Chitosan thermosensitive hydrogels based on lyophilizate powders demonstrate significant potential for clinical use in endoscopic submucosal dissection procedures.

The goal of this study was to develop intraoperative biomaterials for use in endoscopic submucosal dissection (ESD) procedures that are stable during storage, easy to use, and effective in clinical practice. Therefore, injectable thermosensitive hydrogels were developed based on lactobionic acid-modified chitosan/chitosan/ß-glycerophosphate (CSLA/CS/GP) hydrogel lyophilizate powders, and their properties were compared with original hydrogels that had not been freeze-dried. The results indicated that the lyophilizate powders retained their thermosensitive properties, and gels could be formed within 5 min at 37 °C. Compared to the original hydrogels, the injectability of the hydrogels derived from lyophilizate powders increased significantly. These novel materials maintained their original porous network lamellar structure but exhibited improved mechanical strength and tissue adhesion. Their application with L929 and GES-1 cells revealed that the lyophilizate powder hydrogels demonstrated good cytocompatibility and clearly protected the cells in an acidic environment. The results of submucosal injection experiments involving porcine stomach tissue indicated that the heights of the cushions created by CSLA/CS/GP lyophilizate powder hydrogels lasted longer than those generated with normal saline. The thermosensitive hydrogels based on lyophilizate powders may contribute to practical clinical applications involving ESD, and may also have potential value for other applications in the digestive tract.

Hydrothermal synthesis of hydroxyapatite powders using Response Surface Methodology (RSM).

Hydroxyapatite (HAp)-[Ca10 (PO4)6(OH) 2] has a similar chemical composition to bone material, making it the main mineral supplement in bone-making. Due to its high biocompatibility, hydroxyapatite is widely used in the repair of bone deficiencies and in the production of dental or orthopedic implants. In this research, hydroxyapatite nanopowder was synthesized using a hydrothermal technique. Fourier Transform Infrared Spectroscopy (FTIR) and transmission electron microscopy (TEM) were used to investigate the chemical structure and morphology of the synthesized hydroxyapatite powder. X-ray diffraction (XRD) was used to evaluate the phase analysis of HAp nanopowder. In addition, bioactivity HAp assessment was conducted by scanning electron microscopy (SEM) attached with Energy Dispersive X-Ray Spectroscopy (EDX) analysis. Response Surface Methodology (RSM) with central composite design (CCD) was used in order to determine the optimal conditions for yield, size, and crystallinity. Three independent variables (pH, temperature, and hydrothermal treatment time) were investigated. The yield was observed to increase in alkaline conditions; pH showed the greatest influence on the yield, size, and crystallinity of the synthesized hydroxyapatite, based on Analysis of Variance. The results of bioactivity evaluation are showed high bioactivity due to the formation of apatite on the surface of the synthesized nanopowder.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability.

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.

Real-time monitoring of pharmaceutical properties of medical tablets during direct tableting process by hybrid tableting process parameter-time profiles.

BACKGROUND: Real-time monitoring is required for the pharmaceutical manufacturing process to produce high-quality pharmaceutical products. OBJECTIVE: Changes in the critical tableting process parameters of single-punch tableting machine due to variability in the moisture content of the raw powders were monitored by hybrid tableting pressure-time profiles. METHODS: After mixing of the raw powders, which consisted of theophylline, anhydrous lactose, potato starch and crystalline cellulose, they were stored at 0%, 45%, or 75% relative humidity (RH) for 24 h, respectively. Continuous tablet productions were carried out using the mixed powder samples at 10%, 45%, or 75% RH, respectively. The critical process parameters, such as upper and lower puncture pressures, die wall pressures, and inter-punch distances were recoded with the tableting machine, and then, tablet hardness (H), weight (W) and disintegration time (DT) of the tablets were measured. RESULTS: Hybrid tableting pressure-time profiles were obtained from various critical process parameters, and calibration models to predict pharmaceutical properties were calculated based on the hybrid profiles using a partial-least-squares regression (PLSR) method. In addition, the consistency of the calibration models were verified by constructing robust calibration models. CONCLUSION: Informetrical analysis for tablets based on hybrid tableting pressure-time profiles could evaluate the change of tablet properties dependent on the moisture content in the raw powders during the tableting process. The changes of tableting properties and elasticity were caused by agglomeration of powder particles at moisture content.

