Matti Murtomaa

Electrostatic measurements on a miniaturized fluidized bed

In the pharmaceutical industry fluidization is often used in drying, coating and granulation processes. During fluidization powder particles contact other particles as well as the walls of the vessel and this leads to generation of electric charges. These charges may result in sparks, dust explosions, fires, reduced process efficiency and particle accumulation on the walls. However, the mechanism of the charging is not well understood. In this paper, an inductive method for charge generation measurement is presented. The system consists of an electrostatic ring probe, which allows charge scanning across the miniaturized fluidized bed without disturbing the fluidization process. The charge coupling from the system to the probe has been modelled and the experimental data have been simulated using an advanced field solving software. Experiments on lactose monohydrate, microcrystalline cellulose and glass beads have been performed and these results are presented.

Electrostatic measurements on lactose–glucose mixtures

Abstract This paper presents the results of an experimental study on electrostatic behavior of lactose and glucose which are commonly used in the pharmaceutical industry as additives. Resistivities and frictional charging of samples with different proportions of lactose and glucose were measured. Powder samples were charged by sliding them down into the Faradays cup via a pipe. Resistivity was found to follow a linear relationship with the concentration but the nature of frictional charging changed considerably when mixtures were charged instead of pure additives. Both pure additives charged positively when slid into the Faradays cup via a glass pipe but some mixtures became negatively charged due to powder–powder contacts within the flow and near the pipe surface.

Effect of amorphicity on the triboelectrification of lactose powder

Abstract This paper presents the results of an experimental study of the effect of amorphous content on the triboelectrification of lactose powder. Lactoses of various degrees of amorphicity were prepared by spray drying from water/ethanol suspension containing 15% w/w α-lactose monohydrate. These powder samples were then tribocharged by sliding them through a polypropylene pipe into a Faraday pail. Usually, it is quite impossible to determine very small values of amorphicities. However, surface amorphicity has a significant role on the properties of the materials including charging. Triboelectrification being a very surface sensitive phenomenon might be a useful tool in studying the amorphous surfaces. Generated charges were found to increase with the increasing amorphicity and amorphous contents

Effect of surface coverage of a glass pipe by small particles on the triboelectrification of glucose powder

Abstract This paper presents the results of an experimental study on the triboelectrification of glucose powder in a glass pipe, and the role of smaller particles of different material mixed with a main phase. Mixtures of different concentrations were charged by sliding them down into the Faraday cup via a glass pipe. The influence of sticking to the inner surface of the pipe was examined with a microscope equipped with camera and an image analysis program. Smaller particles at the pipe surface partly change the glucose–glass contacts to the glucose–adhered powder contacts and this has a significant effect on the sign and the amount of transferred charge. The relative coverage of the glass pipe by small particles can be used as a measure of the charging ability of an additive, and can also give information regarding the sufficient amount of additive which would lead to neutral charge.

Measurement of electrostatic charge of an aerosol using a grid-probe

Abstract This paper describes an electrostatic grid-probe which can be used to study the charge of an aerosol emitted from a dry powder inhaler (DPI). Electrostatic charge plays a significant role in the function of an inhaler, separation of the drug and additive particles, and drug deposition in the lungs. The measurement system consists of three conducting grids through which the charged aerosol passes. The outer ones are connected to earth and the one in the middle is connected to an electrometer and a PC. Charge inside the probe induces a potential to the middle grid which is recorded as a function of time. When the distance between the grids is relatively small, the probe gives information about the charge distribution as a function of time. Therefore, the probe can be used to study whether the drug and additive particles are emitted separately from the DPI and the charge levels of both compounds. Measurements have been performed using several example powders and mixtures. Results show that the probe can separate signals from the drug and additive particles. Care has to be taken in interpreting the signals due to particles colliding with the grid and exchanging charge with it. Results were also verified by separating the aerosol physically using a high electric field separator. Separated particles were identified optically and also by using a differential scanning calorimeter.

