Kalyana C. Pingali

Silver nanoparticles from ultrasonic spray pyrolysis of aqueous silver nitrate

Silver particles less than 20 nm in diameter were synthesized by pyrolysis of an ultrasonically atomized spray of highly dilute aqueous silver nitrate solution at temperatures above 650°C and below the melting point of silver. Feed solution concentration and ultrasound power applied to the atomizer were found to have a significant impact on the particle size of the silver nanoparticles. Average particle size was found to be controllable in the range of 20 nm to 300 nm by varying the solution concentration and the ultrasound power to the atomizer.

Mixing order of glidant and lubricant – Influence on powder and tablet properties

The main objective of the present work was to study the effect of mixing order of Cab-O-Sil (CS) and magnesium stearate (MgSt) and microlayers during mixing on blend and tablet properties. A first set of pharmaceutical blend containing Avicel PH200, Pharmatose and micronized acetaminophen was prepared with three mixing orders (mixing order-1: CS added first; mixing order-2: MgSt added first; mixing order-3: CS and MgSt added together). All the blends were subjected to a shear rate of 80 rpm and strain of 40, 160 and 640 revolutions in a controlled shear environment resulting in nine different blends. A second set of nine blends was prepared by replacing Avicel PH200 with Avicel PH102. A total of eighteen blends thus prepared were tested for powder hydrophobicity, powder flow, tablet weight, tablet hardness and tablet dissolution. Results indicated that powder hydrophobicity increased significantly for mixing order-1. Intermediate hydrophobic behavior was found for mixing order-3. Additionally, mixing order 1 resulted in improved powder flow properties, low weight variability, higher average tablet weight and slow drug release rates. Dissolution profiles obtained were found to be strongly dependent not only on the mixing order of flowing agents, but also on the strain and the resulting hydrophobicity.

Practical methods for improving flow properties of active pharmaceutical ingredients

Objective: The essential aim of this article is to develop effective methods for improving the flow properties of active pharmaceutical ingredients (APIs) without requiring particle size or shape modification. Methods: The ‘formulation’ approach used here focuses on enhancing flow properties of three chemically different drug powders (micronized acetaminophen, levalbuterol tartrate, and didesmethylsibutramine tartrate) by using small amounts of lubricants, glidants, and other additives, both individually and in combination. Additives are intimately mixed using a laboratory-scale V-blender with an intensifier bar. Flow index, dilation, and electrical impedance were measured for a total of 24 blends. Results: The flow behavior of all three APIs improved with the addition of these additives. Relative effectiveness of different additive combinations displayed remarkable consistency for all three APIs. Simultaneous presence of SiO2, MgSt, and talc led to substantial decreases in cohesiveness, causing major improvements in flowability of powder. All three properties showed a very tight correlation. Conclusions: Drug powders with improved flow were found to exhibit low dilation and low impedance values. A common linear correlation between flow index and impedance and also between dilation and impedance was observed for all three APIs, indicating that electric properties play a substantial role in the cohesivity of all three APIs, and suggesting the presence of a common mechanism for the emergence (and mitigation) of cohesive phenomena.

Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

Objective: The purpose of this study was to investigate the effect of mechanical shear on hydrophobicity of pharmaceutical powder blends as a function of composition and particle size, and to determine the impact on drug release from tablets. Methods: Four powder formulations were subjected to three different shear strain conditions (40 rev, 160 rev, and 640 rev) in a controlled shear environment operating at a shear rate of 80 rpm. A total of 12 blends were tested for hydrophobicity. Subsequently, sheared blends were compressed into tablets at 8 kN and 12 kN in a rotary tablet press. During tablet compression, powder samples were collected after the feed frame and their hydrophobicity was again measured. Results: Results indicated that increase in shear strain could significantly increase hydrophobicity, predominantly as an interacting function of blend composition. Blends with both colloidal silica and magnesium stearate (MgSt) were found to show higher hydrophobicity with shear than other blends. Additional shear applied by the tablet press feed frame was found to change the powder hydrophobicity only in the absence of MgSt. Conclusions: Studies showed that the drug release rates dropped with shear more for the blends with both colloidal silica and MgSt than the other blends. Furthermore, the rate of drug release dropped with a decrease in particle size of the main excipient. Surprisingly, the relationship between the relative increase in hydrophobicity and a corresponding drop in the drug release rate was not found when either MgSt or colloidal silica was mixed alone in the blends.

