Iron Nano Biocomposite-Infused Biopolymeric Films: A Multifunctional Approach for Robust Skin Repair.

Sodium alginate (SA) biopolymeric films have various limitations such as poor mechanical properties, high vapor permeability, lack of antibacterial activity, excessive burst release, and weak cell adhesion. To overcome these limitations, a strategy involving the integration of nanofillers into an SA film matrix is explored. In this context, a cost-effective iron-containing carbon nano biocomposite (FeCNB) nanofiller is developed using a solvent-free technique. This nanocomposite is successfully incorporated into the alginate film matrix at varying concentrations (0.05, 0.1, and 0.15%) aimed at enhancing its physicochemical and biological properties for biomedical applications. Characterization through FESEM and BET analyses confirms the porous nature of the FeCNB. EDX shows the FeCNB's uniform distribution upon its integration into the film matrix, albeit without strong chemical interaction with SA. Instead, hydrogen bonding interactions become apparent in the FTIR spectra. By incorporating the FeCNB, the mechanical attributes of the films are improved and the water vapor permeability approaches the desired range (2000-2500 g/m2day). The film's swelling ratio reduction contributes to a decrease in water permeability. The antibacterial activity and sustained release property of the FeCNB-incorporated film are established using tetracycline hydrochloride (TCl), a model drug. The drug release profile resembled Korsmeyer-Peppas's release pattern. In vitro assessments via the MTT assay and scratch assay on NIH-3T3 cells reveal that FeCNB has no adverse effects on the biocompatibility of alginate films. The cell proliferation and adhesion to the SA film are significantly enhanced after infusion of the FeCNB. The in vivo study performed on the rat model demonstrates improved wound healing by FeCNB-impregnated films. Based on the comprehensive findings, the proposed FeCNB-incorporated alginate films prove to be a promising candidate for robust skin repair.

TiB2-Derived Nanosheets Enhance the Tensile Strength and Controlled Drug Release of Biopolymeric Films Used in Wound Healing.

Wound healing using an alginate-based biopolymeric film is one of the most preferred treatments. However, these films lack mechanical strength (elasticity and tensile strength), show higher initial burst release, and exhibit high vapor permeability. The present study reports the development of nanosheets derived from titanium diboride (10 nm) (NTB)-incorporated biopolymeric films (0.025, 0.05, and 0.1% w/v) using sodium alginate (SA) and carboxymethyl cellulose (CMC) to overcome the shortfalls. The surface properties of the film, nanosheet distribution within the film, and possible interactions with the film are explored by using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). These analyses confirm that nanosheets are uniformly distributed in the film and introduce unevenness on the film's surface. The tensile strength of the nanosheet-incorporated film (0.1% NTB film) using UTM is found to be 24.30 MPa (six times higher compared to the blank film), equivalent to human skin. The water vapor transmission rate of the film is also found to be in the desired range (i.e., 2000-2500 g/m2 day). The biocompatibility of the NTB film is confirmed by the MTT assay test using NIH/3T3 cells and HEK 293 cells. Furthermore, the scratch assay shows that the developed films promote cell migration and proliferation. The antibacterial activity of the film is also demonstrated using a model drug, tetracycline hydrochloride (TCl). Besides, the film exhibits the sustained release of TCl and follows the Korsmeyer-Peppas model for drug release. Overall, the 0.1% w/v NTB film is easy to fabricate, biocompatible and shows superior mechanical properties.

pH-Responsive and Reversible A-Motif-Based DNA Hydrogel: Synthesis and Biosensing Application.

