématiques de dosages et de remplissage ou encore une détérioration de la qualité du produit final. Pour assurer un bon fonctionnement du procédé, il est donc nécessaire et essentiel d’évaluer la coulabilité de poudres utilisées. Pour cela, plusieurs techniques expérimentales telles que les dispositifs de mesure d’angle, les cellules de cisaillement, les dispositifs de tassement de poudre peuvent être utilisées. Des indices de coulabilité sont alors définis permettant de classer les poudres selon la qualité de l’écoulement. Des essais expérimentaux ont été menés sur plusieurs types de poudres et les premiers résultats ont montré que le passage d’une technique d’évaluation à une autre peut modifier, voire inverser le classement de la coulabilité des poudres. En effet, selon les techniques étudiées les poudres sont soumises à des sollicitations mécaniques différentes et donc le choix de la technique doit être adapté au cas réel d’étude. Dans ce travail, nous nous sommes intéressé plus particulièrement au cas de l’évaluation de l’écoulement de poudres à partir de dispositifs de compaction. Le travail réalisé a montré que les paramètres dynamiques (amplitude et fréquence de chocs) influencent énormément le classement de la coulabilité des poudres. A partir d’une approche énergétique, il a été montré qu’une évaluation et quantification de la coulabilité à partir du rapport d’Hausner ne peut être donnée par une technique de compaction que si celle-ci permet d’atteindre une valeur d’énergie nécessaire à l’obtention d’une compaction maximale des particules. Enfin, une étude de mise en œuvre des techniques d’évaluation de la coulabilité a été réalisée dans le domaine de la formulation en s’intéressant à l’évaluation quantitative de l’influence d’un agent d’écoulement

The work was aimed at evaluating the efficiency of multifunctional magnesium aluminosilicate materials (MAS) as a novel glidant in solid dosage forms. MAS are known for their very low cohesive interactions and their utilization could avoid the disadvantages associated with conventional glidant usage. Flow properties of several mixtures comprising a model excipient (microcrystalline cellulose) and a glidant were characterized using a powder rheometer FT4. The mixtures were formulated to represent effects of glidant types, various levels of glidant loading, particle size and mixing time on flow properties of the model excipient. Pre-conditioning, shear testing, compressibility, flow energy measurements and an additional tapping test were carried out to monitor flow properties. Mixtures were analyzed employing scanning electron microscopy, using a detector of back-scattered electrons to identify a mechanism of MAS towards improving the mixture flow properties. All studied parameters were found to have substantial effects on mixture flow properties, but the effect of mixing time was much less important compared to mixtures based on traditional glidant. The mechanism of MAS glidant action was found to be different compared to that of traditional one, having less process sensitivity, so that MAS utilization as glidant could be advantageous for the formulation performance.

In pharmaceutical industry, the use of lubricants is mostly based on historical experiences or trial and error methods even these days. It may be demanding in terms of the material consumption and may result in sub-optimal drug composition. Powder rheology enables more accurate monitoring of the flow properties and because the measurements need only a small sample it is perfectly suitable for the rare or expensive substances. In this work, rheological properties of four common excipients (pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium and magnesium stearate) were studied by the FT4 Powder Rheometer, which was used for measuring the compressibility index by a piston and flow properties of the powders by a rotational shear cell. After an initial set of measurements, two excipients (pregelatinized maize starch and microcrystalline cellulose) were chosen and mixed, in varying amounts, with anhydrous colloidal silicon dioxide (Aerosil 200) used as a glidant. The bulk (conditioned and compressed densities, compressibility index), dynamic (basic flowability energy) and shear (friction coefficient, flow factor) properties were determined to find an optimum ratio of the glidant. Simultaneously, the particle size data were obtained using a low-angle laser light scattering (LALLS) system and scanning electron microscopy was performed in order to examine the relationship between the rheological properties and the inner structure of the materials. The optimum of flowability for the mixture composition was found, to correspond to empirical findings known from general literature. In addition the mechanism of colloidal silicone dioxide action to improve flowability was suggested and the hypothesis was confirmed by independent test. New findings represent a progress towards future application of determining the optimum concentration of glidant from the basic characteristics of the powder in the pharmaceutical research and development.