Synthesis of ZnO/Fe3O4/rGO nanocomposites and evaluation of antibacterial activities towards E. coli and S. aureus.

Antibacterial activity of nanoparticles (NPs) and nanocomposites (NCs) has received wide spread attention in biomedical applications. In this direction, the authors prepared zinc oxide (ZnO), iron oxide (Fe3O4), and their composite including reduced graphene oxide (rGO) by hydrothermal method. The structural and microstructural properties of the synthesised NPs and NCs were investigated by XRD, FT-IR, UV-Vis, TGA, and TEM analysis. PEG-coated ZnO and Fe3O4 form in hexagonal wurtzite and inverse spinel structures, respectively. ZnO forms in rod-shaped (aspect ratio of ∼3) morphology, whereas well-dispersed spherical-shaped morphology of ∼10 nm is observed in Fe3O4 NPs. The ZnO/Fe3O4 composite possesses a homogeneous distribution of above two phases and shows a very good colloidal stability in aqueous solvent. These synthesised particles exhibited varying antibacterial activity against gram-positive strain Staphylococcus aureus (S. aureus) and gram-negative strain Escherichia coli (E. coli). The nanocomposite exhibits a better cidal effect on E. coli when compared to S. aureus when treated with 1 mg/ml concentration. Further, the addition of rGO has intensified the anti-bacterial effect to a much higher extent due to synergistic influence of individual components.

New strategies for the construction of eggshell powder reinforced starch based fire hazard suppression biomaterials with tailorable thermal, mechanical and oxygen barrier properties.

A novel eco-friendly approach is highlighted for synthesizing chicken eggshell powder (EP) modified starch-g-poly(N-isopropylacrylamide) (starch-g-PNIPAAm) bionanocomposites (BNCs) by emulsifier-free emulsion polymerisation and aiming to study the effect of EP on the properties of modified starch BNCs. Young's modulus and tensile strength of BNCs are found to be improved dramatically. The enhanced char forming ability of EP improves the thermal stability of BNCs at high temperature as investigated by thermogravimetric analyses carried out in inert atmosphere. The cone calorimeter test revealed that the 4% w/v EP-based BNC resulted suppression on fire hazards in terms of reduction in PHRR (decreased by 33.3%), PSPR (decreased by 75.3%) compared with those of the control starch-g-PNIPAAm and could be attributed to the insulating barrier effect of EP. In addition, the fire retardancy of the BNCs is investigated from limiting oxygen index (LOI) test. The surface morphology and the elemental content of the collected char residues of BNCs after fire retardant test is analysed by FESEM and EDX. Further the oxygen barrier property of BNC with 4% w/v EP is reduced by 73% compared to starch-g-PNIPAAm. The resulting nanostructure and molecular interactions in the BNCs are analysed by FTIR, XRD and TEM.

Fabrication of porous NiTi biomedical alloy by SHS method.

Having similar properties with natural bone, has made porous NiTi shape memory alloy (SMA) a promising material for biomedical applications. In this study porous NiTi SMA has synthesized with 30 and 40 vol.% green porosity by self propagating high temperature synthesis (SHS) from elemental Ni and Ti powders. After synthesizing, the average porosity of specimens reached to 36.8 and 49.8% for green compacts with 30 and 40 vol.% of green porosity, respectively. Combustion products were characterized by XRD, SEM, EDS and electrochemical polarization test. Although desired B2 (NiTi) phase was the dominant phase, other phases like Ti2Ni, Ni3Ti and Ni4Ti3 are found. Electrochemical polarization analysis in simulated body fluids (SBF) shows that, synthesized porous NiTi has better corrosion resistance than solid one and hydroxy apatite coating on porous NiTi worsen electrochemical corrosion resistance which is because of bioactive behavior of hydroxy apatite.

3D plotting in the preparation of newberyite, struvite, and brushite porous scaffolds: using magnesium oxide as a starting material.