Functional DNA hydrogels with various motifs and functional groups require perfect sequence design to avoid cross-bonding interference with themselves or other structural sequences. This work reports an A-motif functional DNA hydrogel that does not require any sequence design. A-motif DNA is a noncanonical parallel DNA duplex structure containing homopolymeric deoxyadenosines (poly-dA) strands that undergo conformation changes from single strands at neutral pH to a parallel duplex DNA helix at acidic pH. Despite this and other advantages over other DNA motifs like no cross-bonding interference with other structural sequences, the A-motif has not been explored much. We successfully synthesized a DNA hydrogel by using an A-motif as a reversible handle to polymerize a DNA three-way junction. The A-motif hydrogel was initially characterized by electrophoretic mobility shift assay, and dynamic light scattering, which showed the formation of higher-order structures. Further, we used imaging techniques like atomic force microscopy and scanning electron microscope to validating its hydrogel like highly branched morphology. pH-induced conformation transformation from monomers to gel is quick and reversible, and was analysed for multiple acid-base cycles. The sol-to-gel transitions and gelation properties were further examined in rheological studies. The use of the A-motif hydrogel in the visual detection of pathogenic target nucleic acid sequence was demonstrated for the first time in a capillary assay. Moreover, pH-induced hydrogel formation was observed in situ as a layer over the mammalian cells. The proposed A-motif DNA scaffold has enormous potential in designing stimuli-responsive nanostructures that can be used for many biological applications.

Newly developed nano-biocomposite embedded hydrogel to enhance drug loading and modulated release of anti-inflammatory drug.

A newly developed iron-based nano-biocomposite (nano Fe-CNB) impregnated alginate formulation (CA) is proposed to improve drug loading and exhibit pH-responsive behavior of model anti-inflammatory drug-ibuprofen for controlled release applications. The proposed formulation is investigated with conventional ß-CD addition in CA. The nano Fe-CNB-based formulations with and without ß-CD, (Fe-CNB ß-CD CA and Fe-CNB CA) are compared with only CA and ß-CD incorporated CA formulations. The results indicate the incorporation of nano-biocomposite or ß-CD into CA enhances the drug loading (>40%). However, pH-responsive controlled release behavior is observed for nano Fe-CNB based formulations only. The release studies from Fe-CNB ß-CD CA indicate ∼ 45% release in stomach pH (1.2) within 2 h. In contrast, Fe-CNB CA shows ∼20% release only in stomach pH and improved release (∼49%) at colon pH (7.4). The rheology and swelling studies indicate Fe-CNB CA remains intact in stomach pH with a minimal drug release, but it disintegrates at colon pH due to charge reversal behavior of nano-biocomposite and ionization of polymeric chains. Thus, Fe-CNB CA formulation is found to be a potential candidate for targeting colon delivery, inflammatory bowel disease, and post-operative conditions.

Application of Twin-Screw Melt Granulation to Overcome the Poor Tabletability of a High Dose Drug.

Pharmaceutical tablet manufacturing has seen a paradigm shift toward continuous manufacturing and twin-screw granulation-based technologies have catalyzed this shift. Twin-screw granulator can simultaneously perform unit operations like mixing, granulation, and drying of the granules. The present study investigates the impact of polymer concentration and processing parameters of twin-screw melt granulation, on flow properties and compaction characteristics of a model drug having high dose and poor tabletability. Acetaminophen (AAP) and polyvinylpyrrolidone vinyl acetate (PVPVA) were used as a model drug (90-95% w/w) and polymeric binder (5-10%w/w), respectively, for the current study. Feed rate (~650-1150 g/h), extruder screw speed (150-300 rpm), and temperature (60-150°C) were used as processing variables. Results showed the reduction in particle size of drug in the extrudates (D90 of 15-25 µm from ~80 µm), irrespective of processing condition, while flow properties were a function of polymer concentration. Overall, good flowability of the products and their tablets with optimum tensile strength can be obtained through using high polymer concentration (i.e., 10% w/w), lower feed rate (~650 g/h), lower extruder screw speed (150 rpm), and higher processing temperatures (up to 120°C). The findings from the current study can be useful for continuous manufacturing of tablets of high dose drugs with minimal excipient loading in the final dosage form.

Designer DNA Hydrogels Stimulate 3D Cell Invasion by Enhanced Receptor Expression and Membrane Endocytosis.