O Projeto Farmácia Viva é o primeiro projeto de assistência social farmacêutica desenvolvido no Brasil baseado no emprego científico de plantas medicinais. Dentre as formulações padronizadas a partir de cápsulas gelatinosas duras, destacam-se as cápsulas contendo Extrato Seco de Valeriana. Para manipulação dessas cápsulas, é necessária uma quantidade adicional de excipientes, que possuem papel importante na qualidade, segurança e no desempenho do medicamento. O objetivo deste estudo é padronizar excipientes para formulação fitoterápica em cápsulas manipuladas no Projeto Farmácia Viva. A metodologia seguida foi por meio de análise bibliográfica sobre os variados excipientes e fitoterápicos e análise de bulas de medicamentos para posterior sugestão de padronização. Foram manipuladas 30 cápsulas e submetidas ao controle da qualidade, onde foram avaliados o peso médio, limite de variação, coeficiente de variação, desvio padrão e variação do conteúdo teórico das cápsulas. A formulação de Valeriana proposta teve como excipientes escolhidos o estearato de magnésio (0,5 %) como lubrificante, o dióxido de silício coloidal (1,0 %) como deslizante, o talco farmacêutico (1,0 %) como adsorvente, o amido farmacêutico (73,0 %) como um diluente hidrofóbico, lactose monohidratada (24,5 %) como um diluente hidrofílico. Todos os resultados do controle da qualidade obtidos atenderam as especificações farmacopeicas.

This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

In this study, we examined the characteristics of glidant that affect the improvement of the flowability of APIs by using the dry surface modification of ibuprofen. In addition, the screening method of glidant suitable for improving flowability of APIs was examined. As a result of evaluation of mixed powder with surface modification using various inorganic fine particles with different physical properties, it became clear that the packing fraction had the most influence regardless of the component. This was thought to able to coat the surface with small quantities because the smaller the packing fraction, the more it was able to dispersed from the less contacts between the glidant particles. The packing fraction of glidant was correlated with the (SE/CBD)-1 which was calculated value from the results measured with powder rheometer. From this results, when using any excipient as a glidant for dry surface modification, it is now possible to estimate the effect of improving flowability simply by measuring with a powder rheometer. Based on this study, it is possible to select excipients suitable for improving APIs flowability and to estimate the improvement effect, and therefore, it is expected to improve the efficiency of prescription design work.

Cold is a global common infectious disease accompanied by symptoms such as headache and stuffy nose. Ibuprofen (IBU) and phenylephrine hydrochloride (PE) were commonly used for common cold due to their different effects in relieving fever and the main symptoms such as nasal congestion and high sinus pressure. However, the commercial tablets of IBU and PE have to be administered 2 to 3 times per day due to their short half-life, with inconvenience for patient and fluctuations of plasma concentration. Bilayer tablet technology was utilized to design the IBU-PE sustained release tablets because of the significantly different solubility of IBU and PE in release media. The formulations of IBU layer and PE layer contain different viscosity grades of hydroxypropyl methylcellulose (HPMC) as sustained-release matrix, hydrophilic diluent, and traditional glidant and lubricant. The sustained release bilayer tablet exhibited satisfying sustained release performance with the mechanisms of diffusion and matrix erosion. Compared with the conventional tablets, the IBU-PE sustained release bilayer tablet expressed significantly sustained-release behavior with decreased Cmax and prolonged Tmax in fasted conditions for IBU and PE. Though IBU of IBU-PE sustained release bilayer tablet was bioequivalent to the commercial IBU tablet, the relative bioavailability of PE from the bilayer tablets was 87.49 ± 20.00% (90% confidence interval was 72.3 to 102.5%), indicating bioinequivalence probably due to the “first pass” effect.

In this study, polyvinylpyrrolidone (PVP) was spray dried with l -leucine (PVP-Leu) to create a prototype multifunctional interactive excipient. The physico-chemical and bulk properties such as particle size, surface composition, surface energy and bulk cohesion of PVP-Leu was measured and compared against pure spray dried PVP (PVP-SD). The mixing behaviour of these excipients and their effect on flow and binder activity of paracetamol was assessed. The mean particle sizes of PVP-Leu PVP-SD and PVP were 2.5, 2.1 and 21.9 μm, respectively. Surface composition characterization indicated that l -leucine achieved higher concentrations on the surface compared to the bulk of the PVP-Leu particles. The surface energy of PVP-Leu was significantly lower compared to PVP-SD. In addition, PVP-Leu exhibited a significantly lower bulk cohesion compared PVP-SD. The excipients were blended with paracetamol and qualitative characterization indicated that PVP-Leu blended more homogeneously with paracetamol compared to PVP-SD. Both PVP-Leu and PVP-SD then exhibited a significantly improved binder activity compared to PVP. The flow of the paracetamol was markedly improved with PVP-Leu while PVP-SD and PVP had negligible effect on its flow. This study reveals how physico-chemical and bulk properties of such prototype interactive excipients can play a key role in determining multi-factorial excipient performance.