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Studies of powder flow using a recording powder flowmeter and measurement of the dynamic angle of repose.

This paper describes the utility of the dynamic measurement of the angle of repose for pharmaceutical systems, using a variable rotating cylinder to quantify powder flow. The dynamic angle of repose of sodium chloride powder sieve fractions was evaluated using a variable rotating cylinder. The relationship between the static and the dynamic angle of repose is discussed. The dynamic angle of repose of six lots of a multivitamin preparation were compared for inter- and intralot variation. In both cases, no significant differences (p greater than 0.05) were observed. In the multivitamin formulation, lubricants at lower concentration levels did not show a significant effect (p greater than 0.05) on the dynamic angle of repose when compared with flow rates. The effect of different hopper sizes and geometry has been evaluated using the recording powder flowmeter. The results indicate that although different hoppers affect the quantitative nature of the results, the same general trends are apparent. Thus, it appears possible to use a recording powder flowmeter with small quantities of material to predict the effect of formulation and processing variables on the flow of production scale quantities. This paper does not describe a comprehensive evaluation of the pharmaceutical utility of measuring the dynamic angle of repose. However, the results discussed are not encouraging and suggest that the recording powder flowmeter is more sensitive to the effects of formulation and production variables on powder flow.

Chemistry, Pharmaceutical↗

Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2. Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients.

The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.

Administration, Inhalation↗

A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcellulose phthalate nanospheres.

PURPOSE: A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. METHODS: Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. RESULTS: Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. CONCLUSIONS: Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.

Administration, Inhalation↗

Optimization of an alum-adsorbed vaccine powder formulation for epidermal powder immunization.

PURPOSE: To develop stable and effective aluminum salt (alum)-adsorbed vaccine powder formulations for epidermal powder immunization (EPI) via a spray freeze-drying (SFD) process. METHODS: Powder properties were determined using particle size analysis, tap density, and scanning electron microscopy. Alum coagulation was monitored via optical microscopy and particle sedimentation. Protein analysis was determined by the BCA protein assay, SDS-PAGE, and an enzyme immunoassay. In vivo immunogenicity and skin reactogenicity were performed on hairless guinea pigs and pigs, respectively. RESULTS: SFD of hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide or aluminum phosphate using an excipient combination of trehalose/mannitol/dextran produced vaccine powders of dense particles and satisfactory powder flowability and hygroscopicity. This formulation also offered excellent long-term stability to the powder and the antigen. The two most important factors influencing alum particle coagulation are the freezing rate and the concentration of aluminum in the liquid formulation for SFD. The SFD vaccines, when delivered to hairless guinea pigs by EPI or injected intramuscularly after reconstitution, were as immunogenic as the original liquid vaccine. A further study showed that EPI with SFD alum-adsorbed diphtheria-tetanus toxoid vaccine was well tolerated, whereas needle injection of the liquid formulation caused persistent granuloma. CONCLUSIONS: Stabilization of alum-adsorbed vaccine by SFD has important implications in extending vaccination to areas lacking a cold chain for transportation and storage and may also accelerate the development of new immunization technologies such as EPI.

Adsorption↗

Effect of powder characteristics on the sinterability of hydroxyapatite powders.

The effect of different sintering conditions on the sintered density and microstructure of two different hydroxyapatite (HA) powders was examined. The powder characteristics of a laboratory synthesized HA powder (Lab HA) were low crystallinity, a bimodal particle size distribution, a median particle size of 22 microm and a high specific surface area (SSA) of 63 m2/g. By contrast, a commercial calcined HA (commercial HA) was crystalline and had a median particle size of 5 microm and a low SSA of 16 m2/g. The different powder characteristics affected the compactability and the sinterability of the two HA powders. Lab HA did not compact as efficiently as commercial HA, resulting in a lower green density, but the onset of sintering of powder compacts of the former was approximately 150 degrees C lower than the later. The effect of compaction pressure, sintering temperature, time and heating rate on the sintered densities of the two materials was studied. Varying all these sintering conditions significantly affected the sintered density of commercial HA, whereas the sintered density of Lab HA was only affected significantly by increasing the sintering temperature. The Vickers hardness, Hv, of Lab HA was greater than commercial HA for low sintering temperatures, below 1200 degrees C, whereas for higher sintering temperatures the commercial HA produced ceramics with greater values of hardness. These trends can be related to the sinterability of the two materials.

