Estimating hand-grip forces causing Cumulative Trauma Disorder

Wearable sensors have garnered considerable interest because of their potential for various applications. However, much less has been studied about the Stretchsense pressure sensor characteristics and its workability for industrial application to prevent potential risk situations such as accidents and injuries. The proposed study helps investigate Stretchsense pressure sensors\u27 applicability for measuring hand-handle interface forces under static and dynamic conditions. The BendLabs sensors - a multi-axis, soft, flexible sensing system was attached to the wrist to evaluate the wrist angle deviations. In addition, the StretchSense stretch sensors were attached to the elbow joint to help estimate the elbow flexion/extension. The research tests and evaluates the real-time pressure distribution across the hand while performing given tasks and investigates the relationship between the wrist and elbow position and grip strength. The research provides objective means to assess the magnitudes of high pressures that may cause pressure-induced discomfort and pain, thereby increasing the hand\u27s stress. The experiment\u27s most significant benefit lies in its applicability to the actual tool handles outside the laboratory settings

EXTRACTION OF A WATER SOLUBLE BIOACTIVE HYPOXOSIDE AND ITS DEVELOPMENT INTO AN ETHOSOMAL SYSTEM FOR DEEP DERMAL DELIVERY

Objective: This study was aimed to extract Hypoxoside, a water soluble phytochemical, from the corms of Hypoxis hemerocallidea, and incorporate it into a suitable transdermal carrier system to increase its penetrability and deep dermal delivery for potential antioxidant and anticancer activity.Methods: The extraction of Hypoxis hemerocallidea corms was carried out by continuous hot extraction method. This extract (20 mg/ml) was loaded into ethosomal vesicular system by cold method and optimized by varying proportions of lecithin and ethanol. The optimized system was then subjected to characterization in terms of particle size, polydispersity index (PDI), entrapment efficiency and invitro permeation and penetration studies.Results: The optimized vesicle with size of 176.2±11 nm, PDI of 0.231 and entrapment efficiency of 74.2±2.3% was obtained which showed a sustained release pattern of the hypoxoside from the vesicular system. Confocal laser scanning microscopy (CLSM) demonstrated that the vesicles were able to efficiently traverse the skin to a depth of 117.29 µm whereas the mechanism of vesicle-skin interaction was confirmed by histopathological study.Conclusion: The study indicated that with the development of an efficient delivery system a water soluble phytochemical with antioxidant and anticancer properties can be efficiently delivered to the skin.Â

Design of energy efficient high speed I/O interfaces

Energy efficiency has become a key performance metric for wireline high speed I/O interfaces. Consequently, design of low power I/O interfaces has garnered large interest that has mostly been focused on active power reduction techniques at peak data rate. In practice, most systems exhibit a wide range of data transfer patterns. As a result, low energy per bit operation at peak data rate does not necessarily translate to overall low energy operation. Therefore, I/O interfaces that can scale their power consumption with data rate requirement are desirable. Rapid on-off I/O interfaces have a potential to scale power with data rate requirements without severely affecting either latency or the throughput of the I/O interface. In this work, we explore circuit techniques for designing rapid on-off high speed wireline I/O interfaces and digital fractional-N PLLs. A burst-mode transmitter suitable for rapid on-off I/O interfaces is presented that achieves 6 ns turn-on time by utilizing a fast frequency settling ring oscillator in digital multiplying delay-locked loop and a rapid on-off biasing scheme for current mode output driver. Fabricated in 90 nm CMOS process, the prototype achieves 2.29 mW/Gb/s energy efficiency at peak data rate of 8 Gb/s. A 125X (8 Gb/s to 64 Mb/s) change in effective data rate results in 67X (18.29 mW to 0.27 mW) change in transmitter power consumption corresponding to only 2X (2.29 mW/Gb/s to 4.24 mW/Gb/s) degradation in energy efficiency for 32-byte long data bursts. We also present an analytical bit error rate (BER) computation technique for this transmitter under rapid on-off operation, which uses MDLL settling measurement data in conjunction with always-on transmitter measurements. This technique indicates that the BER bathtub width for 10^(−12) BER is 0.65 UI and 0.72 UI during rapid on-off operation and always-on operation, respectively. Next, a pulse response estimation-based technique is proposed enabling burst-mode operation for baud-rate sampling receivers that operate over high loss channels. Such receivers typically employ discrete time equalization to combat inter-symbol interference. Implementation details are provided for a receiver chip, fabricated in 65nm CMOS technology, that demonstrates efficacy of the proposed technique. A low complexity pulse response estimation technique is also presented for low power receivers that do not employ discrete time equalizers. We also present techniques for implementation of highly digital fractional-N PLL employing a phase interpolator based fractional divider to improve the quantization noise shaping properties of a 1-bit ∆Σ frequency-to-digital converter. Fabricated in 65nm CMOS process, the prototype calibration-free fractional-N Type-II PLL employs the proposed frequency-to-digital converter in place of a high resolution time-to-digital converter and achieves 848 fs rms integrated jitter (1 kHz-30 MHz) and -101 dBc/Hz in-band phase noise while generating 5.054 GHz output from 31.25 MHz input