Synthesis of Ru-Ni Core-Shell Nanoparticles for Potential Sensor Applications

Nanoparticles of Ru-Ni with a core-and-shell structure were synthesized as potential sensors in a single-step spray-pyrolysis process at 700-1000. The majority of the core consists of ruthenium, while the shell is predominately composed of nickel. An aqueous precursor containing ruthenium chloride and nickel chloride was nebulized by an ultrasonic atomizer to generate an aerosol. The aerosol droplets were subsequently decomposed to form uniformly distributed Ru-Ni bimetallic nanoparticles. Atomic fractions of precursors, solvent type and process temperature play crucial roles in the formation of core-and-shell structures.

Direct Synthesis of Ru-Ni Nanoparticles with Core-and-Shell Structure

Nanoparticles of Ru-Ni with a core-and-shell structure were synthesized as potential catalysts for fuel cells and other applications in a single-step spray-pyrolysis process at 700°–800°C. The majority of the core consists of ruthenium, while the shell is predominately composed of nickel. Bimetallic nanoparticles with a core-and-shell structure are being considered as new and promising catalysts with enhanced catalytic activity, better stability, and higher resistance to contaminants for fuel cells and other applications. An aqueous precursor containing ruthenium chloride and nickel chloride was nebulized by an ultrasonic atomizer to generate an aerosol. Droplets were subsequently decomposed to form uniformly distributed Ru-Ni bimetallic nanoparticles, then deposited on a substrate. Atomic fractions and melting temperatures are expected to play a crucial role in the formation of core-and-shell structures.

Deposition of Ru-Ni-S Nanoparticles on Carbon by Spray-Pyrolysis: Effects of Solvent and other Processing Parameters

Nanoparticles of Ru-Ni-S were synthesized in a single-step spray-pyrolysis process as potential catalysts for fuel cells and other applications. The liquid precursors containing ruthenium, nickel, and sulfur were nebulized by an ultra-sonic atomizer to generate aerosol droplets, which were subsequently decomposed to form uniformly distributed nanoparticles for deposition on a carbon thin film. It was observed that the application of methanol as solvent has a strong effect on the particle morphology, size, and composition. The morphology of the Ru-Ni-S nanoparticles changed from spherical with water as solvent, to dendrites upon increase in the methanol con- centration in the precursor solution. It was also found that the pyrolysis temperature strongly affected the particle morphology when methanol was used as solvent. High temperatures promote dendrite formation. When a water/methanol mixture was used as solvent, crys- talline ternary nanoparticles of Ru-Ni-S on a carbon layer were formed at lower temperatures. A very interesting and unique structure of spherical clusters of crystalline particles attached by a chain of crystalline nanoparticles was synthesized. Elemental analysis obtained with EDS attached to the SEM used for particle characterization has confirmed the existence of all elements of interest, and X-ray map- ping showed all elements were distributed uniformly in the nanoparticles. Spray-pyrolysis processing is a versatile technique for produc- tion of inorganic materials of a wide range of composition, size, and morphology. It typically consists of several steps that may include: precursor preparation, precursor atomization, droplet evaporation, droplet precipitation, droplet drying, droplet coagulation, thermoly- sis, and sintering. An review on spray-pyrolysis processing by Messing et al. (1) has discussed the fundamental process parame- ters enabling the formation of particles with controlled morphology and composition. Among the important process parameters in spray-pyrolysis processing, the effects of precursor properties on particle size, composition, and morphology are probably the least understood. Synthesis of electrocatalysts in a spray-pyrolysis process for different types of fuel cells is a relatively new application of the spray-pyrolysis technique. Tolerance to small amounts of carbon monoxide and sulfur is important for proton exchange membrane fuel cells operating on hydrogen obtained by reforming carbon- based fuels. Conventional nanoparticles (2-5 nm) of platinum-based metal alloys are used as both anode and cathode catalysts for proton exchange membrane fuel cells due to the high activity for both hy- drogen oxidation and oxygen reduction (2). However the platinum- based catalysts used today suffer high polarization losses, reducing performance and fuel efficiency due to particle agglomeration, car- bon monoxide and sulfur poisoning (2, 3). The search for carbon monoxide and/or sulfur-tolerant non-platinum electrocatalysts for fuel cell applications have been a very active research endeavor (4- 10). Only a few researchers have studied the platinum- and ruthe- nium-based nanoparticles for methanol oxidation in fuel cell appli- cations. The binary and ternary crystalline nanoparticles were sup- ported on carbon nanofilm as fuel cell catalysts. Waszczuk et al. (11) studied the methanol adsorption on platinum-ruthenium sur- faces and observed that the decomposition of methanol is quite different at ultra-high vacuum. It was observed that the behavior of simple molecules would be different under ultra-high vacuum. Con- trol of size, morphology, and composition of nanoparticles is im- portant in the synthesis processing of ceramic powders. It was