Journal Article↗

A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending. Part I: D-optimal design for characterization of powder mixing and preliminary spectral data evaluation.

Experimental design, multivariate data acquisition, and analysis in addition to real time monitoring and control through process analyzers, represent an integrated approach for implementation of Process Analytical Technology (PAT) in the pharmaceutical industry. This study, which is the first in a series of three parts, uses an experimental design approach to identify critical factors affecting powder blending. Powder mixtures composed of salicylic acid and lactose were mixed in an 8 qt. V-blender. D-optimal design was employed to characterize the blending process, by studying the effect of humidity, component concentration, and blender speed on mixing end point. Additionally, changes in particle size and density of powder mixtures were examined. A near-infrared (NIR) fiber-optic probe was used to monitor mixing, through multiple optical ports on the blender. Humidity, component concentration, and blender speed were shown to have a significant impact on the blending process. Furthermore, humidity and concentration had a significant effect on particle size and density of powder mixtures. NIRS was sensitive to changes in physicochemical properties of the mixtures, resulting from process variables. Proper selection of NIR spectral preprocessing is of ultimate importance for successful implementation of this technology in the monitoring and control of powder blending and is discussed.

Chemistry, Pharmaceutical↗

Relationship between powder surface characteristics and viscoelastic properties of powder-filled semisolids.

The viscoelastic properties of dispersions of powdered zinc oxide in anhydrous lanolin and colloidal sulfur in anhydrous lanolin were characterized by dynamic mechanical testing. The elastic shear modulus, G', viscous shear modulus, G", and loss tangent (damping), tan delta, were determined as a function of shear frequency, v, temperature, T, and volume fraction of powder, phi 2. A priori, it might be expected that zinc oxide and colloidal sulfur would elicit different viscoelastic properties due to their contrasting surface characteristics; zinc oxide has a hydrophilic surface and colloidal sulfur has a hydrophobic surface. Even though constitutive mathematical models, derived to predict the mechanical behavior of solid-filled polymeric materials, were not designed to account for differences in surface characteristics of the filler, the findings of these experiments show that these models are useful in explaining the differences in viscoelastic behavior of powder-filled semisolids due to surface characteristics of the filler. One model of particular value was the Kerner equation. With it, mechanisms were postulated for zinc oxide-zinc oxide interactions, sulfur-sulfur interactions, zinc oxide-anhydrous lanolin interactions, and sulfur-anhydrous lanolin interactions, within dispersions as a function of nu, T, and phi 2. In addition, damping was used to further identify the influence of temperature. Data obtained from three temperatures, where anhydrous lanolin exists in three different structural states, shows that the influence of the powder on damping is not only determined by the surface characteristics of the powder but also the structural state of anhydrous lanolin.

Chemical Phenomena↗

Comparative evaluations of powder and mechanical properties of low crystallinity celluloses, microcrystalline celluloses, and powdered celluloses.

The purpose of this study was to examine and compare the powder and mechanical properties of different batches of low crystallinity powdered cellulose (LCPC-S1 to LCPC-S5) with those of commercial microcrystalline celluloses (MCC) (Avicel PH-101, Avicel PH-102, Avicel PH-103, Avicel PH-301, Avicel PH-302, and Emcocel 90m) and powdered celluloses (PC) (Solka Floc BW-40 and Solka Floc BW-100). Both the LCPC and MCC products were aggregated powders, whereas, the PC materials showed a fibrous structure. The primary particles forming the LCPC aggregates, however, were smaller in size and showed a greater degree of coalescence between boundaries, than those forming the MCC aggregates. The LCPC materials had significantly higher bulk and tap densities and lower porosity values compared with the MCC materials. The yield pressure value calculated from the linear region of the Heckel curve for LCPC varied between 48 and 70 MPa, for Avicel and PC materials between, 80 and 106 MPa, and for Emcocel 90m was 48 MPa. These results suggest that the LCPC products and Emcocel 90m, compared with commercial MCC and PC excipients, undergo plastic deformation at relatively lower compression pressures. The total volume reduction (i.e. compressibility), determined by calculating the area under the Heckel curve (AUHC), however, was comparable for all materials, with the exception of the LCPC-S3, which owing to the low yield pressure value, showed the largest reduction in volume. With the exception of LCPC-S1 and Solka Floc BW-40, all the other materials formed compacts, whose strength ranged from about 522 to 799 MPa2. The strengths of LCPC-S1 and Solka Floc BW-40 compacts, in contrast, were 214 and 257 MPa2, respectively. Irrespective of the solid fraction levels, the LCPC compacts, in general, disintegrated much faster than the MCC and PC compacts. In conclusion, the results suggest that the new LCPC materials reported herein have powder properties that are quite different from the MCC and PC materials evaluated, and show clear potential as direct compression excipients.

