Influence of hydration state and homologue composition of magnesium stearate on the physical chemical properties of liquid paraffin lipogels.

Lipogels were prepared by dispersing mixed (60:40 C(16)-C(18)) and pure (C(18)) homologue magnesium stearate (MgSt) in liquid paraffin, using three methods of preparation, i.e. addition of water at 95 °C during cooling cycle (method 1), homogenisation upon cooling (method 2) or cooling without addition of water or homogenisation (method 3). The systems were characterised by physical inspection, polarised, hot stage and scanning electron microscopy (SEM), differential scanning calorimetry (DSC), rheology, and X-ray diffraction (XRD). Systems formed stable semisolid lipogels (no syneresis), unstable solids showing syneresis or structured fluids, depending on the type of magnesium stearate used and the preparation technique. The stable semisolid lipogels containing mixed homologue MgSt (commercial-as received, anhydrous or dihydrate) prepared by methods 1 (∼ 1-2% water) and 2 contained α-crystalline lamellar structure. These were not present in the unstable solids formed with method 3 or in systems prepared from pure homologue MgSt which were generally structured fluids rather than semisolids. In addition, semisolid lipogels of pure homologue trihydrate MgSt prepared by method 3 showed plate-like crystals, implying pressure sensitivity. There is significantly more amorphous MgSt in the unstable solids compared to the stable semisolid lipogels, which are mainly crystalline (confirmed by XRD).

Physical ageing and thermal analysis of PLGA microspheres encapsulating protein or DNA.

PLGA microspheres undergo physical ageing but their ageing kinetics have not been reported, nor the effect of encapsulated protein or plasmid DNA on any associated changes to the glass transition. Differential scanning calorimetry (DSC) was used to measure the rate of ageing of various PLGA microsphere formulations, with temperature-modulated DSC used to accurately measure the associated glass transition. The Cowie-Ferguson model was applied to determine the parameters describing the enthalpy relaxation kinetics. We show that encapsulated proteins had no significant effect on the glass transition of the microspheres, whereas DNA and PVA were mild antiplasticising agents, particularly with high Mw PLGA. Physical ageing occurred through a range of enthalpy relaxation times (or modes) and was independent of both encapsulated protein and surfactant used during microsphere preparation. Analysis of accelerated ageing at 35 degrees C gave calculated enthalpy relaxation times to thermal equilibrium of 280-400 h. No ageing was observed < or = 10 degrees C and at 25 degrees C estimated relaxation times were at least one order of magnitude greater than at 35 degrees C. Ageing of PLGA microspheres therefore occurs at temperatures >10 degrees C, but relaxation will be far from equilibrium unless storage times and/or temperatures are prolonged or nearing the glass transition, respectively.

Controlled drug delivery to the lung: Influence of hyaluronic acid solution conformation on its adsorption to hydrophobic drug particles.

This work reports investigations into the interaction and adsorption of the hydrophilic polymer hyaluronic acid (HA) onto the surface of the hydrophobic corticosteroid drug fluticasone propionate (FP). The eventual aim is to formulate a bioadhesive pulmonary drug delivery system with prolonged action that avoids rapid clearance from the lungs by the mucociliary escalator. Adsorption isotherms detailing the adsorption of HA from aqueous HA solution concentrations ranging from 0.14 to 0.0008% (w/v) to a fixed FP particle concentration of 0.1% (w/v) were investigated. The method of preparing FP particles with HA molecules adsorbed on their surfaces (FP/HA particles) involved suspension of the FP either in hydrated HA solution or in water followed by addition of solid HA, centrifugation of the solids to form a pellet, washing the pellet several times with water until no HA was found in the supernatant and then freeze drying the suspension obtained by dispersing the final pellet. The freeze dried powder was then analysed for adsorbed HA using a Stains-all assay. The influence of order of addition of HA to FP, time for the adsorption process, and temperature of preparation on the adsorption isotherms was investigated. The non-equilibrium adsorption isotherms produced generally followed the same trend, in that as the HA solution concentration increased, the amount of HA adsorbed increased to a maximum at a solution concentration of approximately 0.1% (w/v) and then decreased. The maxima in the adsorption isotherms were close to the change from secondary to tertiary conformation in the HA solutions. Below the maxima, adsorption occurred via interaction of FP with the hydrophobic patches along the HA chains in the secondary structures. Above the maxima, secondary HA molecules aggregate in solution to form tertiary network structures. Adsorption from tertiary structure was reduced because strong interactions between the HA molecules limited the availability of hydrophobic patches for adsorption of HA onto FP. The influence of preparation variables on adsorption was also related to the availability of hydrophobic patches for adsorption.