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA-based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by the increase in cellular area by almost two-fold followed by an increase in the receptor expression, the endocytosis, and the 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cell programming and regenerative therapeutics.

Stimuli Responsive, Programmable DNA Nanodevices for Biomedical Applications.

Of the multiple areas of applications of DNA nanotechnology, stimuli-responsive nanodevices have emerged as an elite branch of research owing to the advantages of molecular programmability of DNA structures and stimuli-responsiveness of motifs and DNA itself. These classes of devices present multiples areas to explore for basic and applied science using dynamic DNA nanotechnology. Herein, we take the stake in the recent progress of this fast-growing sub-area of DNA nanotechnology. We discuss different stimuli, motifs, scaffolds, and mechanisms of stimuli-responsive behaviours of DNA nanodevices with appropriate examples. Similarly, we present a multitude of biological applications that have been explored using DNA nanodevices, such as biosensing, in vivo pH-mapping, drug delivery, and therapy. We conclude by discussing the challenges and opportunities as well as future prospects of this emerging research area within DNA nanotechnology.

DNA-Functionalized Nanoparticles for Targeted Biosensing and Biological Applications.

Nanoscale systems have increasingly been used in biomedical applications, enhancing the demand for the development of biomolecule-functionalized nanoparticles for targeted applications. Such designer nanosystems hold great prospective to refine disease diagnosis and treatment. To completely investigate their potential for bioapplications, nanoparticles must be biocompatible and targetable toward explicit receptors to guarantee particular detecting, imaging, and medication conveyance in complex organic milieus, for example, living cells, tissues, and organisms. We present recent works that explore enhanced biocompatibility and biorecognition of nanoparticles functionalized with DNA and different DNA entities such as aptamers, DNAzymes, and aptazymes. We sum up the methods utilized in the amalgamation of complex nanostructures, survey the significant types of multifunctional nanoparticles that have been developed in the course of recent years, and give a perceptual vision of the significant field of nanomedicine. The field of DNA-functionalized nanoparticles holds an incredible guarantee in rising biomedical zones, for example, multimodal imaging, theranostics, and picture-guided treatments.

Role of randomly distributed nanoscale roughness for designing highly hydrophobic particle surface without using low surface energy coating.

Surface texture and surface chemistry both are important to design the highly hydrophobic surfaces. Tuning surface chemistry with chemical coating can improve the hydrophobic nature of the surface to a limit. Further increase in hydrophobicity requires an alteration in surface roughness. The present work proposes the randomly distributed nanoscale roughness for designing highly hydrophobic surface engineered particle (SEP) from the hydrophilic particle. An alkali medium is used to engineer the surface of the original particle (OP) for the different time intervals. The surface is thoroughly characterized by Scanning Electron Microscopy, Atomic Force Microscopy, X-Ray Photoelectron Spectroscopy, and contact angle (CA) measurement. Results reveal that the hydrophobic CA up to 147° can be tuned by nanoscale surface roughness even after Si-OH incorporation on the surface. Moreover, the silanization of the OP and SEP surface further identifies that a gradual increase in CA beyond 113° is due to the favorable nano-scale surface roughness and its distribution on the surface of SEP. The study is first of its kind to achieve highly hydrophobic micron-size particle surface (CA ~ 147°) without coating of any low surface energy material.

One-step dry synthesis of an iron based nano-biocomposite for controlled release of drugs.

Bio-based drug carriers have gained significant importance in Control Drug Delivery Systems (CDDS). In the present work, a new iron-based magnetic nano bio-composite (nano-Fe-CNB) is developed in a one-step dry calcination process (solventless) using a seaweed-based biopolymer. The detailed analysis of the developed nano Fe-CNB is carried out using FE-SEM, HR-TEM, P-XRD, XPS, Raman spectroscopy, FTIR etc. and shows that nano-Fe-CNB consists of nanoparticles of 5-10 nm decorated on 7-8 nm thick 2-D graphitic carbon material. The impregnation of nano-Fe-CNB into the calcium alginate (CA) hydrogel beads is found to have good drug loading capacity as well as pH responsive control release behavior which is demonstrated using doxorubicin (DOX) as a model cancer drug. The drug loading experiments exhibit ∼94% loading of DOX and release shows ∼38% and ∼8% release of DOX at pH 5.4 and 7.4 respectively. The developed nano Fe-CNB facilitates strong electrostatic interactions with cationic DOX molecules at pH 7.4 and thereby restricts the release of the drug at physiological pH. However, at cancer cell pH (5.4), the interaction between the drug and nano-Fe-CNB reduces which facilitates more drug release at pH 5.4. Thus, the developed nano-biocomposite has the potential to reduce the undesired side effects associated with faster release of drugs.