Cellulose↗

Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder.

PURPOSE: To assess the pulmonary deposition and pharmacokinetics of an engineered PulmoSphere powder relative to standard micronized drug when delivered from passive dry powder inhalers (DPIs). METHODS: Budesonide PulmoSphere (PSbud) powder was manufactured using an emulsion-based spray-drying process. Eight healthy subjects completed 3 treatments in crossover fashion: 370 microg budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1) (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma budesonide concentrations were measured for 12 h after inhalation. RESULTS: Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9 (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder delivered at both flow rates from the Eclipse DPI was twice as efficiently deposited as pelletized budesonide delivered at 60 L x min(-1) from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud. CONCLUSION: Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.

Administration, Inhalation↗

Surface and chemical properties of surface-modified UHMWPE powder and mechanical and thermal properties of its impregnated PMMA bone cement, IV: effect of MMA/accelerator on the surface modification of UHMWPE powder.

In our previous study, we manufactured a reinforced poly(methylmethacrylate) (PMMA) bone cement with 3 wt% of the surface-modified ultra high molecular weight polyethylene (UHMWPE) powder to improve its poor mechanical and thermal properties resulting from unreacted methylmethacrylate (MMA), the generation of bubble and shrinkage, and high curing temperature. In the present study, the effect of ratios of MMA and N,N'-dimethyl-p-toluidine (DMPT) solutions in redox polymerization system was investigated for the surface modification of UHMWPE powder. We characterized physical and chemical properties of surface-modified UHMWPE powder and reinforced bone cements by a scanning electron microscope, ultimate tensile strength (UTS) and curing temperature (Tmax). It was found that UTSs (41.3-51.3 MPa) of the reinforced PMMA bone cements were similar to those (44.5 MPa) of conventional PMMA bone cement (control), as well as significantly higher (P < 0.05) than those (33.8 MPa) of 3 wt% unmodified UHMWPE powder-impregnated bone cement. In particular, the UTS of redox polymerization system using MMA/DMPT solution was better than that of radical system using MMA/xylene solution. Also, Tmax of the reinforced PMMA bone cements decreased from 103 to 72-84 degrees C. From these results, we confirmed that the surface-modified UHMWPE powder can be used as reinforcing agent to improve the mechanical and thermal properties of conventional PMMA bone cement.

Biomechanical Phenomena↗

Effect of rise in simulated inspiratory flow rate and carrier particle size on powder emptying from dry powder inhalers.

The purpose of this study was to evaluate the effect of carrier particle size and simulated inspiratory flow increase rate on emptying from dry powder inhalers (DPIs). Several flow rate ramps were created using a computer-generated voltage signal linked to an electronic proportioning valve with a fast response time. Different linear ramps were programmed to reach 30, 60, 90, and 120 L/minute over 1, 2, or 3 seconds. At the lower flow rates, 100-ms and 500-ms ramps were also investigated. Three DPIs, Spinhaler, Rotahaler, and Turbuhaler, were used to test the effect of flow rate ramp on powder emptying. To test the effect of carrier particle size, anhydrous lactose was sieved into 3 particle sizes, and 20 mg of each was introduced into #2 and #3 hard gelatin capsules for Spinhaler and Rotahaler, respectively. Emptying tests were also carried out using the on/off solenoid valve described in the United States Pharmacopeia (USP) (resulting in no ramp generation). Powder emptying increased from 9% to 46% for Rotahaler and 69% to 86% for Spinhaler from the shallowest (3 seconds to reach peak flow) to the 100-ms ramp for the 53- to 75 microm lactose size range at 30 L/minute. Similar trends were observed for larger particle size fractions at the same flow rate. However, at higher airflow rates (60, 90, and 120 L/minute), there was no significant increase in percentage of emptying within the ramps for a particular particle size range. Trends observed were similar for placebo-filled Turbuhaler and commercially available Rotacaps used with Rotahaler, with the steepest ramp demonstrating more complete emptying. Percentage of powder emptying determined by the USP solenoid valve overestimated the emitted dose compared with the ramp method at 30 L/minute for all 3 devices. Results indicate that there is a significant difference in powder emptying at 30 L/minute from the shallowest to the steepest ramp within a particular size range. Within a particular particle size range, the USP method produced more complete emptying than even the steepest ramp, especially at the lower flow rates. Thus, when the USP device is used to estimate DPI emptying at lower flow rates, the results are likely to overestimate DPI performance significantly.