Solid state transformations in consequence of electrospraying – A novel polymorphic form of piroxicam

The aim of the research was to verify that electrospraying of piroxicam yielded a new polymorphic form of this drug. In the experiments, piroxicam was dissolved in chloroform and the solution was atomised electrostatically. Subsequently, the charged droplets were neutralised and dried. The solid drug particles were collected and analysed by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, high performance liquid chromatography, and infrared and Raman spectroscopy. The X-ray diffractogram measured for the electrosprayed piroxicam particles did not match with any of the known piroxicam crystal structures (Cambridge Crystallographic Data Centre). The variable temperature X-ray diffraction showed that the structure recrystallised completely into piroxicam polymorphic formI during heating. No degradation products or solvate removal was detected by high performance liquid chromatography and thermal analysis. The infrared and Raman spectra of the electrosprayed piroxicam were compared to those of formI, and some notable differences in the peak positions, shapes and intensities were detected. The results indicate that electrospraying leads to piroxicam crystallisation in a currently unknown polymorphic form.

Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and in Vitro Evaluation.

The oral bioavailability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bioavailability can be improved by enhancing the physicochemical properties of the drug (e.g., dissolution rate, permeation across the gastrointestinal tract). Other approach include shielding the drug from the gastric metabolism and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug, griseofulvin, was encapsulated as disordered solid dispersions into Eudragit L 100-55 enteric polymer micromatrix particles, which were produced by electrospraying. Similar micromatrix particles were also produced with griseofulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micromatrices. The in vitro drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micromatrix particles, were investigated. The micromatrix particles were found to be gastro-resistant, while at pH 6.8 the griseofulvin was released very rapidly in a fast-dissolving form. Compared to free griseofulvin, the permeability of encapsulated griseofulvin across the intestinal cell monolayers was greatly improved, particularly for the TOPSi-doped micromatrix particles. The griseofulvin solid dispersions were stable during storage for 6 months at accelerated conditions. Overall, the method developed here could prove to be a useful oral drug delivery solution for improving the bioavailability of poorly water-soluble or otherwise problematic drugs.

Microscale granulation in a fluid bed powder processor using electrostatic atomisation

The aim of this study was to use the electrostatic atomisation in miniaturised fluid bed granulation process and define the effect of process parameters. The process parameters included in the study were granulation liquid flow rate, atomisation voltage and binder concentration in the granulation liquid. Altogether 22 batches were granulated in Multichamber Microscale Fluid bed powder Processor (MMFP). Granule size distributions were measured with both sieves and image analyses. With these process conditions, the atomisation liquid flow rate had a strong positive correlation with the granule size. Increasing the atomisation voltage increased the granule size, which is contradictory with the expectations. The effect of the binder concentration remained unclear. Although it is challenging to model the fluid bed granulation process in micro-scale, multivariate methods such as principal component analysis (PCA) are helpful in studying the most important phenomena.

Effect of detergent on powder triboelectrification

Triboelectrification of pharmaceutical powders during processing and manufacture may cause adhesion/cohesion effects, reduce fill and dose uniformity, affect powder flow and packing behaviour and even obstruct the manufacturing of the product. This paper presents the results of an experimental study on the triboelectrification of microcrystalline cellulose in contact with stainless steel pipes washed with several different detergents. Detergents and their concentrations were chosen to be similar to typical industrial manufacturing stages. The adhesion of powder to the surface had a considerable effect on the triboelectrification process. Therefore, polystyrene spheres were also charged in a similar way and the results were compared with the powder charging results. The results clearly indicate that detergent contamination on the pipe surface has a considerable effect on the generated charge. The detergents and powders used could be arranged in a triboelectric series with only one exception.

Processing of pharmaceutical materials by electrospraying under reduced pressure

Abstract Context: Electrospraying was used in drug particle production. Objective: The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied. Materials and methods: A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed. Results: The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure. Discussion and conclusions: A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.