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. The use of a fibre-shaped microcrystalline cellulose with poor fluidity improved the content uniformity of the ODTs, as the crystal fibres became entangled with the PEGS and other additives. The use of spherical mannitol with a hollow structure produced by spray drying imparted relatively high hardness and rapid disintegration properties to the final ODTs containing PEGS, which were tableted using a low compression force. There was no significant difference in the drug-release profiles of the optimally formulated ODTs containing PEGS tableted at different compression forces. The ODTs containing PEGS maintained a drug-release lag time sufficient for taste-masking of solifenacin succinate.

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. After a defined lag time, the increased volume of the gelling-swelling layer breaks down the outer water-penetration control layer, leading to rapid drug release. In order to adapt this system for use in orally disintegrating tablets, PEGS were prepared at a size of about 250 µm using a fine particle-coating method. Ambroxol hydrochloride was used as a model drug for bitterness and the effects of different gelling-swelling agents and water-insoluble polymers on drug release characteristics from PEGS were examined. In in vitro dissolution tests, it was shown that the drug dissolution rate from PEGS could be suppressed to about 5% after 2 min and increased to more than 85% after 30 min by adjusting the composition and thickness of the outer layer. The PEGS expanded about 1.5-fold and the outer layer was ruptured after 5 min in water.

Kinetic study of the binding of triplex-forming oligonucleotides containing partial cationic modifications to double-stranded DNA.

Several triplex-forming oligonucleotides (TFOs) partially modified with 2'-O-(2-aminoethyl)- or 2'-O-(2-guanidinoethyl)-nucleotides were synthesized and their association rate constants (kon) with double-stranded DNA were estimated by UV spectrophotometry. Introduction of cationic modifications in the 5'-region of the TFOs significantly increased the kon values compared to that of natural TFO, while no enhancement in the rate of triplex DNA formation was observed when the modifications were in the middle and at the 3'-region. The kon value of a TFO with three adjacent cationic modifications at the 5'-region was found to be 3.4 times larger than that of a natural one. These results provide useful information for overcoming the inherent sluggishness of triplex DNA formation.