Mark Christie

Duel-Acting Subcutaneous Microemulsion Formulation for Improved Migraine Treatment with Zolmitriptan and Diclofenac: Formulation and In Vitro-In Vivo Characterization

Subcutaneous triptan provides immediate analgesia in migraine and cluster headache but is limited by high pain recurrence due to rapid drug elimination. A dual-acting subcutaneous formulation providing immediate release of a triptan and slow but sustained release of a nonsteroidal anti-inflammatory drug may provide a longer duration of relief. A microemulsion-based technology has various advantages over other technically complex dosage forms. Oil-in-water microemulsions of zolmitriptan and diclofenac acid using Labrafac Lipophile, Tween 80, Capryol 90 and water were prepared. One formulation was characterised in vitro and found to have uniformly dispersed nanosized globules. The formulation provided differential release of zolmitriptan and diclofenac acid both in vitro as well as in vivo that may be potentially beneficial to migraine patients.

Beyond HRV: attractor reconstruction using the entire cardiovascular waveform data for novel feature extraction

Abstract Advances in monitoring technology allow blood pressure waveforms to be collected at sampling frequencies of 250–1000 Hz for long time periods. However, much of the raw data are under-analysed. Heart rate variability (HRV) methods, in which beat-to-beat interval lengths are extracted and analysed, have been extensively studied. However, this approach discards the majority of the raw data. Objective: Our aim is to detect changes in the shape of the waveform in long streams of blood pressure data. Approach: Our approach involves extracting key features from large complex data sets by generating a reconstructed attractor in a three-dimensional phase space using delay coordinates from a window of the entire raw waveform data. The naturally occurring baseline variation is removed by projecting the attractor onto a plane from which new quantitative measures are obtained. The time window is moved through the data to give a collection of signals which relate to various aspects of the waveform shape. Main results: This approach enables visualisation and quantification of changes in the waveform shape and has been applied to blood pressure data collected from conscious unrestrained mice and to human blood pressure data. The interpretation of the attractor measures is aided by the analysis of simple artificial waveforms. Significance: We have developed and analysed a new method for analysing blood pressure data that uses all of the waveform data and hence can detect changes in the waveform shape that HRV methods cannot, which is confirmed with an example, and hence our method goes ‘beyond HRV’.

Measurement of cardiovascular state using attractor reconstruction analysis

Attractor reconstruction (AR) analysis has been used previously to quantify the variability in arterial blood pressure (ABP) signals. Since ABP signals are only available in a minority of clinical scenarios, we sought to determine whether AR could also be performed on more widely available pho-toplethysmogram (PPG) signals. AR analysis was performed on simultaneous ABP and PPG signals before, during and after a change in cardiovascular state. A novel quality metric was used to eliminate windows of low quality AR. A high level of agreement was found between the detected periodicity of each signal. The remaining cardiovascular parameters derived using AR analysis exhibited similar trends between the two signals in response to the change in state, although there was poor agreement between their absolute values. This demonstrates the feasibility of applying AR to the PPG signal, increasing the range of patients in whom cardiovascular state can be measured using AR analysis.