Saša Baumgartner

Optimisation of floating matrix tablets and evaluation of their gastric residence time

The present investigation concerns the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. The importance of the composition optimisation, the technological process development for the preparation of the floating tablets with a high dose of freely soluble drug and characterisation of those tablets (crushing force, floating properties in vitro and in vivo, drug release) was examined. Tablets containing hydroxypropyl methylcellulose (HPMC), drug and different additives were compressed. The investigation shows that tablet composition and mechanical strength have the greatest influence on the floating properties and drug release. With the incorporation of a gas-generating agent together with microcrystalline cellulose, besides optimum floating (floating lag time, 30 s; duration of floating, >8 h), the drug content was also increased. The drug release from those tablets was sufficiently sustained (more than 8 h) and non-Fickian transport of the drug from tablets was confirmed. Radiological evidence suggests that, that the formulated tablets did not adhere to the stomach mucus and that the mean gastric residence time was prolonged (>4 h).

Advantages of celecoxib nanosuspension formulation and transformation into tablets.

Drugs with low aqueous solubility and high permeability (BCS class II) present a high proportion of all drugs. This study examines the critical issues regarding engineering of a nanosuspension tailored to increase drug dissolution rate and its transformation into dry powder suitable for tabletting. Nanosuspensions of celecoxib, a selective COX-2 inhibitor with low water solubility, were produced by the emulsion-diffusion method using three different stabilizers (Tween) 80, PVP K-30 and SDS) and characterized by particle size analysis, dissolution testing, scanning electron microscopy imaging, differential scanning calorimetry and X-ray powder diffraction. Spray-dried nanosuspension was blended with microcrystalline cellulose, and compressed to tablets, and their tensile strength, porosity and elastic recovery of tablets were investigated. The selection of solvent and stabilizers is critical, firstly to achieve controlled crystallization and size, and secondly to increase the wettability of the hydrophobic drug. The crystalline nano-sized celecoxib alone or in tablets showed a dramatic increase of dissolution rate and extent compared to micronized. SEM images showed that the nanoparticle morphology was influenced by the choice of stabilizers. Celecoxib nanosuspension stabilized with PVP K-30 and SDS showed advantages over Tween 80 due to sticking of the dried product and unexpected changes observed on DSC curves. Markedly lower compaction forces are needed for nano-sized compared to micro-sized celecoxib to produce tablets of equal tensile strength.

Network structure of cellulose ethers used in pharmaceutical applications during swelling and at equilibrium.

AbstractPurpose. The purpose of this work was to investigate the swelling behavior of four cellulose ethers that differ in their type and degree of substitution and to elucidate the network structure of the swollen matrices under dynamic and equilibrium conditions. Methods. Dynamic vapor sorption was performed to assess the ability of polymer chains and water molecules to interact. Dynamic and equilibrium swelling studies were performed to calculate molecular parameters of swollen polymers using the Flory-Rehner theory. Results. We determined the volume-swelling ratio of the polymer matrices and observed that it was dependent on their hydrophilicity. We determined molecular parameters that characterize the swollen hydrogels of cellulose derivatives, such as the polymer volume fraction in the swollen state, υ2,S, the effective molecular weight of the polymer chain between physical entanglements,

Investigation of the state and dynamics of water in hydrogels of cellulose ethers by1H NMR spectroscopy

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A compressibility and compactibility study of real tableting mixtures: The impact of wet and dry granulation versus a direct tableting mixture

e, the number of repeating units between two entanglements, u, and the number of entanglements per chain, e. The

Interfacial rheology: An overview of measuring techniques and its role in dispersions and electrospinning

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