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.

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.

Processing of pharmaceutical materials by electrospraying under reduced pressure.

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.

Rapid formulation screening with a Multipart Microscale Fluid bed Powder processor.

The aim of this study was to investigate early formulation screening in small scale with a miniaturized fluid bed device. Altogether eight different batches were granulated in a Multipart Microscale Fluid bed Powder processor (MMFP) with constant process conditions using electrostatic atomization. Atomization voltage and granulation liquid flow rate were kept constant. Acid acetylsalicylic was used as model active pharmaceutical ingredient (API), lactose monohydrate, microcrystalline cellulose and polyvinylpyrrolidone were used as excipients. Granule size distributions were measured with spatial filtering technique. Friability test was performed by spinning granules in the mixer with glass beads. Compressibility of the granules was evaluated by tableting and the breaking force of the tablets was measured. Multivariate analysis, namely partial least squares regression and multilinear regression were applied to the data. It was possible to generate granules of different compositions rapidly employing MMFP with electrostatic atomization fast and acquire reliable and logical results with only small amount of material. However, a major challenge was to find suitable analytical methods for such small batches.

Modifying drug release and tablet properties of starch acetate tablets by dry powder agglomeration.

In this study three model drugs (N-acetyl-D-glucosamine (NAG), anhydrous caffeine, and propranolol hydrochloride) were agglomerated with starch acetate (SA) by mixing the binary powders on a stainless steel (SS) plate. Agglomeration was induced by triboelectrification of the particles during mixing, and it was evaluated as a method to achieve controlled drug release rate. These agglomerates, mixed with different amounts of a disintegrant, were compressed into tablets whose dissolution characteristics were determined. Triboelectric measurements showed that when the drugs were in contact with SS, charges of the opposite polarity were generated to SA (+) and caffeine and NAG (-) promoting adhesion. Instead, propranolol HCl was charged with the same polarity as SA. SEM micrographs showed that smaller caffeine particles, in spite of their larger negative charge, agglomerated less efficiently with SA than larger NAG particles. This emphasizes the importance of particle size in the agglomeration process. Propranolol HCl did not form agglomerates with SA since their particle sizes and charges were identical. As a result, agglomeration of powders prior to tablet compression allows for modification and control of the release rate of the drugs from the SA matrix tablets as well as the tensile strength of the tablets.

Effect of particle morphology on the triboelectrification in dry powder inhalers.

Electrostatic charge of lactoses of different particle morphology and amorphous contents were measured during actuation from two different dry powder inhalers (DPIs). Triboelectric studies may give important information when new inhaler devices, materials and formulations are designed in order to improve the drug deposition. Two inhalers, Taifun (Focus Inhalation Oy, Finland) and Clickhaler (Innovata Biomed Ltd., UK) were filled with lactose powders which were spray dried from different solutions or suspensions of lactose, ethanol and water. Differences in the amorphous contents were determined with isothermal microcalorimetry (IMC) and X-ray diffraction (XRD) and the particle morphology was examined with laser diffraction and electron microscopy (SEM). Samples were actuated from the inhalers at given intervals into the Faraday pail and the generated charges were recorded. Increase in the water concentration of the feed suspension had negligible effect on the charging until it exceeded 70%. Reproducibility of the measurement was found to be better with samples of homogenous particles and higher crystallinity while more amorphous samples with different morphology and wide particle size distribution showed change in the sign of the charge in addition to higher variations of the magnitude. In this study we show that different inhalers, as well as the morphology of the lactose powder, has noticeable effects on the generated charge which has previously been shown to affect the deposition of the drug and the function of an inhaler.

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.