Calcium phosphate (CaP)-containing materials, such as hydroxyapatite and brushite, are well studied bone grafting materials owing to their similar chemical compositions to the mineral phase of natural bone and kidney calculi. In recent studies, magnesium phosphate (MgP)-containing compounds, such as newberyite and struvite, have shown promise as alternatives to CaP. However, the different ways in degradation and release of Mg2+ and Ca2+ ions in vitro may affect the biocompatibility of CaP and MgP-containing compounds. In the present paper, newberyite, struvite, and brushite 3D porous structures were constructed by 3D-plotting combining with a two-step cementation process, using magnesium oxide (MgO) as a starting material. Briefly, 3D porous green bodies fabricated by 3D-plotting were soaked in (NH4)2HPO4 solution to form semi-manufactured 3D porous structures. These structures were then soaked in different phosphate solutions to translate the structures into newberyite, struvite, and brushite porous scaffolds. Powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS) were used to characterize the phases, morphologies, and compositions of the 3D porous scaffolds. The porosity, compressive strength, in vitro degradation and cytotoxicity on MC3T3-E1 osteoblast cells were assessed as well. The results showed that extracts obtained from immersing scaffolds in alpha-modified essential media induced minimal cytotoxicity and the cells could be attached merely onto newberyite and brushite scaffolds. Newberyite and brushite scaffolds produced through our 3D-plotting and two-step cementation process showed the sustained in vitro degradation and excellent biocompatibility, which could be used as scaffolds for the bone tissue engineering.

Colloids or powders: Which nanoparticle formulations do cells like more?

Understanding the difference in physicochemical properties and biological response between colloidal and powder formulations of identical materials is important before the given materials are used in a medical milieu. In this study we compared a set of biological effects of colloidal and powder formulations of composite nanoparticles comprising superparamagnetic iron oxide cores and silicate/carbon shells. Magnetic dipole interaction between adjacent nanoparticles was more pronounced in their powders than in their colloidal formulations. Nanoparticles delivered as powders were thus more responsive to the magnetic field, but exhibited reduced uptake in bone and brain cancer cells, including K7M2 osteosarcoma line and U87 and E297 glioblastoma lines. Specifically, while the alternate magnetic field elicited a more rapid heat generation in cell culture media supplemented with the magnetic powders, the nanoparticles dispersed in the same media were uptaken by the cancer cells more copiously. The cellular uptake proved to be more crucial in defining the effect on cell survival, given that suspended formulations elicited a greater degree of cancer cell death in the magnetic field compared to the powder-containing formulations. Because of this effect, colloidal formulations were able to target cancer cells more effectively than the powders: they reduced the viability of all three tested cancer cell lines to a significantly greater degree that the viability of the normal, MDCK-MDR1 cell line. It is concluded that better uptake profile can make up for the lower heating rate in the AC field and lead to a more effective magnetic hyperthermia therapy. These results also demonstrate that the direct delivery of ferrofluids is more optimal than the administration of their constitutive particles as powders.

Nitinol powders generate from Plasma Rotation Electrode Process provide clean powder for biomedical devices used with suitable size, spheroid surface and pure composition.

The nickel-titanium alloy (57Ni-43Ti in wt%) was atomized by the plasma rotating electrode process (PREP). The PREP parameters such as plasma arc current, rotating electrode speed with corresponding PREP powder size range in weight percentage analysis, powder morphology and biocapability of cells were studied by scanning electron microscopies, Inductively Coupled Plasma and X-ray diffraction techniques. From the electrode of the produced powders, the composition has no obviously changes. Weight percentage up to 31.8% of the range under 300 µm while the rotation electrode speed increase to 12k rpm. Spherical and flat with smooth surface were observed in different size range. Brittle phase was not observed of XRD data. The nitinol powder has high biocapability with cells showed no cytotoxicity and well cell adhesion in the in vivo assay.

Optimization of Premix Powders for Tableting Use.

