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Abstract: Although other polyols have been described extensively as filler-binders in direct compaction of tablets, the polyol isomalt is rather unknown as pharmaceutical excipient, in spite of its description in all the main pharmacopoeias. In this paper the compaction properties of different types of ispomalt were studied. The types used were the standard product sieved isomalt, milled isomalt and two types of agglomerated isomalt with a different ratio between 6-O-α-d-glucopyranosyl-d-sorbitol (GPS) and 1-O-α-d-glucopyranosyl-d-mannitol dihydrate (GPM). Powder flow properties, specific surface area and densities of the different types were investigated. Compactibility was investigated by compression of the tablets on a compaction simulator, simulating the compression on high-speed tabletting machines. Lubricant sensitivity was measured by compressing unlubricated tablets and tablets lubricated with 1% magnesium stearate on an instrumented hydraulic press. Sieved isomalt had excellent flow properties but the compactibility was found to be poor whereas the lubricant sensitivity was high. Milling resulted in both a strong increase in compactibility as an effect of the higher surface area for bonding and a decrease in lubricant sensitivity as an effect of the higher surface area to be coated with magnesium stearate. However, the flow properties of milled isomalt were too bad for use as filler-binder in direct compaction. Just as could be expected, agglomeration of milled isomalt by fluid bed agglomeration improved flowability. The good compaction properties and the low lubricant sensitivity were maintained. This effect is caused by an early fragmentation of the agglomerated material during the compaction process, producing clean, lubricant-free particles and a high surface for bonding. The different GPS/GPM ratios of the agglomerated isomalt types studied had no significant effect on the compaction properties. [Copyright &y& Elsevier]

In this study the effect of different vessel wall materials on the granule size distributions obtained during high-shear granulation of different materials is investigated. The distributions obtained in glass and stainless steel vessels differ from those obtained in PMMA (polymethyl methacrylate) and PTFE (polytetrafluoroethylene) vessels. The high contact angle of PMMA forces all liquid immediately into the more easily wetted powder bed. In this vessel a fast liquid absorbing powder nucleates in the droplet controlled regime, leading to a narrow particle size distribution. In a vessel with a low contact angle (glass or stainless steel) a liquid layer can be formed on the wall surface. This liquid causes an inhomogeneous distribution of liquid over the powder bed; a broader granule size distribution is the result. With a powder that slowly absorbs liquid, local overwet areas can be created, resulting in large granules. This results in broader granule size distributions as well. In conclusion; the contact angle of the vessel material and the wetting rate of the powder used determine the granule growth process and the resulting granule size distribution. [Copyright &y& Elsevier]

Abstract: In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl–homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4weeks at 20°C and 55°C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55°C for at least 4weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ∼1.8μm implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation. [Copyright &y& Elsevier]