PubMed Health⌕ Search

Biomedical subjects

Peter J Stewart

Publications and source records attributed to Peter J Stewart.

8 recordsLinked to original sources
PubMed2005

Understanding agglomeration of indomethacin during the dissolution of micronised indomethacin mixtures through dissolution and de-agglomeration modeling approaches.

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.

Chemistry, Pharmaceutical↗
PubMed2004

Modeling the deagglomeration of micronized benzodiazepines from powder mixtures added to dissolution media.

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.

Benzodiazepines↗
PubMed2003

Influence of physico-chemical carrier properties on the in vitro aerosol deposition from interactive mixtures.

Interactive mixtures were prepared containing 5% (w/w) salbutamol sulfate using various lactose carrier systems, including sieved fractions and blended mixtures of coarse and fine particles. The solid state and powder properties of the lactose carriers were examined by laser diffraction, differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, vapor sorption gravimetry, rotating drum and atomic force microscopy. The in vitro aerosol deposition was determined using a twin-stage impinger with a Rotahaler at an airflow rate of 60l/min. The fine particle fraction (FPF) of salbutamol sulfate was determined using a validated HPLC assay. All samples were highly crystalline with minimal moisture sorption and the major phase in all samples was alpha-lactose monohydrate. Significant differences in FPF were observed using the various carrier systems. FPF increased with decreasing carrier d(50%) (r(2)=0.919) and increasing proportion of fine carrier particles (below 5 microm) (r(2)=0.841). Carriers consisting of very large proportions of fine particles showed low FPF and did not fit the correlation. The presence of coarse carrier particle fractions was essential to achieve maximum FPF, which occurred when about 10% of fine carrier particles were present in the mixture. Dispersion characteristics may be related to the degree of drug aggregation on the carrier surface.

Aerosols↗
PubMed2003

De-agglomeration of micronized benzodiazepines in dissolution media measured by laser diffraction particle sizing.

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 (250-355 microm). 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.

Benzodiazepines↗
PubMed2002

Particle interactions involved in aerosol dispersion of ternary interactive mixtures.

PURPOSE: To investigate the mechanism of action of ternary components within dry powder aerosols. METHODS: Ternary interactive mixtures were prepared containing salbutamol sulphate (SS), coarse lactose carriers and either micronized lactose (ML) or micronized glucose (MG). In vitro drug and excipient aerosol deposition was performed using a twin-stage impinger (TSI) at 60 L/min with a Rotahaler device. Adhesional properties of the lactose carrier were examined using an atomic force microscope (AFM) colloidal probe technique. RESULT: The fine particle fraction (FPF) from ternary mixtures were dependent upon carrier type (p < 0.001), ternary concentration (p < 0.001) and ternary component type (p < 0.05). Ternary mixtures produced higher FPF than binary mixtures, except those containing Superfine (SF), which was attributed to the high proportion of intrinsic fine carrier particles. The higher FPF obtained from ternary mixtures was independent of the mixing order (p = 0.08). Increased adhesion force was observed on the carrier surface following the addition of ternary components (p < 0.001). CONCLUSION: The results confirm that ternary components increase aerosol deposition of powder mixtures. Some results were not entirely consistent with the saturation of active site theory and a hypothesis involving competitive and multilayer adhesion was proposed and requires further testing.

Aerosols↗
PubMed2002

The influence of aggregate microenvironment on the dissolution of oxazepam in ternary surfactant interactive mixtures.

The purpose of this research was to test the hypothesis that the dissolution rate of oxazepam in interactive mixtures was dependent on the influence of surfactant within the microenvironment of mixed oxazepam-surfactant aggegrates produced during dissolution. The studies utilised both powder and intrinsic dissolution methodology; spectrophotometric assays were developed and validated and dissolution data were modelled using multi-exponential equations and dissolution rate constants estimated using non-linear least squares algorithms. For a series of water-soluble ternary additives to the oxazepam interactive mixture, sodium lauryl sulfate and cetrimide were shown not only to decrease aggregation through enhanced dispersion, but also to increase the dissolution rate constant. Such an increase in dissolution rate constant was observed in the intrinsic dissolution studies when surfactant concentrations exceeded the critical micelle concentration and the oxazepam solubility increased. Laser diffraction particle sizing during the dissolution process confirmed the presence of dispersed particles and aggregates and demonstrated that the presence of surfactant improved the state of dispersion. The results of studies using different rotational speeds produced unexpected increases in aggregation and decreases in dissolution rate constants at about 150 rev min(-1), consistent with the transient formation of loose aggregates containing dissolved surfactant.

Linear Models↗