Preparation of Solifenacin Succinate Functional Particles Embedded in a Gelling-Swelling Layer (PEGS) and Their Formulation in Orally Disintegrating Tablets.

The purpose of this research was firstly to prepare solifenacin succinate functional particles embedded in a gelling-swelling layer (PEGS) so as to achieve both taste-masking of the unpleasant taste of the drug and rapid drug elution, and secondly to incorporate these PEGS into orally disintegrating tablets (ODTs). In in vitro dissolution tests, initial drug release from the prepared PEGS could be suppressed to less than 1% after 2 min and increased to more than 85% after 30 min by adjusting the composition of the PEGS, in particular the thickness of the outer water-penetration control layer which contains a water-insoluble polymer. For the preparation of ODTs containing PEGS, a semi-direct compression method was adopted in order to prevent damage to the PEGS by processes such as granulation or compaction.

Preparation of Novel Functional Drug Particles Embedded in a Gelling-Swelling Layer (PEGS) for Taste Masking and Subsequent Rapid Drug Release.

The purpose of this research was to develop novel functional drug particles embedded in a gelling-swelling layer (PEGS) which are capable of achieving both taste-masking of unpalatable drugs and rapid drug elution. The functional particles had a three-layer structure consisting of a core drug layer, a gelling-swelling layer and an outer water-penetration control layer containing a water-insoluble polymer. The concept of formulation design was as follows: when water reaches the gelling-swelling layer, pulverized fine gelling-swelling particles gellate and swell from water absorption to form a rigid layer, thereby preventing drug release.

Development of a novel and simple method to evaluate disintegration of rapidly disintegrating tablets.

The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g.

A completely solvent-free process for the improvement of erythritol compactibility.

Objective: We obtained improvement of erythritol compactibility by formulating composite particles composed of erythritol and porous silica using a twin-screw kneader.

Methods: Erythritol-based tablets formulated with composite particles were directly compacted, and we estimated their hardness and the friability. The compression properties of the erythritol powder bed including composite particles were estimated using a Heckel analysis and force-displacement profiles, and we investigated the physical states of the composite particles by powder X-ray diffractometry, a thermal analysis and a nitrogen gas adsorption study.

Solventless dry powder coating for sustained drug release using mechanochemical treatment based on the tri-component system of acetaminophen, carnauba wax and glidant.

Objective: Solventless dry powder coating methods have many advantages compared to solvent-based methods: they are more economical, simpler, safer, more environmentally friendly and easier to scale up. The purpose of this study was to investigate a highly effective dry powder coating method using the mechanofusion system, a mechanochemical treatment equipped with high compressive and shearing force.

Materials And Methods: Acetaminophen (AAP) and carnauba wax (CW) were selected as core particles of the model drug and coating material, respectively.

The C-helix in CooA rolls upon CO binding to ferrous heme.

CooA is a homodimeric transcriptional activator from Rhodospirillum rubrum containing one heme in each subunit. CO binding to the heme in its sensor domain activates CooA, facilitating the binding to DNA by its DNA-binding domain. The C-helix links the two domains and shapes an interface between the subunits.

Roles of heme axial ligands in the regulation of CO binding to CooA.

CooA is a CO-dependent transcription factor of the bacterium Rhodospirillum rubrum that contains a six-coordinate heme. It has as its heme axial ligands Pro(2) and Cys(75) in the ferric state and Pro(2) and His(77) in the ferrous state. To probe the regulation of CO binding and the ligand switching mechanism in CooA, we have prepared site-directed mutants in which the residues contributing the axial ligands are substituted.