The influence of surfactant on PLGA microsphere glass transition and water sorption: remodeling the surface morphology to attenuate the burst release.

PURPOSE: The stability of protein unloaded and loaded poly(lactic-co-glycolic acid) (PLGA) microspheres fabricated with surfactant was challenged through exposure to environmental conditions of different relative humidity. METHODS: Polyvinyl alcohol (PVA) or Triton X-100 was added to the primary emulsion of the double-emulsion solvent evaporation technique. After storage at ambient humidity and 75% relative humidity, the mechanical stability of the polymer was tested to reveal PLGA chain mobility using differential scanning calorimetry. Subsequent surface modifications were examined by atomic force microscopy (AFM), and protein release profiles were collected. RESULTS: Residual amounts of PVA and particularly Triton X-100 raised the hydrophilicity of the microspheres. When exposed to ambient humidity or 75% relative humidity, PVA and Triton X-100 had, respectively, an antiplasticizing and a plasticizing effect upon PLGA, and both led to physical aging. The high-resolution AFM imaging of microspheres containing model protein and Triton X-100 showed that the depth of the surface pores was reduced when exposed to 75% relative humidity, and the initial burst release subsequently decreased. CONCLUSION: These studies suggested that the mechanical stability of PLGA was influenced by the addition of surfactants, which, depending on the formulation, led to surface pore remodeling under high humidity, reducing the initial burst release while maintaining the spherical integrity of the microsphere.

Evaluation research on prison-based drug treatment programs and some policy implications.

Prison-based drug treatment programs in the United States have been in existence for over 20 years. However, it is only in the last few years that they have been available on a large scale. The effects of these programs on recidivism rates tend to be mixed. Given the relatively modest costs, prison administrators may feel the costs are justified even when marginal results are obtained.

Agglutination of Erwinia stewartii Strains with a Corn Agglutinin: Correlation with Extracellular Polysaccharide Production and Pathogenicity.

A bacterial agglutinin was extracted from ground corn (WI hybrid 64A x W117) seed with phosphate-buffered saline (pH 6.0) and precipitated with (NH(4))(2)SO(4) at 70% saturation. The activities of this agglutinin against 22 strains of Erwinia stewartii (agent of bacterial wilt of corn) that varied in virulence were determined. Specific agglutination (agglutination titer per milligram of protein per milliliter) values were correlated negatively with virulence ratings. Strains with high specific agglutination values (15 or higher) were avirulent or weakly virulent; strains with low specific agglutination values (10 or lower) were highly virulent, with two exceptions. Avirulent strains produced butyrous colonies and released only small amounts of extracellular polysaccharide (EPS) into the medium, and the cells lacked capsules; virulent strains produced fluidal colonies and released large amounts of EPS, and the cells were capsulated. There was a strong correlation between the amount of EPS produced by each strain (as determined by increase in viscosity of the medium) and the specific agglutination value; in contrast, lipopolysaccharide compositions were similar in all strains. When cells of six fluidal strains were washed by repeatedly centrifuging and resuspending them in buffer, they were agglutinated more strongly by corn agglutinin than were unwashed cells. When avirulent cells were washed, their specific agglutination values did not increase significantly. Eight EPS-deficient mutants of E. stewartii, selected for resistance to the capsule-dependent bacteriophage K9, had lower virulence but higher specific agglutination than did their corresponding wild-type parents. Production of EPS appears to be essential for virulence; EPS may prevent agglutination of bacteria in the host, thus allowing their multiplication.