Analysis of Variance↗

[Determination of the artificial bezoar powder in the bezoar powder by near-infrared diffuse reflectance spectrometry].

OBJECTIVE: To establish a method determinating the artificial bezoar powder in the bezoar powder by near-infrared diffuse reflectance spectrometry. METHODS: The calibration set and the test set were set up by adding unequal artificial bezoar powder to the bezoar powder (content range: 0% - 100%), collecting the NIR spectrum of the samples. A mathematical model with partial least squares (PLS) was established to predict the test set. RESULTS: The coefficients of determination (R2) is 99.42 and the relative mean prediction error (RMSECV) is 1.93 respectively for the internal cross-validation set obtained. The coefficients of determination (R2) is 99. 9 and the relative mean standard error prediction (RMSEP) is 0.797, respectively for the test set obtained. The correlation coefficient between true and prediction is 0. 9972. CONCLUSION: This method is reliable and can be used to control the quality of preparations of bezoar powder.

Animals↗

[Powder-induced anaphylactic shock following use of powdered latex gloves during gynecological open laparotomy].

A 42-year-old woman with hysteromyoma underwent total abdominal hysterectomy under general and epidural anesthesia. Three years before, she had undergone resection of lipoma on her left shoulder under local anesthesia uneventfully. She had no previous history of hypersensitivity. General anesthesia was induced by intravenous injection of fentanyl, propofol, and vecuronium followed by inhalation of nitrous oxide, oxygen, and sevoflurane. Lidocaine and fentanyl were injected through a lumbar epidural catheter. After the start of open laparotomy, there was a sudden onset of hypotension. Administrations of ephedrine and phenylephrine, and volume loading were ineffective. Moreover, she showed profound hypotension, tachycardia, oxygen desaturation, decreased endtidal carbon dioxide and increased airway pressure. She broke out in a sweat with flushing on her chest and upper extremities. Therefore, we interrupted the surgery, checked her arterial blood gas analysis, performed echocardiography, and inserted a pulmonary artery catheter. We made a diagnosis of anaphylactic shock and administered methylprednisolone, albumin, epinephrine, norepinephrine, and dopamine to treat the circulatory collapse. The gynecologists changed their surgical gloves from a powdered-latex type to a powder-free latex type, and the surgery was resumed. She responded well to appropriate emergent therapy and all vasopressor drugs were gradually decreased and eventually stopped. After the end of the surgery, she recovered completely from the signs and symptoms of shock. Later, we found a high level of plasma latex protein-specific IgE antibody and confirmed the events as anaphylactic shock due to latex. We assumed that the anaphylactic shock was powder-induced latex allergy following use of powdered latex gloves in this case. Latex allergy should be suspected if an anaphylactic reaction or shock accompanied by circulatory collapse, respiratory failure, and skin symptoms of unknown origin occurs during surgery. As women more often come into contact with household articles containing latex, we suspect that women are prone to developing sensitivity towards latex. We recommend that powder-free or latex-free surgical gloves should be available not only for patients with a high risk of developing latex allergy, but also for patients indicated for gynecological open laparotomy.

Adult↗

[Determination of the artificial bezoar powder in bezoar powder by near-infrared spectrometry and support vector machine].

A method for determining the artificial bezoar powder in bezoar powder using near-infrared (NIR) diffuse reflectance spectrometry was proposed in the present paper. The method was based on support vector machine (SVM). The calibration set was set up by adding unequal artificial bezoar powder to the bezoar powder (content range: 0%-100% ) and collecting the NIR spectrum of the samples in the wave number range of 4000-10000 cm(-1). The processing algorithm was wavelet transform with first and second derivatives. A mathematical model with support vector machine was established. The model was checked with leave one method. The sum of the square of the relative prediction error was 0.00135. This method is reliable and can be used to control the quality of bezoar powder.