Method to study the effect of blend flowability on the homogeneity of acetaminophen

Context: Excipient selection is key to product development because it affects their processability and physical properties, which ultimately affect the quality attributes of the pharmaceutical product. Objective: To study how the flowability of lubricated formulations affects acetaminophen (APAP) homogeneity. Materials and methods: The formulations studied here contain one of two types of cellulose (Avicel 102 or Ceollus KG-802), one of three grades of Mallinckrodt APAP (fine, semi-fine, or micronized), lactose (Fast-Flo) and magnesium stearate. These components are mixed in a 300-liter bin blender. Blend flowability is assessed with the Gravitational Displacement Rheometer. APAP homogeneity is assessed with off-line NIR. Results: Excluding blends dominated by segregation, there is a trend between APAP homogeneity and blend flow index. Blend flowability is affected by the type of microcrystalline cellulose and by the APAP grade. Conclusion: The preliminary results suggest that the methodology used in this paper is adequate to study of the effect of blend flow index on APAP homogeneity.

AFM study of hydrophilicity on acetaminophen crystals

Pharmaceutical powder processing is notoriously subject to unpredictable jamming, sticking and charging disturbances. To unveil the material science underlying these effects, we use atomic force microscopy (AFM) on a common pharmaceutical, acetaminophen (APAP). Specifically, we study surface adhesion and morphology as a function of relative humidity (RH) for monoclinic acetaminophen, using both plain AFM tips and tips functionalized to be hydrophobic or hydrophilic. Results indicate that the (001) crystal face exhibits significantly higher adhesion (surface potential) than the other crystal faces. For all the faces clear peaks in adhesion occur at 50-60% RH when they are examined using hydrophilic tips. The surface morphology of some facets showed a strong dependence on RH while others showed little or no significant change. In particular, the morphology of the (1-10) faces developed large terraces at high humidity, possibly due to deliquescence followed by recrystallization. These results confirm the hypothesis that different crystal facets exhibit distinct surface potentials and morphology that change with environmental exposure. The work suggests that future studies of powder behaviors would benefit from a more detailed modeling of crystal surface contact mechanics.

Effect of Ammonium Nitrate on Nanoparticle Size Reduction

Ammonium nitrate was added to the spraying solution as a foaming agent to reduce the particle size of nanoparticles synthesized in the spray-pyrolysis process. Ammonium nitrate was effective in breaking the aerosol droplet size and generating nanoparticles that were of approximately one order-of-magnitude (from 200 to 20 nm) smaller diameter than those created in the absence of ammonium nitrate in the feed solution. This technique makes it possible to control the particle diameter of metallic nanoparticles below 20 nm.