Functional DNA Based Hydrogels: Development, Properties and Biological Applications.

DNA-based nanostructures have emerged as a versatile component for nanoscale construction of soft materials. Multiple structural, functional properties and versatility in conjugation with other biomolecules made DNA the material of choice to use in various biomedical applications. DNA-based hydrogels significantly attracted attention in recent years owing to their properties and applications in biosensing, bioimaging, and therapeutics. Here, we summarize the recent advances in the area of DNA hydrogels where these are used either as structural material or as functional entities to make hybrid constructs with various biomedical applications. Multiple synthetic routes for constructing DNA hydrogels are summarized first, where the structural motifs and spatial arrangements are considered for the classification of DNA materials. We then present the characterization and properties of DNA hydrogels using multiple imaging and biophysical techniques. Further, different biomedical applications of DNA hydrogels are presented such as biosensing, bioimaging, and targeted drug delivery and as scaffolds to program cellular systems. Last, we discuss the vision and potential of DNA based hydrogels as an emerging class of therapeutically important devices for theragnostic and other biological applications.

A Non-electric and Affordable Surface Engineered Particle (SEP) based Point-of-Use (POU) Water Disinfection System.

Access to safe drinking water is still a distant dream to millions of people around the world. Especially, people from the low-income group in the developing countries remain deprived of this fundamental right and causes millions of death. There is an urgent need to develop affordable and easy to handle water filter which can provide desired drinking water quality without any electricity. In the present work, a simple and low-cost surface engineered particle (SEP) based filter is developed via alkali treatment of soda-lime-silica particle. The SEP based filter can be used as a portable, non-electric, gravity-driven Point-of-Use (POU) water disinfection system. The developed SEP-based filter is capable to arrest the 99.48% (~2 to 2.5 log10 reduction) of gram-negative bacteria Escherichia coli (E. coli OP50) on its surface from the water containing 3 × 108 cells/ml. No bacterial regrowth is observed in the purified water for 12 h. The performance of SEP bed filter is implicated to the nano-scale surface roughness, its distribution along with the surface charge and surface hydrophobicity which are favorable to attract and adhere the bacteria in the flowing water. The observation is consistent over multiple filtration cycles indicating the suitability of SEP based bed filter for POU water disinfection. The SEP surface with 0.05 mM Ag+ loading (SEP+) completely inactivated (>99.99999%) bacteria and protects any bacteria recontamination in the purified water for its long term usage. The strong and effective silver binding property of SEP surface enables very minimal silver loading and eliminates any health hazard due to low silver leaching (~50 ppb) which is well below the drinking water equivalent level (DWEL ≤ 100 ppb). In rural and urban slum areas of developing countries where no water purification system exists prior to consumption, the easy-to-implement and affordable SEP-based gravity-driven non-electric point-of-use water purifier (materials cost ~ 0.25 USD) can be used to protect millions of lives from water borne diseases.

Influences of Crystal Anisotropy in Pharmaceutical Process Development.

