The formation of ring-banded spherulites of poly(epsilon-caprolactone) in its miscible mixtures with poly(styrene-co-acrylonitrile)

Ring-banded spherulites in polymer blends of poly(epsilon-caprolactone) (PCL) and poly(styrene-co-acrylonitrile) (SAN) were investigated by optical microscopy equipped with a digital image analysis system. PCL/SAN blends exhibit not only spherulites with a Maltese cross, but also distinct extinction rings. The periodic distance of rings changes with blend ratio and crystallization temperature and was plotted as a function of the undercooling and overall mobility of the mixtures, respectively. It was found that the overall mobility of chain segments in the mixtures could be mainly attributed to the origin of the formation of ring-banded spherulites. It was believed that for the first time a quantitative experimental result was obtained about the relationship of periodic distance of rings and the overall mobility of the mixtures. This relationship may be useful to explain the formation mechanism of ring-banded spherulites in polymer blends or even in homopolymers in the future. (C) 1977 Elsevier Science Ltd.

Miscibility and crystallization of poly(beta-hydroxybutyrate) and poly(p-vinylphenol) blends

The miscibility and crystallization behavior of poly(beta-hydroxybutyrate) (PHB) and poly(p-vinylphenol) (PVPh) blends were studied by differential scanning calorimetry and optical microscopy (OM). The blends exhibit a single composition-dependent glass transition temperature, characteristic of miscible systems, A depression of the equilibrium melting temperature of PHB is observed. The interaction parameter values obtained from analysis of the melting point depression are of large negative values, which suggests that PHB and PVPh blends are thermodynamically miscible in the melt. Isothermal crystallization kinetics in the miscible blend system PHB/PVPh was examined by OM. The presence of the amorphous PVPh component results in a reduction in the rate of spherulite growth of PHB. The spherulite growth rate is analyzed using the Lauritzen-Hoffman model, The isothermally crystallized blends of PHB/PVPh were examined by wide-angle X-ray diffraction and smell-angle X-ray scattering (SAXS). The long period obtained from SAXS increases with the increase in PVPh component, which implies that the amorphous PVPh is squeezed into the interlamallar region of PHB.

Synthesis of a series of chiral copolymers with azo groups and investigations of reversible liquid crystalline alignment induced by the LB films of these materials

A series of liquid crystalline copolymers, poly{2-hydroxyethyl methacrylate}-co-{6-[4-(S-2-methyl-1-butyloxycarbonylphenylazo)phenoxy]hexyl methacrylate} with an azobenzene moiety as photoreactive mesogenic unit, was prepared and investigated by using DSC, polarized optical microscopy and X-ray diffraction. The results show that these polymers exhibit smectic phases. Z-type Langmuir-Blodgett films of these copolymers were successfully deposited onto calcium fluoride and quartz. Reversible homeotropic and planar liquid crystal alignments were induced by using the photochromism of the LB films of one of the copolymers containing 20.6 mol % of the azo unit.

Epitaxial crystallization in the sPP/nylon-12 semicrystalline polymer system

The epitaxial crystallization behaviour of syndiotactic polypropylene (sPP) on highly oriented nylon-12 substrates has been investigated by means of transmission electron microscopy. The results obtained from bright field electron microscopy and electron diffraction indicate that sPP crystals grow epitaxially on the oriented nylon-12 substrate with their c-axes +/- 37 degrees apart from the chain axis of the nylon-12 substrate. The contact planes of the sPP crystals are the (100) lattice planes. Moreover, the epitaxial crystallization of nylon-12 on highly oriented sPP substrates from a dilute solution in cyclohexanone has also been studied using optical microscopy. The results show that the nylon-12 crystals grow epitaxially on the oriented sPP substrate with the oriented nylon-12 lamellae forming large, anisotropic domains. Copyright (C) 1996 Elsevier Science Ltd.

Synthesis of a new series of chiral Schiff's bases and their copper complexes

A new series of chiral Schiff's bases containing 2-hydroxybenzilideneaniline moieties and their copper complexes were synthesized and studied by differential scanning calorimetry, polarized optical microscopy, X-ray diffraction and EPR measurement. The results show that most of the Schiff's bases and only two of the copper complexes exhibited chiral smectic liquid crystal phases.

