Modified drug release from inert matrix tablets prepared from formulations of identical composition but different organisations.

This paper develops for the first time a concept to modify the release rate of a fixed formulation by changing only the organisation of the mix used to prepare the tablets (ordered mixing). To estimate the influence of the organisation of binary mixes, several mixes of ethylcellulose and niflumic acid of the same composition but different organisation were compacted. The tablet surfaces were examined by energy dispersive X-ray microanalysis before the release experiments. Finally, the cross-sections of the remaining matrix were examined by scanning electronic microscopy. Excipient-excipient and excipient-drug interactions are the major factors influencing the drug release rate from the tablets. In the case of interacting materials, the initial release behaviour depends on the tablet surface presented to the dissolution media. The dissolution properties of the tablets are governed by the percolating material. When the inert excipient is percolating, the release rate increases linearly with the excipient/drug size ratio, whereas when the drug is the only material percolating through the system, its release rate is independent of the size ratio. When both materials are percolating through the system, the release rate is independent of the component particle sizes.

Color as an indicator of the organization and compactibility of binary powder mixes.

The aim of this study was to relate the color of several binary mixes to their organization as observed by scanning electronic microscopy, and to their compactibility. Binary mixes of niflumic acid (yellow) with ethyl cellulose, hydroxypropylmethylcellulose, low-substituted hydroxypropylcellulose (L-HPC), and ibuprofen (all white) were prepared using different particle size ranges. Colors of the mixes were determined by diffuse reflectance spectroscopy using a chromameter. Linear correlation was observed between the yellowness index/whiteness index ratio (Y/W ratio) defined by the American Society for Testing and Materials (ASTM) standards and the mean particle size difference of the materials which governs the organization of the blend. Except for the least interacting mix, the niflumic acid/L-HPC series, the color of the blend was also related to the tensile strength of the tablets made from the binary mixes. Color could be an interesting indicator of the organization of a powder mix. Diffuse reflectance spectroscopy could be used as a quality control tool because any modification of the color of the mix may be an indicator of a modification of its compactibility.

Recovery of human skin impedance in vivo after iontophoresis: effect of metal ions.

The objective of this study was to investigate the effect of the counter-ion (cation) on the recovery of human skin impedance after iontophoresis in vivo. A series of metal chloride aqueous solutions (NaCl, KCl, CaCl2, and MgCl2) was investigated: first at the same concentration (133 mmol/L) and then at the same ionic strength as a NaCl solution at 133 mmol/L. The influence of hydration alone was also examined as a control. The recovery of human skin impedance was followed in the frequency range 1-1,000 Hz, over a 30-minute period after iontophoresis during which 3 impedance spectra were recorded. The results revealed that at t = 30 minutes post-iontophoresis, skin impedance was approximately 3 times greater than the value immediately after the cessation of current passage. However, the results showed that the nature of the cation had no effect on recovery, regardless of whether the ions were at the same concentration or at an equivalent ionic strength. A simple parallel RC-equivalent circuit model for skin was used to determine the resistive (R) and capacitive (C) contributions to skin impedance. An analysis of variance on the calculated R and C values did not show any differences between the electrolytes used at the 2 different ionic strengths.

Influence of the organization of binary mixes on their compactibility.

PURPOSE: Elucidate the compactibility of binary mixes from their organization as compared to the traditional approach involving the different behavior of the materials under compression (plastic or brittle). METHODS: Several materials were selected from their surface energies. Binary mixes 50/50 v/v were prepared from different sieved or freeze-milled fractions. The tensile strengths of the tablets obtained at two compression forces were compared with those of series of compacted binary mixes containing different proportions of the raw materials (concept of equivalent media). RESULTS: In the case of interacting mixes, when the differences in particle size between the fractions blended increased, the material with the lowest particle size coated the largest particles more efficiently. Consequently, the tensile strengths of the tablets obtained became closer to the tensile strengths obtained from the pure coating material. For the non-interacting systems, the experimental tensile strengths were very close to the values calculated from the tensile strengths of the pure materials. CONCLUSIONS: This study clearly demonstrates the influence of the organization of binary mixes on their compactibility. The adhering material makes a percolating network governing the tensile strength of the tablet. From an industrial point of view, it is possible to improve the compactibility of binary mixes without changing their composition by selecting the appropriate organization.

Can the organization of a binary mix be predicted from the surface energy, cohesion parameter and particle size of its components?

PURPOSE: The aim of this study was to relate the organization of several binary mixes with three physical parameters (surface energy, cohesion parameter, and particle size) of various materials blended with each other. METHODS: Four pharmaceutical compounds were selected for their surface energies and cohesion parameters. Binary mixes were prepared from different sieved fractions. The frequency and nature of the interactions between the particles were observed by scanning electron microscopy. RESULTS: As expected, interactions were determined by both the energetics and the relative particle size of the two compounds blended, the latter determining the mode of interaction. However, particle size was not the only factor influencing the organization of the blends as, sometimes, small particles of a material would not adhere to the coarser particles of the other. Thus, a surface energy derived parameter ¿(B/A)lambda - (A/B)lambda¿ appears to be a valuable estimating tool of the potentiality of interaction between the particles blended. No correlation between the cohesion parameters of the compounds and the organization of the resulting blends could be found. CONCLUSIONS: Surface energy and particle size play a major role in the organization of a binary blend. However, they cannot explain separately the interactions observed between the fractions blended as reliable predictions require the use of both characteristics.