Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films.

Changes in tensile properties and the glass transition temperature (Tg) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the Tg on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and Tg of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (Tg') well below (113 to 127 °C) the bulk Tg. The relaxation times (τ) were 71 ±â€¯1, 46 ±â€¯1, 42 ±â€¯1, 36 ±â€¯1 and 29 ±â€¯1 s for HPMC films containing 0, 6, 8, 11 and 17% (w/w) PEG, respectively. The Tg and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, Tg and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries.

Controlled release of microencapsulated docosahexaenoic acid (DHA) by spray-drying processing.

The omega-3-fatty acid, docosahexaenoic acid (DHA) 22:6 n-3, is an important food component for the visual and brain development of infants. In this study two approaches have been explored for the encapsulation of DHA in the pH dependant polymer hydroxyl-propyl-methyl-cellulose-acetate-succinate (HPMCAS). In the first approach Direct Spray Drying (DSD) was implemented for the microencapsulation of DHA/HPMCAS organic solutions, whilst in the second approach solid lipid nanoparticle (SLN) dispersions of DHA, were first produced by high-pressure homogenization, prior to being spray dried in HPMCAS aqueous solutions. The DSD approach resulted in significantly higher quantities of DHA being encapsulated, at 2.09 g/100 g compared to 0.60 g/100 g in the spray-dried SLNs. The DHA stability increased with the direct spray-drying approach. Release studies of DHA in the direct sprayed dried samples revealed a lag time for 2 h in acidic media followed by rapid release in phosphate buffer (pH 6.8).

Treating Childhood Malnutrition in Rural Haiti: Program Outcomes and Obstacles.

BACKGROUND: Haiti has the worst malnutrition rate in the Western hemisphere. In October 2010, a cholera epidemic erupted and spread rapidly throughout the country, straining Haiti's already fragile health infrastructure across all levels of care. This study reviews data from an outpatient therapeutic feeding program (OTP) for acute childhood malnutrition at a clinic in rural Haiti with a focus on the effect of the 2010 cholera epidemic on program operations. METHODS: A retrospective chart review was conducted for the complete set of patients who were enrolled in the OTP from its inception in March 2009 through January 2014. FINDINGS: A total of 187 charts were retrieved representing 176 unique patients, of whom 5 were currently enrolled in care. At admission, 96 (51.3%) met criteria for severe acute malnutrition, 88 (47.1%) met criteria for moderate acute malnutrition, and 3 (1.6%) did not meet criteria for acute malnutrition. Of the 182 completed charts, 119 (65.4%) reached their target weight (≥-1 weight-for-height z-score) by discharge (ie, were "cured"), 43 (23.6%) defaulted, 11 (6.0%) were discharged prematurely, 8 (4.4%) died, and 1 (0.5%) was hospitalized. A total of 11 patients (6.3%) who were initially admitted relapsed after discharge and were later readmitted. Data from 170 complete records (93.4%) were included in a multivariate logistic regression. Severe (vs moderate) acute malnutrition was negatively associated with likelihood of being cured when controlling for other patient- and care-related factors (OR = 0.261, P = .002). Average cholera burden was negatively correlated with likelihood of OTP treatment cure when controlling for patient- and care-related variables (OR = 0.859, P = .002) but was insignificant when controlling for year. CONCLUSIONS: Results from the study have been used to inform a restructuring of the clinic's acute malnutrition program toward a more community-centered model of management, the context and implications of which are discussed in relation to the existing literature.

Molecular mobility of hydroxyethyl cellulose (HEC) films characterised by thermally stimulated currents (TSC) spectroscopy.