SYNTHESIS AND VARIABLE-TEMPERATURE FTIR STUDY OF 5 CHIRAL LIQUID-CRYSTALS INDUCED BY INTERMOLECULAR HYDROGEN-BONDING

Five new chiral liquid crystal systems induced by intermolecular hydrogen bonding between 4-[(S)-2-chloro-3-methyl]butyroyloxy-4'-stilbazole (MBSB, proton acceptor) and 4-alkoxybenzoic acids (nBA, proton donors) were prepared. Their liquid crystalline properties were investigated by DSC and polarized optical microscopy. Chiral nematic and chiral smectic phases were observed, and the thermal stability of one complex was studied through temperature dependent infrared spectroscopy.

SYNTHESIS AND PHASE-BEHAVIOR STUDIES OF 2 NEW CHIRAL LIQUID-CRYSTALS OF SCHIFF-BASE - THE INFLUENCE OF INTRAMOLECULAR HYDROGEN-BOND ON THE PHASE-BEHAVIOR

Two new chiral liquid crystals of schiff-base type have been synthesized. This series of compounds contain a-chloro acidic ester chain prepared from commercially available L-valine. Both of the compounds exhibit tilted smectic phases; their phase transitions were studied using DSC and polarized optical microscopy; the influence of intramolecular hydrogen bonds on the phase behavior was studied as well.

SYNTHESIS AND CHARACTERIZATION OF POLYACRYLATES CONTAINING CHARGE-TRANSFER GROUPS

Polyacrylates containing para-nitro azobenzene have been synthesized by free radical polymerization. The influence of the length of the spacer of the homopolyacrylates (HPn, n=3,4,6), content of methyl acrylate in the copolyacrylates (CP6) with para-nitro azobenzene groups on the thermal properties, such as liquid crystallinity, Tg and Tm, was studied by DSC, WAXD and polarized optical microscopy. Among the polymers studied, only the homopolyacrylate (HP6)with six carbon atoms in the spacer exhibited a nematic phase. The second-harmonic generation (SHG) signal of the poled HP6 film was detected qualitatively by Maker-fringer method.

ULTRASTRUCTURE OF LIQUID-CRYSTALLINE POLYACRYLATES CONTAINING P-NITRO AZOBENZENE

The phase behaviour ai the side chain liquid crystalline polyacrylates containing p-nitro azobenzene was studied bg DSC, WAXD and the polarized optical microscopy. It was shown that nematic phase can be formed for homopolymer HP6, no LC phase can be observed for HF3 and HP4; whereas smectic S-Ad phase can be obtained tor P-n when n was equal to 3,4, 6,8. The unique phase behaviour of the copolymers P-n was due to the existence of H bond between -COOH and -NO2 which lias been confirmed by FTIR. The molecular arrangement of the copolymers in their LC states was proposed from the results of WAXD and FTIR.

DYNAMIC SCALING AND FRACTAL BEHAVIOR OF SPINODAL PHASE-SEPARATION IN POLYMER MIXTURES OF POLY(METHYL METHACRYLATE) WITH POLY(STYRENE-CO-ACRYLONITRILE)

Dynamic scaling and fractal behaviour of spinodal phase separation is studied in a binary polymer mixture of poly(methyl methacrylate) (PMMA) and poly(styrene-co-acrylonitrile) (SAN). In the later stages of spinodal phase separation, a simple dynamic scaling law was found for the scattering function S(q,t):S(q,t) approximately q(m)-3S approximately (q/q(m)). The possibility of using fractal theory to describe the complex morphology of spinodal phase separation is discussed. In phase separation, morphology exhibits strong self-similarity. The two-dimensional image obtained by optical microscopy can be analysed within the framework of fractal concepts. The results give a fractal dimension of 1.64. This implies that the fractal structure may be the reason for the dynamic scaling behaviour of the structure function.

THE RING-BANDED SPHERULITE STRUCTURE OF POLY(EPSILON-CAPROLACTONE) IN ITS MISCIBLE MIXTURES WITH POLY(STYRENE-CO-ACRYLONITRILE)

The structure of the PCL spherulite in poly(epsilon-caprolactone)/poly(styrene-co-acrylonitrile) (PCL/SAN) blends was investigated by optical microscopy and small angle light scattering. The spherulite structure with a Maltese cross has been observed in pure PCL. Similar PCL/SAN blends exhibited not only spherulites with a Maltese cross, but also distinct extinction rings. The H(v) light scattering pattern especially caused diffraction rings in PCL/SAN blends but not in pure PCL. The spherical symmetry of spherulite PCL becomes more incomplete and the twist of the lamella becomes more irregular with increasing SAN content. It is found that the spherulite structure of PCL/SAN blends is dependent on the crystallization temperature and the concentration of SAN in PCL/SAN blends.

两种超微细矿物粉体材料的制备及应用研究

Superfine mineral materials are mainly resulted from the pulverization of natural mineral resources, and are a type of new materials that can replace traditional materials and enjoy the most extensive application and the highest degree of consumption in the present day market. As a result, superfine mineral materials have a very broad and promising prospect in terms of market potential. Superfine pulverization technology is the only way for the in-depth processing of most of the traditional materials, and is also one of the major means for which mineral materials can realize their application. China is rich in natural resources such as heavy calcite, kaolin, wollastonite, etc., which enjoy a very wide market of application in paper making, rubber, plastics, painting, coating, medicine, environment-friendly recycle paper and fine chemical industries, for example. However, because the processing of these resources is generally at the low level, economic benefit and scale for the processing of these resources have not been realized to their full potential even up to now. Big difference in product indices and superfine processing equipment and technologies between China and advanced western countries still exists. Based on resource assessment and market potential analysis, an in-depth study was carried out in this paper about the superfine pulverization technology and superfine pulverized mineral materials from the point of mineralogical features, determination of processing technologies, analytical methods and applications, by utilizing a variety of modern analytical methods in mineralogy, superfine pulverization technology, macromolecular chemistry, material science and physical chemistry together with computer technology and so on. The focus was placed on the innovative study about the in-depth processing technology and the processing apparatus for kaolin and heavy calcite as well as the application of superfine products. The main contents and the major achievements of this study are listed as follows: 1. Superfine pulverization processing of mineral materials shall be integrated with the study of their crystal structures and chemical composition. And special attention shall be put on the post-processing technologies, rather than on the indices for particle size, of these materials, based on their fields of application. Both technical feasibility and economic feasibility shall be taken into account for the study about superfine pulverization technologies, since these two kinds of feasibilities serve as the premise for the industrialized application of superfine pulverized mineral materials. Based on this principle, preposed chemical treatment method, technology of synchronized superfine pulverization and gradation, processing technology and apparatus of integrated modification and depolymerization were utilized in this study, and narrow distribution in terms of particle size, good dispersibility, good application effects, low consumption as well as high effectiveness of superfine products were achieved in this study. Heavy calcite and kaolin are two kinds of superfine mineral materials that enjoy the highest consumption in the industry. Heavy calcite is mainly applied in paper making, coating and plastics industries, the hard kaolin in northern China is mainly used in macromolecular materials and chemical industries, while the soft kaolin in southern China is mainly used for paper making. On the other hand, superfine pulverized heavy calcite and kaolin can both be used as the functional additives to cement, a kind of material that enjoys the biggest consumption in the world. A variety of analytical methods and instruments such as transmission and scanning electron microscopy, X-ray diffraction analysis, infrared analysis, laser particle size analysis and so on were applied for the elucidation of the properties and the mechanisms for the functions of superfine mineral materials as used in plastics and high-performance cement. Detection of superfine mineral materials is closely related to the post-processing and application of these materials. Traditional detection and analytical methods for superfine mineral materials include optical microscopy, infrared spectral analysis and a series of microbeam techniques such as transmission and scanning electron microscopy, X-ray diffraction analysis, and so on. In addition to these traditional methods, super-weak luminescent photon detection technology of high precision, high sensitivity and high signal to noise ratio was also utilized by the author for the first time in the study of superfine mineral materials, in an attempt to explore a completely new method and means for the study of the characterization of superfine materials. The experimental results are really exciting! The innovation of this study is represented in the following aspects: 1. In this study, preposed chemical treatment method, technology of synchronized superfine pulverization and gradation, processing technology and apparatus of integrated modification and depolymerization were utilized in an innovative way, and narrow distribution in terms of particle size, good dispersibility, good application effects, low consumption as well as high effectiveness of superfine products were achieved in the industrialized production process*. Moreover, a new modification technology and related directions for producing the chemicals were invented, and the modification technology was even awarded a patent. 2. The detection technology of super-weak luminescent photon of high precision, high sensitivity and high signal to noise ratio was utilized for the first time in this study to explore the superfine mineral materials, and the experimental results can be compared with those acquired with scanning electron microscopy and has demonstrated its unique advantages. It can be expected that further study may possibly help to result in a completely new method and means for the characterization of superfine materials. 3. During the heating of kaolinite and its decomposition into pianlinite, the diffraction peaks disappear gradually. First comes the disappearance of the reflection of the basal plane (001), and then comes the slow disappearance of the (hkl) diffraction peaks. And this was first discovered during the experiments by the author, and it has never before reported by other scholars. 4. The first discovery of the functions that superfine mineral materials can be used as dispersants in plastics, and the first discovery of the comprehensive functions that superfine mineral materials can also be used as activators, water-reducing agents and aggregates in high-performance cement were made in this study, together with a detailed discussion. This study was jointly supported by two key grants from Guangdong Province for Scientific and Technological Research in the 10th Five-year Plan Period (1,200,000 yuan for Preparation technology, apparatus and post-processing research by using sub-micron superfine pulverization machinery method, and 300,000 yuan for Method and instruments for biological photon technology in the characterization of nanometer materials), and two grants from Guangdong Province for 100 projects for scientific and technological innovation (700,000 yuan for Pilot experimentation of superfine and modified heavy calcite used in paper-making, rubber and plastics industry, and 400,000 yuan for Study of superfine, modified wollastonite of large length-to-diameter ratio).

Highly sensitive surface enhanced Raman scattering (SERS) detection platforms formed by large area self-assembled Au nanorod arrays

This thesis explores a new method to fabricate SERS detection platforms formed by large area self-assembled Au nanorod arrays. For the fabrication of these new SERS platforms a new droplet deposition method for the self-assembly of Au nanorods was developed. The method, based in the controlled evaporation of organic suspensions of Au nanorods, was used for the fabrication of horizontal and vertical arrays of Au nanorods over large areas (100μm2). The fabricated nanorods arrays showed a high degree of order measured by SEM and optical microscopy over mm2 areas, but unfortunately they detached from the support when immersed in any analyte solutions. In order to improve adhesion of arrays to the support and clean off residual organic matter, we introduced an additional stamping process. The stamping process allows the immobilization of the arrays on different flexible and rigid substrates, whose feasibility as SERS platforms were tested satisfactory with the model molecule 4ABT. Following the feasibility study, the substrates were used for the detection of the food contaminant Crystal Violet and the drug analogue Benzocaine as examples of recognition of health menaces in real field applications.

Micro-Anatomical Quantitative Imaging Towards Enabling Automated Diagnosis of Thick Tissues at the Point of Care

Histopathology is the clinical standard for tissue diagnosis. However, histopathology has several limitations including that it requires tissue processing, which can take 30 minutes or more, and requires a highly trained pathologist to diagnose the tissue. Additionally, the diagnosis is qualitative, and the lack of quantitation leads to possible observer-specific diagnosis. Taken together, it is difficult to diagnose tissue at the point of care using histopathology.

Several clinical situations could benefit from more rapid and automated histological processing, which could reduce the time and the number of steps required between obtaining a fresh tissue specimen and rendering a diagnosis. For example, there is need for rapid detection of residual cancer on the surface of tumor resection specimens during excisional surgeries, which is known as intraoperative tumor margin assessment. Additionally, rapid assessment of biopsy specimens at the point-of-care could enable clinicians to confirm that a suspicious lesion is successfully sampled, thus preventing an unnecessary repeat biopsy procedure. Rapid and low cost histological processing could also be potentially useful in settings lacking the human resources and equipment necessary to perform standard histologic assessment. Lastly, automated interpretation of tissue samples could potentially reduce inter-observer error, particularly in the diagnosis of borderline lesions.

To address these needs, high quality microscopic images of the tissue must be obtained in rapid timeframes, in order for a pathologic assessment to be useful for guiding the intervention. Optical microscopy is a powerful technique to obtain high-resolution images of tissue morphology in real-time at the point of care, without the need for tissue processing. In particular, a number of groups have combined fluorescence microscopy with vital fluorescent stains to visualize micro-anatomical features of thick (i.e. unsectioned or unprocessed) tissue. However, robust methods for segmentation and quantitative analysis of heterogeneous images are essential to enable automated diagnosis. Thus, the goal of this work was to obtain high resolution imaging of tissue morphology through employing fluorescence microscopy and vital fluorescent stains and to develop a quantitative strategy to segment and quantify tissue features in heterogeneous images, such as nuclei and the surrounding stroma, which will enable automated diagnosis of thick tissues.

To achieve these goals, three specific aims were proposed. The first aim was to develop an image processing method that can differentiate nuclei from background tissue heterogeneity and enable automated diagnosis of thick tissue at the point of care. A computational technique called sparse component analysis (SCA) was adapted to isolate features of interest, such as nuclei, from the background. SCA has been used previously in the image processing community for image compression, enhancement, and restoration, but has never been applied to separate distinct tissue types in a heterogeneous image. In combination with a high resolution fluorescence microendoscope (HRME) and a contrast agent acriflavine, the utility of this technique was demonstrated through imaging preclinical sarcoma tumor margins. Acriflavine localizes to the nuclei of cells where it reversibly associates with RNA and DNA. Additionally, acriflavine shows some affinity for collagen and muscle. SCA was adapted to isolate acriflavine positive features or APFs (which correspond to RNA and DNA) from background tissue heterogeneity. The circle transform (CT) was applied to the SCA output to quantify the size and density of overlapping APFs. The sensitivity of the SCA+CT approach to variations in APF size, density and background heterogeneity was demonstrated through simulations. Specifically, SCA+CT achieved the lowest errors for higher contrast ratios and larger APF sizes. When applied to tissue images of excised sarcoma margins, SCA+CT correctly isolated APFs and showed consistently increased density in tumor and tumor + muscle images compared to images containing muscle. Next, variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was further tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. The results indicate that SCA+CT can accurately delineate APFs in heterogeneous tissue, which is essential to enable automated and rapid surveillance of tissue pathology.

Two primary challenges were identified in the work in aim 1. First, while SCA can be used to isolate features, such as APFs, from heterogeneous images, its performance is limited by the contrast between APFs and the background. Second, while it is feasible to create mosaics by scanning a sarcoma tumor bed in a mouse, which is on the order of 3-7 mm in any one dimension, it is not feasible to evaluate an entire human surgical margin. Thus, improvements to the microscopic imaging system were made to (1) improve image contrast through rejecting out-of-focus background fluorescence and to (2) increase the field of view (FOV) while maintaining the sub-cellular resolution needed for delineation of nuclei. To address these challenges, a technique called structured illumination microscopy (SIM) was employed in which the entire FOV is illuminated with a defined spatial pattern rather than scanning a focal spot, such as in confocal microscopy.

Thus, the second aim was to improve image contrast and increase the FOV through employing wide-field, non-contact structured illumination microscopy and optimize the segmentation algorithm for new imaging modality. Both image contrast and FOV were increased through the development of a wide-field fluorescence SIM system. Clear improvement in image contrast was seen in structured illumination images compared to uniform illumination images. Additionally, the FOV is over 13X larger than the fluorescence microendoscope used in aim 1. Initial segmentation results of SIM images revealed that SCA is unable to segment large numbers of APFs in the tumor images. Because the FOV of the SIM system is over 13X larger than the FOV of the fluorescence microendoscope, dense collections of APFs commonly seen in tumor images could no longer be sparsely represented, and the fundamental sparsity assumption associated with SCA was no longer met. Thus, an algorithm called maximally stable extremal regions (MSER) was investigated as an alternative approach for APF segmentation in SIM images. MSER was able to accurately segment large numbers of APFs in SIM images of tumor tissue. In addition to optimizing MSER for SIM image segmentation, an optimal frequency of the illumination pattern used in SIM was carefully selected because the image signal to noise ratio (SNR) is dependent on the grid frequency. A grid frequency of 31.7 mm-1 led to the highest SNR and lowest percent error associated with MSER segmentation.

Once MSER was optimized for SIM image segmentation and the optimal grid frequency was selected, a quantitative model was developed to diagnose mouse sarcoma tumor margins that were imaged ex vivo with SIM. Tumor margins were stained with acridine orange (AO) in aim 2 because AO was found to stain the sarcoma tissue more brightly than acriflavine. Both acriflavine and AO are intravital dyes, which have been shown to stain nuclei, skeletal muscle, and collagenous stroma. A tissue-type classification model was developed to differentiate localized regions (75x75 µm) of tumor from skeletal muscle and adipose tissue based on the MSER segmentation output. Specifically, a logistic regression model was used to classify each localized region. The logistic regression model yielded an output in terms of probability (0-100%) that tumor was located within each 75x75 µm region. The model performance was tested using a receiver operator characteristic (ROC) curve analysis that revealed 77% sensitivity and 81% specificity. For margin classification, the whole margin image was divided into localized regions and this tissue-type classification model was applied. In a subset of 6 margins (3 negative, 3 positive), it was shown that with a tumor probability threshold of 50%, 8% of all regions from negative margins exceeded this threshold, while over 17% of all regions exceeded the threshold in the positive margins. Thus, 8% of regions in negative margins were considered false positives. These false positive regions are likely due to the high density of APFs present in normal tissues, which clearly demonstrates a challenge in implementing this automatic algorithm based on AO staining alone.

Thus, the third aim was to improve the specificity of the diagnostic model through leveraging other sources of contrast. Modifications were made to the SIM system to enable fluorescence imaging at a variety of wavelengths. Specifically, the SIM system was modified to enabling imaging of red fluorescent protein (RFP) expressing sarcomas, which were used to delineate the location of tumor cells within each image. Initial analysis of AO stained panels confirmed that there was room for improvement in tumor detection, particularly in regards to false positive regions that were negative for RFP. One approach for improving the specificity of the diagnostic model was to investigate using a fluorophore that was more specific to staining tumor. Specifically, tetracycline was selected because it appeared to specifically stain freshly excised tumor tissue in a matter of minutes, and was non-toxic and stable in solution. Results indicated that tetracycline staining has promise for increasing the specificity of tumor detection in SIM images of a preclinical sarcoma model and further investigation is warranted.

In conclusion, this work presents the development of a combination of tools that is capable of automated segmentation and quantification of micro-anatomical images of thick tissue. When compared to the fluorescence microendoscope, wide-field multispectral fluorescence SIM imaging provided improved image contrast, a larger FOV with comparable resolution, and the ability to image a variety of fluorophores. MSER was an appropriate and rapid approach to segment dense collections of APFs from wide-field SIM images. Variables that reflect the morphology of the tissue, such as the density, size, and shape of nuclei and nucleoli, can be used to automatically diagnose SIM images. The clinical utility of SIM imaging and MSER segmentation to detect microscopic residual disease has been demonstrated by imaging excised preclinical sarcoma margins. Ultimately, this work demonstrates that fluorescence imaging of tissue micro-anatomy combined with a specialized algorithm for delineation and quantification of features is a means for rapid, non-destructive and automated detection of microscopic disease, which could improve cancer management in a variety of clinical scenarios.

An investigation into the structure and bioavailability of a-tocopherol dispersions in Gelucire 44/14

In this investigation we describe the preparation, physical characterisation and in vivo behaviour of solid dispersions of a liquid nutraceutical, ±-tocopherol, in Gelucire 44/14 with a view to establishing whether dispersion in this matrix may provide a means of formulating a liquid drug in a solid dosage form while also improving the oral bioavailability. Using Vitamin E Preparation USP as the source of ±-tocopherol, dispersions were prepared using a melt-fusion method with active loadings up to 50% (w/w) and characterised using differential scanning calorimetry and optical microscopy. Capsules containing 300 IU ±-tocopherol were manufactured and the absorption profiles compared to a commercial soft gelatin capsule preparation in healthy human volunteers. Confocal laser scanning microscopy (CLSM) studies were performed in order to elucidate the mechanism by which drug release may be occurring. Differential scanning calorimetry studies indicated that the presence of the active had a negligible effect on the melting profile of the carrier, indicating limited miscibility between the two components, a conclusion supported by the microscopy studies. Similarly, the dispersions were shown to exhibit a glass transition corresponding to the incorporated drug, indicating molecular cooperativity and hence phase separation from the lipid base. Despite the phase separation, it was noted that capsules stored for 18 months under ambient conditions showed no evidence of leakage. Bioavailability studies in six healthy male volunteers indicated that the Gelucire 44/14 formulation showed an approximately two-fold increase in total ±-tocopherol absorption compared to the commercial preparation. Confocal laser scanning microscopy studies indicated that, on contact with water, the dispersions formed two interfacial layers, from which the Gelucire 44/14 disperses in the liquid medium as small particles. Furthermore, evidence was obtained for the dispersed material becoming incorporated into the hydrated lipid. In conclusion, the dispersion of the liquid drug in Gelucire 44/14 appears to allow the dual advantages of the preparation of a solid formulation and improved bioavailability of this material.