Crystalline materials are of crucial importance to the pharmaceutical industry, as a large number of APIs are formulated in crystalline form, occasionally in the presence of crystalline excipients. Owing to their multifaceted character, crystals were found to have strongly anisotropic properties. In fact, anisotropic properties were found to be quite important for a number of processes including milling, granulation and tableting. An understanding of crystal anisotropy and an ability to control and predict crystal anisotropy are mostly subjects of interest for researchers. A number of studies dealing with the aforementioned phenomena are grounded on over-simplistic assumptions, neglecting key attributes of crystalline materials, most importantly the anisotropic nature of a number of their properties. Moreover, concepts such as the influence of interfacial phenomena in the behaviour of crystalline materials during their growth and in vivo, are still poorly understood. The review aims to address concepts from a molecular perspective, focusing on crystal growth and dissolution. It begins with a brief outline of fundamental concepts of intermolecular and interfacial phenomena. The second part discusses their relevance to the field of pharmaceutical crystal growth and dissolution. Particular emphasis is given to works dealing with mechanistic understandings of the influence of solvents and additives on crystal habit. Furthermore, comments and perspectives, highlighting future directions for the implementation of fundamental concepts of interfacial phenomena in the rational understanding of crystal growth and dissolution processes, have been provided.

Characterization of bulk and shear properties of basmati and non-basmati rice flour.

BACKGROUND: Flours are often unstable in relation to their flow performance, which is evident when a free-flowing material ceases to flow and the processing, handling, and production parameters depend on the inherent powder characteristics and their bulk behaviour. The present study was conducted to compare the flowability of basmati and non-basmati rice flour affecting bulk handling, which could be related to its particle size, shape and surface roughness (measured by atomic force microscopy) as well as bulk and shear properties, depending upon the processing conditions. RESULTS: Particle size (171.1-171.9 µm) of both samples was not significantly different. However, the flowability of the non-basmati rice flour was significantly affected by its particle shape (circularity 0.487), surface roughness (124.23 nm) and compressibility (25.32%) in comparison to basmati rice flour (circularity 0.653, surface roughness 113.59 nm and compressibility 21.09%), making it more cohesive than basmati rice flour. Also, basic flow energy was significantly higher in non-basmati flour, thus requiring more energy (147.54 mJ) to flow than basmati rice flour (130.15 mJ). CONCLUSION: Overall, flowability was analysed by applying three different pressures (3, 6 and 9 kPa), among which non-basmati rice flour was found to be less flowable (flow function coefficient (FFC) 2.33 at 9 kPa) in comparison to basmati (FFC 3.35 at 9 kPa), making bulk handling difficult. This study could be useful in designing processing equipment, hoppers and silos for rice flour handling. © 2017 Society of Chemical Industry.

Improving the wetting and dissolution of ibuprofen using solventless co-milling.

The wetting and dissolution of a BCS class II drug (Ibuprofen) is enhanced by solventless solid dispersion technique using co-milling. The co-milling is performed in a planetary ball mill using 1:1wt. ratio of Ibuprofen (drug) and Microcrystalline cellulose, MCC (excipient). The improvement in wettability and dissolution after co-milling are compared with the raw ibuprofen, ball-milled ibuprofen without any excipient and v-blend mixture of ibuprofen with an excipient. The changes in crystal level properties and reduction in crystallinity due to co-milling are measured using Powder X-ray diffraction (P-XRD) and Differential Scanning Calorimetry (DSC) respectively. The increased interaction between ibuprofen and MCC as well as hydrogen bond formation is confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The morphological changes are observed by optical microscopy and Field Emission Scanning Electron Microscopy (FESEM). The miscibility of drug and excipient and evidence of formation of glassy solutions are demonstrated by Modulated Temperature Differential Scanning Calorimetry (MTDSC) and Raman microscopy. The surface energy and wetting properties are determined using Inverse Gas Chromatography (IGC) and sessile drop method respectively. The results show that co-milling generates defects, strain, and reduction in crystallite size (changes in crystal level properties) which are responsible for the improvement of wetting and dissolution (96% in 90min). Also, with increase in co-milling time, the polar surface energy increases and the hydrophobic ibuprofen drug surface transforms into hydrophilic surface due to increase in OH groups of MCC on the ibuprofen surface. The present work quantified all the above-mentioned parameters including the acidic and basic parameters of co-milled ibuprofen using IGC. The technique improves the wetting and dissolution of hydrophobic drugs. It can be very well extended to BCS class II and IV drugs in the presence of different hydrophilic excipients.