Molecular mobility has long been established to relate to textural properties and stability of polymer films and is therefore an important property to characterise to better understand pharmaceutical film formulations. The molecular mobility of solvent cast hydroxyethyl cellulose (HEC) films has been investigated by means of thermally stimulated current (TSC) below the temperature at which the film was formed. Preliminary physical characterisation of the films was performed using XRPD, TGA, DSC and texture analysis (tensile properties). XRPD results showed the films to be completely amorphous with Tg determined by DSC to be 127 ± 1°C. TGA analysis showed the films to contain 8 ± 1% water and film was dried to only 0.06 ± 0.01% water content when heated to 160°C. Application of TSC detected molecular mobility in HEC films at sub-zero temperatures. Two motional transitions with average relaxation time of 50 ± 3s were identified; a ß-relaxation at -57 ± 2°C, attributed to localised non-cooperative orientation of HEC polymer chain ends and the hydroxyethyl side groups and an α-relaxation, originating from cooperative segmental mobility, at -20 ± 2°C. The tensile properties i.e., elongation, tensile strength and elastic modulus of the HEC film have been related to the molecular relaxation processes detected by TSC.

Triboelectrification and dissolution property enhancements of solid dispersions.

The use of solid dispersion techniques to modify physicochemical properties and improve solubility and dissolution rate may result in alteration to electrostatic properties of particles. Particle triboelectrification plays an important part in powder processing, affecting end product quality due to particle deposition and powder loss. This study investigates the use of glucosamine hydrochloride (GLU) in solid dispersions with indomethacin. Solvents selected for the preparation of the dispersions were acetone, acetone-water, ethanol and ethanol-water. Solid state characterizations (DSC, FTIR and XRPD) and dissolution were conducted. Dispersions were subjected to charge using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. All dispersions improved the dissolution rate of indomethacin. Analysis showed the method of preparation of the dispersion induced polymorphic forms of the drug. Indomethacin had a high propensity for charging (-411 nC/g). GLU had a very low charge (-1 nC/g). All dispersions had low charges (-1 to 14 nC/g). Acetone as a solvent, or in combination with water, produced samples with an electronegative charge in polarity. The same approach with ethanol produced electropositive charging. The results show the selection of solvents can influence powder charge thereby improving powder handling as well as dissolution properties.

Novel analytical approaches for the study of mobility and relaxation phenomena in positional isomers of GABA.

γ-Aminobutyric acid (GABA), and its positional isomers DL-α-aminobutyric acid (AABA) and DL-ß-aminobutyric acid (BABA) have been analysed, in the solid state, using thermally stimulated current (TSC) spectroscopy. Secondary relaxations in these molecules have been detected for the first time. GABA displays two secondary relaxations at 77 ± 2 °C and 114 ± 2 °C, whilst AABA and BABA each display a single secondary relaxation at 109 ± 1 °C and 104 ± 1 °C, respectively. Analysis (decoupling of molecular mobilities) of secondary relaxations using thermal windowing (TW) and relaxation map analysis (RMA) show that the dipole relaxation associated with secondary transitions observed for the aminobutyric acids requires activation energies of 189.9 ± 3.2 kJ mol(-1) (GABA), 142.4 ± 1.4 kJ mol(-1) (AABA) and 195.7 ± 0.8 kJ mol(-1) (BABA). However, the ΔH(≠) values observed were found to exhibit negligible deviations from the zero entropy line. This indicates that the relaxation processes are localised, non-cooperative rotational motions that have a negligible influence on entropy changes of detected molecular mobilities. Furthermore, RMA analysis revealed that AABA and BABA display compensation behaviour i.e., entropy and enthalpy are linearly related to each other, whereas GABA did not demonstrate such behaviour. The coordinates of the compensation point (compensation temperature (Tc) and the compensation relaxation time (τc)) were found to be 214 ± 6 °C and 0.051 ± 0.024 s, respectively for AABA and 153 ± 3 °C and 0.025 ± 0.011 s for BABA. For the molecules investigated the compensation points coincide with the starting temperature of the higher temperature thermal events i.e. sublimation, melt/decomposition, and indicate a correlation between secondary relaxation processes and the main thermal transitions, found via TGA and DSC studies.

Sirolimus encapsulated liposomes for cancer therapy: physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers.

Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.