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The purpose of this research was to correlate the state of agglomeration determined by the modeling of dissolution and de-agglomeration profiles, using mixtures of micronised indomethacin designed to have different dissolution rates and extents of particle agglomeration in dissolution media. Dissolution profiles were determined using the USP paddle method. De-agglomeration profiles were obtained from laser diffraction particle sizing of mixtures of indomethacin in dissolution media under non-sink conditions. Data were modeled and key parameters estimated using a non-linear least squares estimation algorithm. The key parameters of initial apparent volume concentrations as dispersed and agglomerated particles, and dissolution rate constants (for dissolution modeling), and the apparent volume concentrations of dispersible and non-dispersible agglomerates and the de-agglomeration rate constant (for de-agglomeration modeling) were related to indomethacin and sodium lauryl sulphate concentrations in the lactose-povidone mixtures. Micronised sodium lauryl sulphate added to the mixture was more effective in de-agglomeration than equivalent concentrations in the dissolution media. An excellent correlation existed between the total initial apparent volume concentration of agglomerates determined by dissolution and de-agglomeration (P=0.98). The use of key parameters estimated from the modeling of dissolution and de-agglomeration profiles provides a useful tool in dosage form development of formulations of poorly water soluble drugs.

The objective of this research was to model benzodiazepine deagglomeration profiles of percent agglomerated versus time when interactive mixtures containing micronized benzodiazepines were added to water. Micronized diazepam, nitrazepam, oxazepam, and, for ternary mixtures, micronized sodium lauryl sulfate were mixed with lactose-povidone granules (250-355 microm). After rapid dissolution of the lactose granules, bimodal particle size distributions of benzodiazepines, determined by laser diffraction particle sizing, represented dispersed and agglomerated distributions. The concentrations of agglomerated particle decreased with time and approached constant values. Deagglomeration profiles were determined and best modeled by a three-parameter single-exponential decay equation. A nonlinear least-squares approach was used to estimate the concentration of dispersible (C(0)) and nondispersible agglomerates (C(0a)) and the deagglomeration rate constant (K(a)). Increasing benzodiazepine and sodium lauryl sulphate concentrations in the lactose-povidone mixtures increased both dispersible and nondispersible agglomerate concentrations. Deagglomeration rate was relatively fast with half-lives around 15 min. The estimated parameters of C(0a) and K(a) may provide useful information in optimizing the design of formulations of poorly water soluble, micronized drugs to maximize their dispersion.

The objective of this research was to develop a method to characterize the degree of particle agglomeration using laser diffraction particle sizing, following the addition of benzodiazepine interactive mixtures to water. Interactive mixtures of diazepam, nitrazepam and oxazepam (up to 20% w/w) were prepared by mixing micronized benzodiazepines with lactose granules (250–355μm). Micronized sodium lauryl sulfate and cetrimide (up to 5% w/w) were added to the benzodiazepine-lactose interactive mixes to produce ternary mixtures. Particle size distributions of benzodiazepines, after addition of the interactive mixtures to water, were determined using laser diffraction particle sizing. Bimodal distributions representing dispersed particles and agglomerates were observed initially after lactose carrier dissolution. Partial agglomerate to dispersed particle transition occurred during a 60-min observation period for all mixtures, reaching a constant level of agglomeration after this time. Interactive mixtures with higher benzodiazepine concentrations displayed transition profiles with higher levels of agglomeration. The presence of surfactant in interactive mixtures dramatically decreased agglomeration. Sodium lauryl sulfate was more effective than cetrimide in dispersing agglomerates. The shape of the transition curves during de-agglomeration demonstrated the presence of stable agglomerates that remained after the initial transition; these may be important in explaining dissolution and absorption rates.

Three compounds exist in the system Y2O3-Al2O3: Y4Al2O9, YAlO3, and Y3Al5O12 [1]. Y3Al5O12(YAG), and the most important of these compositions exists in the cubic form with a garnet structure. It is an important crystal for fluorescent and solid-state lasers, because it exhibits a thermally stable lattice, a well-determined crystal structure, and most importantly, resists saturation at high current excitation [2, 3]. Single crystals of Cr3+-doped YAG for example, are used in solid state lasers and Tb3+-doped YAG gives a characteristic narrow-band phosphor suitable for contrast-enhanced display applications [4, 5]. YAG phosphor powders are normally synthesized at relatively high temperatures by solid-state reaction between Y2O3 and Al2O3. Such conditions lead normally to powders of relatively large and varied grain sizes (5–20 μm) and varying impurity content. There are often problems in obtaining phase-pure material because of the intermediate formation of other phases, such as Y4Al2O9 and YAlO3 [6]. To achieve the desired phase purity and required particle size, high temperature treatment (>1600 ◦C) and extensive ball milling, which generally introduces additional impurities and defects and greatly reduces luminescence efficiency, are essential. For phosphor applications, it is desirable to have a fine particle size for high resolution and chemical purity for optimum chromaticity and brightness [7]. A few chemical synthesis techniques, such as sol-gel [8, 9], precipitation of hydroxides [10, 11], thermal decomposition of nitrates [12], hydrothermal treatment [13] and combus