Direct compression is a popular choice as it provides the simplest way to prepare the tablet. It can be easily adopted when the active pharmaceutical ingredient (API) is unstable in water or to thermal drying. An optimal formulation of preliminary mixed powders (premix powders) is beneficial if prepared in advance for tableting use. The aim of this study was to find the optimal formulation of the premix powders composed of lactose (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) by using statistical techniques. Based on the "Quality by Design" concept, a (3,3)-simplex lattice design consisting of three components, LAC, CS, and MCC was employed to prepare the model premix powders. Response surface method incorporating a thin-plate spline interpolation (RSM-S) was applied for estimation of the optimum premix powders for tableting use. The effect of tablet shape identified by the surface curvature on the optimization was investigated. The optimum premix powder was effective when the premix was applied to a small quantity of API, although the function of premix was limited in the case of the formulation of large amount of API. Statistical techniques are valuable to exploit new functions of well-known materials such as LAC, CS, and MCC.

3D powder printed tetracalcium phosphate scaffold with phytic acid binder: fabrication, microstructure and in situ X-Ray tomography analysis of compressive failure.

One of the important aspects in 3D powder printing (3DPP) is the selection of binder for a specific material composition to produce scaffolds with desired microstructure and physico-chemical properties. To this end, a new powder-binder combination, namely tetracalcium phosphate (TTCP) and phytic acid (IP6) was investigated at ambient temperature, for low load bearing application. A minimal deviation (<200 µm, w.r.t. computer aided design) was observed in the final sample through optimization of 3DPP process, along with minimum strut and macro-pore size of 200 and 750 µm, respectively. Importantly, the printed scaffolds exhibited compressive strength of 4-8.5 MPa (in the range of cancellous bone) and in vitro dissolution experiments in phosphate buffered saline (PBS) upto one month revealed gradual degradation in strength property. The TTCP scaffolds are characterized to be moderately porous (~40%) with high interconnectivity, which is essential for vascularization and good osteoconductivity. Another major aim of this study was to demonstrate the failure mechanism of 3D powder-printed scaffolds using monotonic and intermittent compression coupled with micro-computed tomography (µCT) imaging. Analyzing these results, we have demonstrated the origin of crack generation and propagation under compressive loading in relation to the unique microstructure, obtained through 3DPP. These findings enable us to acquire a deeper insight of the relationship between structural attributes and failure behavior, to further tailor the 3D powder printing process for ceramic biomaterials.

Synthesis of submicron silver powder from scrap low-temperature co-fired ceramic an e-waste: Understanding the leaching kinetics and wet chemistry.

The current study focuses on the understanding of leaching kinetics of metal in the LTCC in general and silver leaching in particular along with wet chemical reduction involving silver nanoparticle synthesis. Followed by metal leaching, the silver was selectively precipitated using HCl as AgCl. The precipitated AgCl was dissolved in ammonium hydroxide and reduced to pure silver metal nanopowder (NPs) using hydrazine as a reductant. Polyvinylpyrrolidone (PVP) used as a stabilizer and Polyethylene glycol (PEG) used as reducing reagent as well as stabilizing reagent to control size and shape of the Ag NPs. An in-depth investigation indicated a first-order kinetics model fits well with high accuracy among all possible models. Activation energy required for the first order reaction was 21.242 kJ mol-1 for Silver. PVP and PEG 1% each together provide better size control over silver nanoparticle synthesis using 0.4 M hydrazine as reductant, which provides relatively regular morphology in comparison to their individual application. The investigation revealed that the waste LTCC (an industrial e-waste) can be recycled through the reported process even in industrial scale. The novelty of reported recycling process is simplicity, versatile and eco-efficiency through which waste LTCC recycling can address various issues like; (i) industrial waste disposal (ii) synthesis of silver nanoparticles from waste LTCC (iii) circulate metal economy within a closed loop cycle in the industrial economies where resources are scarce, altogether.

Gelation Factors of Pectin for Development of a Powder Form of Gel, Dry Jelly, as a Novel Dosage Form.

