Many bead biopharmaceutical characteristics are dependent on the bead shape. Furthermore, the shape is one of crucial parameters for incorporation of beads in more complex drug delivery system. Therefore, the aim of this study was to evaluate the influence of various processing parameters such as hardening time, temperature and concentration of calcium chloride solution and drying conditions on size, shape and morphology of alginate beads prepared by ionotropic gelation method. Theophylline was selected as a model drug. It was found that all studied parameters markedly affected bead form, resembling in most cases to ellipsoid spheres. Their sphericity was estimated three-dimensionally by measuring diameters of frontal and lateral side which were perpendicular to each other.Smaller and more spherical beads were obtained at longer hardening time and higher temperature of calcium chloride solution. The freeze-dried beads were the largest and the most spherical. It was demonstrated that optimization of bead shape as well as size and morphology could be achieved by altering processing parameters.

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The aim of this study was to investigate the characteristics of alginate beads prepared by ionotropic gelation in which structurally similar drugs were incorporated. For this purpose theophylline and theobromine were selected as model drugs. The influence of incorporated drugs on bead characteristics such as size, shape, and morphology, as well as encapsulation efficiency, was examined. It was found that theobromine as well as theophylline content in beads significantly decreased with increasing hardening time due to drug diffusion into the hardening media. In theobromine beads the drug content was extremely improved by dropping the alginate and drug solution into an acidic calcium chloride solution, while theophylline content was to some extent improved by the hardening of beads in a calcium chloride solution saturated with the drug. The most evident difference between theophylline and theobromine beads was in their shape and morphology. Theobromine beads were round, while theophylline ones had an irregular shape with an extremely wrinkled surface. The distinction in shape was highly dependent on drug content. Additionally, it was demonstrated that beads' shape was dependent on preparation conditions as well. On the basis of x-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analyses and scanning electron microscope (SEM) photographs it was found that the most of the drug in bead was present in an amorphous state. Therefore, it is suggested that some drug-alginate interactions could be present in beads and might be responsible for the different shape of theophylline and theobromine beads. Thus it can be concluded that the preparation of beads by ionotropic gelation cannot be generalized even though structurally similar drugs are incorporated.

LK-423 is hydrophilic, sparingly to slightly soluble, and poorly permeable. Stability profile in aqueous solution is pH dependent. A pharmacokinetic study following intravenous application to rats and dogs revealed that LK-423 is rapidly eliminated with a short terminal phase half-life, and high plasma clearance, as well as a limited distribution to the peripheral tissue. Oral bioavailability of LK-423 is low, presumably due to low permeability. Debris of insoluble microcapsule coating in feces and obtained plasma concentration profiles confirm that LK-423 microcapsules are a promising approach for local treatment of inflammatory diseases of the large intestine. Acute and a subchronic toxicity results indicate that LK-423 is a safe and nontoxic drug under the applied experimental conditions.

It is challenging to achieve mechanically robust drug-release profiles from hydrophilic matrices containing a high dose of a drug with good solubility. However, a mechanically robust drug release over prolonged period of time can be achieved, especially if the viscosity and amount of the polymer is sufficiently high, above the "threshold values." The goal of this research was to determine the hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) polymer threshold amount that would enable robust drug release from matrix tablets containing a high dose of levetiracetam as a class I model drug according to the Biopharmaceutical Classification System (BCS). For this purpose, formulations containing HPC or HPMC of similar viscosity range, but in different amounts, were prepared. Based on the dissolution results, two final formulations were selected for additional in vitro and in vivo evaluation to confirm the robustness and to show bioequivalence. Tablets were exposed to various stress conditions in vitro with the use of different mechanically stress-inducing dissolution methods. The in vitro results were compared with in vivo results obtained from fasted and fed bioequivalence studies. Under both conditions, the formulations were bioequivalent and food had a negligible influence on the pharmacokinetic parameters C max and area under the curve (AUC). It was concluded that the drug release from both selected formulations is mechanically robust and that HPC and HPMC polymers with intrinsic viscosities above 9 dL/g and in quantities above 30% enable good mechanical resistance, which ensures bioequivalence. In addition, HPC matrices were found to be more mechanically robust compared to HPMC.