Development of a simple method for the preparation of a silica gel based controlled delivery system with a high drug content.

Silica gel was used as core particles to design a simple preparation for controlled delivery system with a high drug content. Drug loading was carried out by immersing the silica gel in a pre-heated drug solution or suspension. HPLC, SEM, DSC, PXRD analysis and N2 adsorption studies evaluated the drug-loading process. In the next step, the drug-loaded silica gel was coated with hydroxypropyl methylcellulose (HPMC) and an aqueous dispersion of ethylcellulose (Aquacoat) to control the drug release. The release profile was determined using a dissolution test. The results showed that silica gel could adsorb great quantities of the drug, up to about 450 mg/g, by repetition of the loading process. Evaluation of the drug-loading process indicates that drug deposition in the pores occurs during the loading process and the drug-loading efficacy is strongly related to the drug solubility. On the other hand, the dissolution test showed that the drug release could be controlled by polymer coating the drug-loaded silica gel. An HPMC undercoating effectively suppresses the drug release, as it smoothes the drug-loaded core surface and aids in the formation of a continuous Aquacoat coating film. The floating property was also observed during the dissolution test.

Effect of geometric structure and surface wettability of glidant on tablet hardness.

The aim of this study is to investigate the effect of geometric structure and surface wettability of glidant on tablet hardness. Geometric structure is defined, in this work, as three-dimensional structure such as porosity, particle size and specific surface area. A variety of silica was incorporated in direct compressive fillers as glidant and mixed powder was compressed in single punch tablet machine with and without 0.5 wt.% magnesium stearate. Flowability of mixed powder was evaluated with Carr's index measurement. In the case of unlubricated compression, tablet hardness decreased as a function of additional concentration of silica. Reduction rate directly depended on surface coverage of silica over filler surface and hydrophobicity. Since surface coverage is related to geometric structure, it can be concluded that structural influence plays an important role to determine tablet hardness. While, in the case of lubricated compression, either water adsorption amount or geometric structure effects on tablet hardness. Increase of tablet hardness was observed only when hydrophilic porous and small size nonporous silica were added. All the other silica had deleterious effect on tablet hardness and in particular hydrophobicity strongly reduced tablet hardness.

Characterization of silica-pillared derivatives from aluminum-containing kanemite.

A series of aluminum-containing kanemite (Al-kanemite) samples with several Si/Al molar ratios were synthesized. The Al-kanemite samples were pillared with silica. X-ray diffractograms showed that the layered structure of the Al-kanemite samples was maintained at Si/Al= infinity approximately 10 but was broken at Si/Al = 5, 2.5, and 1. 29Si MAS NMR spectra of the Al-kanemite samples, except for that of Si/Al = 1, mainly showed peaks of Q(3) sites, which were attributed to Si(OSi)(3)(OH) groups, although peaks assigned to Si(OAl)(OSi)(2)(OH) were also seen. The 27Al MAS NMR spectra indicated that the Al-kanemite samples had only four-coordinate aluminum atoms. The FTIR spectra of pyridine adsorbed on the pillared Al-kanemite derivatives revealed Lewis acid sites on the surface. The nitrogen adsorption isotherms of the derivatives were classified as type I (Langmuir) absorption isotherms. Using the alpha(s) method, the specific surface areas of the derivatives were 572-756 m(2)g(-1), and the pore sizes were calculated as 1.25-1.83 nm. The pillared Al-kanemite derivatives had slit-shaped micropore structures.

Preparation and characterization of silica-pillared derivatives from kanemite.

The silica-pillared derivatives from kanemite (NaHSi(2)O(5).3H(2)O) were prepared by intercalation of dialkyldimethylammonium (DADMA) ion and pillaring with tetraethylorthosilicate. The formation of silica pillars between the silicate sheets was demonstrated by X-ray diffraction, (29)Si CP/MAS NMR, and TEM observation. The basal spacing depended on the chain length of DADMA. Nitrogen adsorption study showed that the specific surface area was enlarged over 1000 m(2) g(-1) by the pillaring and that the pore size was in the micropore region. Water and benzene adsorption isotherms revealed that the surface properties of the pillared derivatives show hydrophobic character.

Effect of geometric structure of flow promoting agents on the flow properties of pharmaceutical powder mixture.

PURPOSE: The object of this work was to investigate the mechanism of how the surface geometric structure of flow agents affects on the flowability of pharmaceutical powder mixtures. METHODS: Nonporous and porous silicas were mixed with directly compressible fillers as flow promoting agents. The geometric structure of flow agents was investigated by gas adsorption and laser diffraction analysis. Flowability was evaluated with Carr's index measurement. Adhesion force between fillers and flow agents was determined using atomic force microscopy. RESULTS: Flowability was improved with the addition of both nonporous and porous flow agents. In the case of nonporous flow agents, effect to promote flowability decreased with the increase of particle diameter, whereas porous flow agents highly improved flowability independent of particle diameter. Atomic force microscopy measurement found that the adhesion force between a porous agent and filler was smaller than that between a nonporous agent and filler. CONCLUSIONS: Enhancement of flowability varies depending on the geometric structure of flow agents. Porous flow agents improve flow properties more than nonporous agents, because porosity is highly contributed to reduction of adhesion force between particles.