P-glycoprotein-dependent pharmacokinetics of irinotecan and its active metabolite, SN-38 in rats: Effect of verapamil

We have recently demonstrated that the oral bioavailability of irinotecan (80 mg/kg) can be increased at least 7-fold by co-administration of the P-gp blocker verapamil (25 mg/kg, Oral). As a result, co-treatment with P-gp inhibitor could be a useful strategy for bioavailability enhancement. However, in view of narrow therapeutic index, the co-administration of irinotecan and verapamil may result in unanticipated toxicities. Therefore, dose optimisation studies of irinotecan were performed when it is given in conjunction with a P-gp inhibitor. For dose optimization study, the bioavailability and pharmacokinetic parameters were studied in rats after oral administration of irinotecan at three doses (i.e. 20, 40 and 80 mg/kg) alone and in combination with verapamil (25 mg/kg, oral). The area under the plasma-concentration time curve (AUC) of irinotecan at 20, 40 and 80 mg/kg was 3.51 ± 1.20, 8.81 ± 1.93 and 14.03 ± 2.18 h µg/ml, respectively which after treatment with verapamil, increased dose dependently to 7.84 ± 1.20, 19.94 ± 2.39 and 61.71 ± 15.0 h µg/ml, respectively. In addition to irinotecan, plasma concentrations of SN-38, one of the major active metabolite of irinotecan, were also monitored. The less than proportional increase in SN-38 AUC from 20 to 80 mg/kg is consistent with the saturation of carboxylesterase. Our results indicate that oral drug treatment of irinotecan in presence of temporary P-gp inhibition could be as equally safe and effective as intravenous administration. Nevertheless, safe P-gp inhibitors need to be identified as alternatives to verapamil for development of efficacious oral irinotecan formulations

Uncovering caregiver concerns: 5 key issues that still remain unresolved in administration of oral medicines for children in India

INTRODUCTION: Administration devices play a very crucial role in achieving a drug’s therapeutic effect. Children are often dosed with oral liquids, but dosing devices don’t have the accuracy needed, putting them at risk of inaccurate and suboptimal dosing. The availability and use of administration devices may vary throughout the world. Multiple surveys in UK, Europe and Japan have shown diverging practices by parents/caregivers. The aim of the present investigation was to conduct a larger Pan-India study through a series of workshops to understand the use and challenges of traditional devices and assess the need of innovative administration devices for liquid orals in India. METHODS: Administration devices play a very crucial role in achieving a drug’s therapeutic effect. Children are often dosed with oral liquids, but dosing devices don’t have the accuracy needed, putting them at risk of inaccurate and suboptimal dosing. The availability and use of administration devices may vary throughout the world. Multiple surveys in UK, Europe and Japan have shown diverging practices by parents/caregivers. The aim of the present investigation was to conduct a larger Pan-India study through a series of workshops to understand the use and challenges of traditional devices and assess the need of innovative administration devices for liquid orals in India. RESULTS: Across the four regions (4 metro cities) involved in the study, 271 caregivers agreed to participate in the workshops. 17.7 % administered solid dosage forms, 81.2 % administered liquid dosage form and the remaining 1.1 % opted for others. TRADITIONAL DEVICES: Caregivers reported the use of measuring cups (41.4 %) followed by household spoons (25.8 %), droppers (15.3 %), measuring spoons (2.6 %), and other dosing devices (5.5 %) for measuring oral liquids. 8.0 % did not use any of the dosing devices as they were administrating tablets and/or capsules. The ease-of-use score was the highest for the dropper (2.67 ± 0.68) and the lowest for the measuring spoon (2.00 ± 1.00). The reported challenges were categorised into five categories which also influences the preference of using administration devices. This includes device design, user experience and usability, sociocultural factors, such as beliefs, knowledge and education, regulatory, and market/distribution. INNOVATIVE DEVICES: The majority of the caregivers (86.7 %) were not aware of any of the innovative devices shown to them. 58.7 % were willing to use it if was recommended by the doctor, 1.5 % of caregivers would use it on pharmacists’ recommendation and 37.6 % parents would use it if came along with the medicine. The criteria considered by the parents for use of the innovative devices in the descending order were Doctor’s recommendation > Quality > Cost > Packed in medicine > Ease of use > Availability/accessibility. There were no differences observed among the low and high socioeconomic status of caregviers regarding the use of traditional devices, challenges faced and awareness about innovative devices. Overall, the study revealed heterogeneity in the SES for the use of administration devices in the four zones. The association of SES and opinion on the use of administration devices was demonstrated with no statistically significant interaction between caregiver SES and the use of administration devices. CONCLUSION: The workshop revealed the prevalence of traditional dosing devices like measuring cups, household spoons among the caregivers. It highlighted key issues with the use of appropriate administration devices for correct and accurate dosing in children that remain unresolved and prevalent in India. This study reflects on the needs of the target community; thus hope will help facilitate the development of locally sustainable solutions to improve the administration of medicines in children in India