Influence of particle properties on powder bulk behaviour and processability.

Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.

Fine powder flow under humid environmental conditions from the perspective of surface energy.

The influence of humidity on surface energetics and flow behavior of fine pharmaceutical powders was investigated. Amorphous and crystalline fine powders with hydrophilic (Corn starch and Avicel PH105) and hydrophobic (ibuprofen) nature were considered for this study. The surface energy was determined using surface energy analyzer and flow behavior was measured in terms of unconfined yield stress (UYS) using a shear tester. The study showed that unlike hydrophobic ibuprofen powder, surface energy and flow of hydrophilic excipient powders were affected by relative humidity (RH). The Lifshitz-van der Waals dispersive (γ(LW)) component of surface energy barely changed with varying RH for all pharmaceutical powders. For hydrophilic excipients, the specific component of surface energy (γ(SP)) was found to increase with increasing RH. Furthermore, for these excipients, flow deterioration at elevated RH was observed due to increased capillary bridge formation. Detailed analysis showed that γ(SP) component of surface energy can be an effective indicator for flow behavior of fine powders under varying humid conditions. The present study also brought out the existence of different regimes of probable interparticle forces which dictate the bulk flow behavior of fine hydrophilic powder under humid conditions.

Influence of surface modification on wettability and surface energy characteristics of pharmaceutical excipient powders.

Influence of surface modification on wettability and surface energy characteristics of three micron size pharmaceutical excipient powders was studied using hydrophilic and hydrophobic grades of nano-silica. The wetting behavior assessed from contact angle measurements using sessile drop and liquid penetration (Washburn) methods revealed that both techniques showed similar wettability characteristics for all powders depending on the hydrophilic or hydrophobic nature of nano-coating achieved. The polar (γs(p)) and dispersive (γs(d)) components of surface energies determined using extended Fowke's equation with contact angle data from sessile drop method and inverse gas chromatography (IGC) at infinite dilution suggested a general trend of decrease in γs(d) for all the surface modified powders due to passivation of most active sites on the surface. However, depending on the nature of the functional groups present in nano-silica, γs(p) was found to be either higher or lower for hydrophilic or hydrophobic coating respectively. Results show that wettability increases with increasing γs(p). Both the techniques of surface energy determination provided comparable and similar trends in γs(p) and γs(d) components of surface energies for all excipients. The study also successfully demonstrated that surface wettability and energetics of powders can be modified by varying the level of surface coating.

Passivation of high-surface-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability.

Ibuprofen micronization with dry coating is investigated to examine its influence on passivation/stabilization of high-surface-energy sites and reduced cohesion. A fluid energy mill was used to micronize ibuprofen particles down to 5-28 µm with or without simultaneous nanosilica coating. Powder flow property and dispersibility were characterized using FT4 powder tester and Rodos/Helos laser diffraction particle sizer. Surface energy was characterized using a next generation inverse gas chromatography instrument. Uncoated micronized ibuprofen showed an increased Lifshitz-van der Waals (LW) dispersion component of surface energy with increasing milling intensity. In contrast, dry-coated milled powders showed a significant reduction in the LW component, whereas physical mixture of uncoated micronized ibuprofen and silica exhibited no reduction in surface energy, indicating that dry coating is necessary for the passivation of high-energy sites of ibuprofen created during micronization. Surface energy of pure micronized ibuprofen was highly heterogeneous, whereas dry-coated ibuprofen had greatly reduced heterogeneity. Micronization with dry coating also improved flowability and bulk density as compared with pure active pharmaceutical ingredient micronization without coating, or just blending with silica. Overall, dry coating leads to decreased cohesion and improved flowability because of reduced LW dispersive component of surface energy and creating nanoscale surface roughness.

Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading.

Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 µm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 µm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t(80) for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings.