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.

Is perception of upper body orientation based on the inertia tensor? Normogravity versus microgravity conditions

During lateral leg raising, a synergistic inclination of the supporting leg and trunk in the opposite direction to the leg movement is performed in order to preserve equilibrium. As first hypothesized by Pagano and Turvey (J Exp Psychol Hum Percept Perform, 1995, 21:1070-1087), the perception of limb orientation could be based on the orientation of the limb's inertia tensor. The purpose of this study was thus to explore whether the final upper body orientation (trunk inclination relative to vertical) depends on changes in the trunk inertia tensor. We imposed a loading condition, with total mass of 4 kg added to the subject's trunk in either a symmetrical or asymmetrical configuration. This changed the orientation of the trunk inertia tensor while keeping the total trunk mass constant. In order to separate any effects of the inertia tensor from the effects of gravitational torque, the experiment was carried out in normo- and microgravity. The results indicated that in normogravity the same final upper body orientation was maintained irrespective of the loading condition. In microgravity, regardless of loading conditions the same (but different from the normogravity) orientation of the upper body was achieved through different joint organizations: two joints (the hip and ankle joints of the supporting leg) in the asymmetrical loading condition, and one (hip) in the symmetrical loading condition. In order to determine whether the different orientations of the inertia tensor were perceived during the movement, the interjoint coordination was quantified by performing a principal components analysis (PCA) on the supporting and moving hips and on the supporting ankle joints. It was expected that different loading conditions would modify the principal component of the PCA. In normogravity, asymmetrical loading decreased the coupling between joints, while in microgravity a strong coupling was preserved whatever the loading condition. It was concluded that the trunk inertia tensor did not play a role during the lateral leg raising task because in spite of the absence of gravitational torque the final upper body orientation and the interjoint coupling were not influenced.

Use of physiotherapy and alternatives by children with cerebral palsy: a population study

Objectives: To describe the use of physiotherapy services and alternative therapies by a population of children with moderate to severe cerebral palsy (CP).
Design: Descriptive cross-sectional survey.
Subjects: A total of 212 parents of children aged 4–14 years with moderate to severe CP were identified from the Northern Ireland Cerebral Palsy Register (NICPR) and a random subsample of their paediatric physiotherapists.
Main measures: A standardized description of motor impairment or assessment form; a postal questionnaire to parents and paediatric physiotherapists (to validate parents’ reports of service use).
Response rates: In total, 85% of parent questionnaires were returned and 100% of paediatric physiotherapists responded.
Results: Service use among families was high; on average the families had contact with approximately seven services in a 6-month time interval. The overwhelming majority of children (96%) received physiotherapy during the school term and most (59%) received treatment at least twice a week for 30 min; 43% of children had their physiotherapy discontinued over the summer holidays. Over one-quarter (28%) of families had opted out of the NHS and bought alternatives like conductive education (21%) or private forms of conventional physiotherapy (16%). Children with more severe forms of CP, in special education, particularly at schools for physical disability, were high-intensity users of the physiotherapy service. Despite this, 74% of parents wanted more physiotherapy for their child.
Conclusions and implications: The demand for physiotherapy services is likely to continue given the relatively stable prevalence rate of CP, the proportion of children with disabling CP and the level of parent interest in the service. A number of quality aspects and gaps in the service have been identified.

Time operator for diffusion

Volume: 11 Issue: 4 Pages: 465-477 Published: MAR 2000 Times Cited: 9 References: 15 Citation MapCitation Map beta Abstract: We extend the concept of time operator for general semigroups and construct a non-self-adjoint time operator for the diffusion equation which is intertwined with the unilateral shift. We obtain the spectral resolution, the age eigenstates and a new shift representation of the solution of the diffusion equation. Based on previous work we obtain similarly a self-adjoint time operator for Relativistic Diffusion. (C) 2000 Elsevier Science Ltd. All rights reserved.