Jellies for oral administration are dosage forms that contain water, as stipulated in the Japanese Pharmacopeia, and heat is generally applied to the jellies during the manufacturing process. Therefore, it is difficult to formulate drugs that may be affected adversely by water and/or heat. To solve this problem, we tried to develop a powder form of gel as a novel dosage form (dry jelly: jelly medicine extemporaneously prepared) that is converted to jelly after addition of water at the time of administration. For this purpose, a basic gel formulation consisting of pectin, glucono-δ-lactone, dibasic calcium phosphate hydrate, and sucrose was investigated to evaluate the critical factors affecting gelation phenomena. The gel form was developed by adjusting the amount of each component of the formulation and of water added. Gelation occurred even with hard water containing metal ions (hardness of approximately 304 mg/L), and no changes in gel hardness occurred. The desired gel hardness could be controlled by adjusting the amount of water. The gel hardness changed over time after the addition of water, but this change did not affect the dissolution behavior of drugs formulated in the dry jelly.

Different post-processing conditions for 3D bioprinted α-tricalcium phosphate scaffolds.

The development of 3D printing hardware, software and materials has enabled the production of bone substitute scaffolds for tissue engineering. Calcium phosphates cements, such as those based on α-tricalcium phosphate (α-TCP), have recognized properties of osteoinductivity, osteoconductivity and resorbability and can be used to 3D print scaffolds to support and induce tissue formation and be replaced by natural bone. At present, however, the mechanical properties found for 3D printed bone scaffolds are only satisfactory for non-load bearing applications. This study varied the post-processing conditions of the 3D powder printing process of α-TCP cement scaffolds by either immersing the parts into binder, Ringer's solution or phosphoric acid, or by sintering in temperatures ranging from 800 to 1500 °C. The porosity, composition (phase changes), morphology, shrinkage and compressive strength were evaluated. The mechanical strength of the post-processed 3D printed scaffolds increased compared to the green parts and was in the range of the trabecular bone. Although the mechanical properties achieved are still low, the high porosity presented by the scaffolds can potentially result in greater bone ingrowth. The phases present in the scaffolds after the post-processing treatments were calcium-deficient hydroxyapatite, brushite, monetite, and unreacted α-TCP. Due to their chemical composition, the 3D printed scaffolds are expected to be resorbable, osteoinductive, and osteoconductive.

Atomic scale surface engineering of micro- to nano-sized pharmaceutical particles for drug delivery applications.

Atomic layer deposition on pharmaceutical particles for drug delivery applications is demonstrated using assisted fluidized bed dry powder processing. Complete and conformal layering is achieved on particle sizes from the lower micron to upper nanometer range under near ambient conditions. As few as 2-14 atomic alumina layers alter particle properties: dissolution, dispersibility and heat transfer.

Aerodynamic Droplet Stream Expansion for the Production of Spray Freeze-Dried Powders.

In spray freeze-srying (SFD), a solution is sprayed into a refrigerant medium, frozen, and subsequently sublimation dried, which allows the production of flowable lyophilized powders. SFD allows commonly freeze-dried active pharmaceutical ingredients (e.g., proteins and peptides) to be delivered using new applications such as needle-free injection and nasal or pulmonary drug delivery. In this study, a droplet stream was injected into a vortex of cold gas in order to reduce the risk of droplet collisions and therefore droplet growth before congelation, which adversely affects the particle size distribution. Droplets with initial diameters of about 40-50 µm were frozen quickly in a swirl tube at temperatures around -75°C and volumetric gas flow rates between 17 and 34 L/min. Preliminary studies that were focused on the evaluation of spray cone footprints were performed prior to SFD. A 23 factorial design with a model solution of mannitol (1.5% m/V) and maltodextrin (1.5% m/V) was used to create flowable, low density (0.01-0.03 g/cm3) spherical lyophilisate powders. Mean particle diameter sizes of the highly porous particles ranged between 49.8 ± 6.6 and 88.3 ± 5.5 µm. Under optimal conditions, the mean particle size was reduced from 160 to 50 µm (decrease of volume by 96%) compared to non-expanded streams, whereas the SPAN value did not change significantly. This method is suitable for the production of lyophilized powders with small particle sizes and narrow particle size distributions, which is highly interesting for needle-free injection or nasal delivery of proteins and peptides.