In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA), ácido fúlvico (FA), β-ciclodextrina (β-CD), 2-hidroxipropil-β-ciclodextrina (HP-β-CD) e cafeína (Caff). O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional, calorimetria de varredura diferencial (DSC), difração de raios-X (XRD), ressonância magnética nuclear (RMN) e espectroscopia de massas. Além disso, os complexos foram avaliados in vivo, em ratas, no tocante à sua eficácia no tratamento de candidíase vaginal. Entre os cinco complexos testados, o complexo de ácido fúlvico-itraconazol foi o que apresentou melhor solubilidade, bem como melhor eficácia in vivo e, portanto, pode ser explorado para o desenvolvimento de uma formulação comercial para o tratamento de candidíase vaginal

Stepping into small shoes: Gaining user perspective on appropriate administration devices for paediatric medication in India

A cross sectional pan-India study about use of administration devices for paediatric oral and inhalation medicines was conducted with a diverse pool of participants of various age groups. Via 634 respondents from more than 15 states in India, this study has identified the administration devices commonly used by parents/caregivers for children 0 to 18 years and by children over 10 years. It has provided insights on device ease of use, challenges faced and recommendations to facilitate the correct use of administration devices for paediatric oral and inhalation medicines. Ethics approval (DPSRU-BREC/2020/A/008)) was obtained from the Biomedical Research Ethics Committee of Delhi Pharmaceutical Sciences and Research University. The survey was completed by parents only (n = 514) and jointly by both parents and children (n = 120). The mean age of the child was 7.2 ± 4.96 years. 72% of the respondents reported that an oral medicine had been taken recently, 6.3% reported that an inhaled medicine had been taken and the remaining 21.9% reported that both an oral and inhaled medicine had been taken. The use of measuring cup was most prevalent followed by household spoons. The mean of the score for ease of use was found to be highest 4.6 ± 0.50 for oral syringe and lowest (3.8 ± 0.76) for measuring cups. The majority of them found the oral device easy to use. Difficulties were reported mostly for measuring cups and household spoons and were related to a lack of user instructions and measuring difficulties. The respondents who found the device easy to use had mostly received clear instructions from healthcare professionals. Compared to oral devices, there were very limited responses for inhalation devices (n = 175/634). Nebulisers with facemasks were most frequently used followed by manually actuated Metered dose inhalers with and without spacer. The mean of the ease-of-use score for dry powder inhalers was found to be highest (4.2 ± 0.37) followed by mist inhalers (4.0 ± 0) and manually actuated pressurised metered dose inhalers (4.0 ± 0.71). The nebulisers with facemask were reported to be difficult to use by most of the respondents despite receiving clear instructions from healthcare professionals.// The study findings add evidence to the understudied area of user experiences and perspectives on administration devices for oral and inhalation medicines in India. It highlights a need for initiatives to improve the usability, availability, and affordability of administration devices for children in India. Awareness on the importance of proper use of devices needs to be raised and sustained about the existence of affordable administration devices

A novel and multifunctional excipient for vaginal drug delivery

The present study explores the pharmaceutical potential of a natural organic matter (fulvic acid) for sustained release, acid buffering capacity and mucoadhesion in vaginal drug delivery. The antifungal drug, Itraconazole, was first converted into inclusion complexes with fulvic acid (1:1 & 1:2 molar ratio) and then characterized by Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT IR) and Mass Spectroscopy. Results were also authenticated by conformational analysis. Solubility analysis of complexes yielded different thermodynamic parameters and explained the driving force for solubilisation when the pH was varied in an acidic range. MTT assays were also performed to assess the potential in vitro cell toxicity of the complexes in comparison to the neat drug. The complexes were then formulated into tablets and optimized for hardness, mucoadhesion and release profiles. The optimized tablets presented with satisfactory mucoadhesion, acid buffering and spreading ability. Moreover, the antifungal activity of the formulation was also increased due to improved aqueous solubility of the drug despite the larger size of the complex. The study also indicated the potential use of fulvic acid as a functional excipient in the preparation of a vaginal drug delivery system (VDDS)