Two-Part Reactive Formulations for Intranasal Delivery of Benzodiazepines

University of Minnesota Ph.D. dissertation. August 2019. Major: Pharmaceutics. Advisor: Ronald Siegel. 1 computer file (PDF); xxi, 264 pages.A seizure emergency occurs when an individual experiences a seizure that lasts for more than five minutes (status epilepticus) or multiple distinct seizures with incomplete recovery between them (acute repetitive seizures). A patient experiencing a seizure emergency must be treated as quickly as possible to avoid lasting neurological damage and other life-threatening complications. Benzodiazepines are the primary rescue medications used to treat seizure emergencies, the most commonly used being intravenous lorazepam or rectal diazepam. Despite the effectiveness of these drugs, the delivery routes are not ideal for first-line, outpatient treatments. A skilled caregiver must be present to administer drugs intravenously, and the social stigma associated with rectal administration results in low compliance. Intranasal delivery is an attractive alternative because it requires little training, is easily performed by non-medical personnel, carries a low risk of injury to the patient, and can provide a rapid therapeutic effect. However, formulating a benzodiazepine nasal spray is challenging because these drugs have very low aqueous solubilities. One strategy to circumvent solubility issues relies on in situ production of drug from co-administration of soluble reactants. Herein, we describe how a prodrug/enzyme reaction or an acid/base reaction can be used to deliver a benzodiazepine in an aqueous vehicle with a volume and pH appropriate for intranasal administration. When the soluble components of these two-part reactive formulations are mixed at the time of administration, a metastable supersaturated solution of the benzodiazepine is produced. The supersaturated state of the benzodiazepine provides a large chemical activity gradient for rapid absorption across the nasal mucosa and into systemic circulation. In vitro characterization of the reaction kinetics and supersaturation behaviors for diazepam prodrug/enzyme reactions, midazolam prodrug/enzyme reactions, and midazolam acid/base reactions demonstrated that these two-part formulations generate predictable levels of supersaturated drug. An in vivo pharmacokinetic study in rats showed that rapid absorption and high bioavailability of diazepam results from intranasal administration of a diazepam prodrug/enzyme formulation. Furthermore, a dual chamber nasal spray device capable of mixing and atomizing the components of a two-part formulation was designed, prototyped, and tested. These two-part reactive formulations, coupled with the specialized nasal spray device, exemplify a new intranasal drug delivery strategy that may be applicable to a variety of other drugs with poor stability or low solubility

Maintaining Hope/ Encouraging Perspective in Special Education

Having a child with moderate to severe disabilities is a life-altering experience for many families. This study is an exploration of the relationship that exists between the parents of children with moderate to severe disabilities and special education professionals. It is an attempt to gain a deeper understanding of the parental perspective on the complexities of that relationship, and to investigate how that relationship is negotiated through stories told by eight parents about their experiences with the professionals in the schools their children attend. This study is also focused on how parents, school systems, and societal understandings of disability and difference intersect in the realm of providing educational opportunities and care for children with disabilities. This is a Narrative Inquiry study, and it is influenced by feminist methodological considerations. Interviews conducted with participants generated a collection of life-story case studies. Findings were analyzed for commonality and seven themes emerged from the data. They include the impact of having a child with a disability on the family, expectations, special education placement issues, communication, the quality of interactions between parents and professionals, systemic barriers to relationships, and the process of accepting or making peace with having a child with disabilities. The conceptual framework for analysis involves the ethics of care, power relationships in school and the phenomenon of ambiguous loss. Results suggest that conflict is inevitable because parents and professionals view children through different lenses, but that thoughtful and compassionate efforts on the part of educators can develop into relationships that provide welcome support and understanding to families during difficult periods of adjustment and transition

Combining wearables and nearables for patient state analysis

Recently, ambient patient monitoring using wearable and nearable sensors is becoming more prevalent, especially in the neurodegenerative (Rett syndrome) and sleep disorder (Obstructive sleep apnea) populations. While wearables capture localized physiological data such as pulse rate, wrist acceleration and brain signals, nearables record global passive data including body movements, ambient sound and environmental variables. Together, wearables and nearables provide a more comprehensive understanding of the patient state. The processing of data captured from wearables and nearables have multiple challenges including handling missing data, time synchronization between sensors and developing data fusion techniques for multimodal analysis. The research described in this thesis addresses these issues while working on data captured in the wild. First, we describe a Rett syndrome severity estimator using a wearable biosensor and uncover physio-motor biomarkers. Second, we present the applications of an edge computing and ambient data capture system for home and clinical environments. Finally, we describe a transfer learning and multimodal data fusion based sleep-wake detector for a mixed-disorder elderly population. We show that combining data from wearables and nearables improves the performance of sleep-wake detection in terms of the F1-score and the Cohen’s kappa compared to the unimodal models.Ph.D

Federal Register

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NOTIFICATION !!!

All the content of this special edition is retrieved from the conference proceedings published by the European Scientific Institute, ESI. http://eujournal.org/index.php/esj/pages/view/books The European Scientific Journal, ESJ, after approval from the publisher re publishes the papers in a Special edition

NOTIFICATION !!!

All the content of this special edition is retrieved from the conference proceedings published by the European Scientific Institute, ESI. http://eujournal.org/index.php/esj/pages/view/books The European Scientific Journal, ESJ, after approval from the publisher re publishes the papers in a Special edition

NOTIFICATION !!!

All the content of this special edition is retrieved from the conference proceedings published by the European Scientific Institute, ESI. http://eujournal.org/index.php/esj/pages/view/books The European Scientific Journal, ESJ, after approval from the publisher re publishes the papers in a Special edition

NOTIFICATION !!!

All the content of this special edition is retrieved from the conference proceedings published by the European Scientific Institute, ESI. http://eujournal.org/index.php/esj/pages/view/books The European Scientific Journal, ESJ, after approval from the publisher re publishes the papers in a Special edition