Predicting the Occurrence of Sticking during Tablet Production by Shear Testing of a Pharmaceutical Powder.

Sticking is a failure of pharmaceutical production that occurs when a powder containing a large amount of adhesive is being tableted. This is most frequently observed when long-term tableting is carried out, making it extremely difficult to predict its occurrence during the tablet formula design stage. The efficiency of the pharmaceutical production process could be improved if it were possible to predict whether a particular formulation was likely to stick during tableting. To address this issue, in the present study we prepared tablets composed of blended ibuprofen (Ibu), a highly adhesive drug, and measured the degree of adherence of powder particles to the surface of the tablet punch. We also measured the shear stress of the powder to determine the practical angle of internal friction (Φp) of the powder bed as well as the angle of wall friction (Φw) relative to the punch surface. These values were used to define a sticking index (SI), which showed a high correlation with the amount of Ibu that adhered to the punch during tableting; sticking occurred at SI >0.3. When the amount of lubricant added to the formulation was changed to yield tablets exhibiting different SI values without changing the compounding ratio, sticking did not occur at SI ≤0.3. These results suggest that determining the SI of a pharmaceutical powder before tableting allows prediction of the likelihood of sticking during tableting.

Determination of the Nip Angle in Roller Compactors With Serrated Rolls.

In roller compaction, the nip angle defines the critical transition interface between the slip and nip regions which is used to model material densification behavior and the properties of compacted ribbons. Current methods to determine the nip angle require either sophisticated instrumentation on smooth rolls or input parameters that are difficult to obtain experimentally. In this study, a practical method to determine nip angles for serrated rolls was developed based on mass balance considerations established around the nip region. Experimental input relating to roll geometry, powder density, and mass output from the compactor were required and they could be obtained reliably. The calculated nip angles were validated against those obtained from physical measurements during actual roll compaction. These nip angles were in agreement for various powder formulations containing plastic and brittle materials. The nip angles ranged from 4° to 12° and decreased significantly when the proportion of brittle material increased. Nip angles were also calculated using the widely used Johanson model. However, wall friction measurement on serrated roll surfaces could be impractical. The Johanson model-derived nip angles could differ by 3°-8° just by altering the roughness of the reference wall and this had compromised their reliability.

Dry Powder Coating using Planetary Centrifugal Mixer.

PURPOSE: Extemporaneous compounding is an important part of pharmacy practice, and should be standardized and sophisticated to ensure the quality of the compounded preparations. Recently, we applied a planetary centrifugal mixer (PCM) to powder blending, which has attracted interest for its small scale and lack of contamination. In this study, we aimed to reveal the feasibility of dry powder coating through ordered mixing of fine particles using PCM. METHODS: Cohesive lactose powders (Pharmatose450M) were dry coated with magnesium stearate (MgSt) using from 0.1 to 5%(w/w) content. The operational variables tested were operation time (1-30 min), operation speed (400-1000 rpm), vessel size (24-100 mL), and charging rate in the vessel (20-40%). The processed powders were evaluated for their surface morphology, flowability, and wettability. Furthermore, fine ibuprofen particles were coated with various lubricants, and then the dissolution profiles were examined. The crystallinity of ibuprofen was assessed using FT-IR and PXRD. RESULTS: Lactose powders were successfully coated with MgSt using PCM. When the level of MgSt was over 1%, the surface of the lactose powders was thoroughly covered. Angles of repose were 51° and 41° for unprocessed and processed powders with 1% MgSt, respectively. The contact angle of the water drop on the 1% MgSt sample leached to be 132°, changing to a hydrophobic surface. Investigations under various operational conditions revealed that higher improvement was observed upon higher speed and longer time, and a smaller charging rate in the vessel. Vessel size had no impact. Moreover, improved dissolution of ibuprofen coated with both hydrophilic and hydrophobic lubricants was observed owing to good dispersing behavior. Besides, no alteration of crystallinity was detected. CONCLUSIONS: PCM is an effective tool for dry powder coating with low impact stress. The presented method will contribute a great deal to making crushed tablets a functional powder.