Animals↗

Static mechanical properties of hydroxyapatite (HA) powder-filled acrylic bone cements: effect of type of HA powder.

This work reports on the effect of the amount (0, 10, and 30 wt %) and type of HA powder incorporated into an acrylic bone cement on the tensile properties, compression properties, and fracture toughness. The three different types of HA powders used were synthesized in the laboratory and coated with a silane agent prior to incorporation into the cement powder, and differed in particle size, water content, surface area, and crystallinity. It was found that the inclusion of any type of HA powder led to an increase in the tensile modulus (ET), but all the other mechanical properties of the cement decreased (relative to the values of the unfilled cement). The increase in ET is attributed to the good adhesion between the filler and the cement matrix, which is due to the silane coating agent. The decrease in the other mechanical properties may be a consequence of HA powder agglomeration and porosity. Hydroxyapatite morphology and crack-growth mechanisms were analyzed by scanning electronic microscopy (SEM).

Hydroxyapatites↗

Surgical glove powder and intraperitoneal adhesion formation. An appeal for the use of powder-free surgical gloves.

Intraperitoneal adhesion formation is a major cause of infertility and/or intestinal obstruction. Among the many well-known aetiological factors responsible for peritoneal inflammatory reaction is surgical glove powder; for example, cornstarch powder. A study was undertaken on 30 rats to determine whether cornstarch powder caused intraperitoneal adhesions. The rats were randomised into two groups under laboratory conditions. Laparotomies were performed on all the rats and trauma inflicted to the right uterine horn. The study group received cornstarch powder suspended in normal physiological salt solution intraperitoneally, and the control group received only normal physiological salt solution. Peritoneal adhesions were evaluated after 2 weeks and statistically analysed with a t-test and 95% confidence intervals. The study group showed a statistically significantly higher incidence of intraperitoneal adhesions (P = 0.0003). It is concluded that cornstarch, as used on surgical gloves, caused peritoneal adhesions and should therefore be removed before surgery. Powder-free gloves are more suitable for preventing adhesion formation.

Animals↗

Penetration of crystalline powder particles into excised human skin membranes and model gels from a supersonic powder injector.

The penetration of crystalline ibuprofen particles into excised human skin membranes and model target gels on actuation with the PowderJect ND1 ballistic needle-free injector has been examined. The deliverable dose of powder exiting the device is approximately 50% of the total cassette loading; the rest is lost via a gap forced open between the injector base and the surface of the target gel. It could be shown that substantial comminution of two different ibuprofen particle size fraction (38-53 microm, 53-75 microm) occurs within the injector on actuation. This resulted in an equiparation of the two initially different size fractions. Reduced comminution occurs with an ibuprofen/PVP (95:5) particulate formed by spray-drying/compaction/milling. On actuation into excised human skin membranes approximately 37% of cassette dose is recovered from the stratum corneum by stripping, and only 3% from the epidermis. It is concluded that powder delivery is mainly intra-epidermal with few particles fully breaching the stratum corneum. This is a consequence of the relative magnitude of the particle diameter (approximately 48 microm) and the stratum corneum thickness (approximately 10 microm). A 'soft' polyethylene glycol monolayer target gel gives the closest total percentage recovery of powder to that seen with the excised human skin membranes. Bilayer gels differentiated between surface impact/retention and penetration, but were difficult to handle. Powder penetration studies should therefore preferentially to be performed with human skin-membranes.

Administration, Cutaneous↗

Application of powder failure testing equipment in assessing effect on glidants on flowability of cohesive pharmaceutical powders.

Powder failure testing equipment was used successfully to study the effect of glidants on the flowability of two cohesive pharmaceutical powders, lactose and calcium hydrogen phosphate, using the flow factor as the flowability parameter. Fine silica, magnesium stearate, and purified talc were investigated as glidants; for each host powder-glidant mixture, an optimum concentration of glidant was observed beyond which no further increase in flowability occurred. The order of efficiency of glidants for both host powders was fine silica greater than magnesium stearate greater than purified talc. The mode of action of the three glidants is discussed.

Calcium Phosphates↗