Nasal Administration: A Tool for Tomorrow's Systemic Administration of Drugs

By its anatomy and physiology, due to the great amount of air treated there, the nasal route represents a very interesting possibility for the administration of products degraded in the gastro-intestinal tract or inhibited by the first hepatic pass. The nasal dosage forms most studied are bioadhesive hydrogels and microspheres, especially for the systemic administration of peptides.     

Development of a Trans-Mucosal Controlled-Release Device for Systemic Delivery of Antianginal Drugs Pharmacokinetics and Pharmacodynamics

Oral mucosa is well-known to be one of the best routes for drug absorption. But very few R & D works have been initiated to investigate the feasibility of using this site to control drug delivery. A transmucosal controlled-release device, which is capable of achieving excellent absorption and controlled release of drugs, has been developed. The device is a tabletshaped mucoadhesive system which is composed of two layers. The upper layer is a fast-release layer and the lower layer is a sustained-release layer, and designed to be applied between buccal and gingival mucosae. Both layers are formulated from synthetic polymers to control the release of drugs.

Isosorbide dinitrate(ISDN), a well-documented antianginal drug, is known to be susceptible to extensive presystemic elimination when taken orally. It was used as the candidate drug and the systemic bioavailability was studied in human and observed to be improved by as much as 5 fold when compared to a marketed oral sustained-release tablet; On the other hand, much smaller amount of metabolites was formed. The plasma profile of ISDN has also been observed to be substantially prolonged (12 hrs as compared to less than 1 hr for sublingual tablet and spray product on the market). These observations have demonstrated that this device is capable of not only bypassing hepatic “first-pass” metabolism but also having a sustainedrelease property of prolonging the release of ISDN.

Clinical studies performed in the anginal patients for up to one year have demonstrated the therapeutic benefits of this device in achieving a substantial reduction in the frequency of anginal attacks.

This type of device was also applied to the systemic delivery of another antianginal drug, Nifedipine, by employing a formulation with longer sustained drug release property. Again, the clinical results demonstrated that a prolonged duration of therapeutic plasma concentration has also been accomplished.     

A K‐12/University Partnership: Creating Tomorrow's Engineers*

Supported by the National Science Foundation, the GK‐12 Fellows program at the University of Colorado at Boulder explores innovative ways for engineering graduate students to use engineering as the vehicle to provide K‐12 classroom instruction and hands‐on experiences that integrate physical sciences, mathematics, engineering and technology. Engineering “Fellows” fill a crucial gap in the two‐way exchange of content and pedagogy between the College of Engineering and Applied Science and the K‐12 community of learners. The active presence of real world, engineering role models in K‐12 classrooms improves the quality of math and science content, and introduces engineering to teachers and young students as a potential career path. Working through the University's graduate program legitimizes K‐12 outreach as a valid, and satisfying, academic endeavor for graduate students.     

Multidisciplinary Project: A Tool for Learning the Subject

In recent years, with the national trend toward business downsizing, job market needs have changed. Small companies are becoming the primary employers of engineers and technologists, who must assume multidisciplinary roles. Multidisciplinary projects can provide students with valuable preparation for this requirement. The objectives of the work described in this paper are: 1) help technology students develop, to some extent, the abilities of engineering students, 2) to enhance technology students' interest in a multidisciplinary curriculum. To help achieve these objectives, students at Temple University were given an electromechanical project to design a model of a smart conveyor belt system that could recognize the size of different blocks. Statistical analysis of a confidential student survey showed that a significant number of students positively rated the benefits of working on the project. Survey performance indices included pedagogy, interactions with Electrical Engineering students and faculty, and obtaining hands-on experience. Project students scored statistically higher on a theory test, and 34% of the students were motivated to complete a minor in electromechanical engineering technology because of the interdisciplinary project.     

The Effect of Chitosan Molecular Weight on the Characteristics of Spray-Dried Methotrexate-Loaded Chitosan Microspheres for Nasal Administration

In this article, the effect of the chitosan molecular weight (MW) on the characteristics of methotrexate (MTX)-encapsulated non-cross-linked chitosan microspheres was studied. Microspheres composed of low-molecular-weight (LMW, 40,000 Da), medium-molecular-weight (MMW, 480,000 Da) and high-molecular-weight (HMW, 850,000 Da) chitosan with the same degree of deacetylation (96%) were obtained by a simple spray-drying method. The MW of chitosan had a noticeable influence on the size distribution, encapsulation efficiency, micromeritic properties (angle of repose and bulk density), controlled release behavior, and mucoadhesive properties. The entrapment efficiencies were in the range of 90–99%. Spray-dried microspheres had a D₅₀ value of 3.3–4.9 μm, which was suitable for nasal insufflations. The microspheres with LMW chitosan have the best flowability and highest bulk density but were found to be poor in terms of adhesion and in controlling the release behavior of MTX. The MMW chitosan microspheres exhibited the strongest adhesion to the mucosal surface, and the angle of repose values were between 34 and 47 degrees. They could control the release rate by modifying the drug/polymer ratios. Microspheres with HMW chitosan exhibited a lower adhesion than MMW chitosan and a lower release rate of MTX. The physical state of MTX in the chitosan matrix was studied by differential scanning calorimetry, which indicated the presence of a solid dispersion of the amorphous drug in the chitosan matrix. Nasal ciliotoxity showed only minor cilia irritation due to the microspheres, and consequently, they are suitable for nasal drug delivery.     

Course Assessment Plan: A Tool for Integrated Curriculum Management

As we enter the 21^st Century in engineering education, a common desire exists to improve curriculum structure, integration and assessment. Much has been written and discussed concerning the process for assessing and/or revising a program curriculum. Studies are beginning to show the positive effects of well‐integrated curricula where assessment methods are applied consistently. There has also been much written to support individual course assessment and revision. What is missing in many instances is a credible link between program‐level curriculum management and course assessment. At the United States Military Academy (USMA) at West Point, an integrating tool within the academy's assessment model, called a Course Assessment Plan, has been developed and refined. The course assessment process and the resulting written documentation provide an essential link between a program curriculum and its constituent courses. The plan's process, content, and an example outcome are the major focus of this paper.     

A Software Tool for Reliability Estimation

Over the years, several tools have been developed to estimate the reliability of hardware and software components. Typically, such tools are either for hardware or software. This paper presents the Software Tool for Reliability Estimation (STORE), which can be used for systems containing hardware and/or software components. For software components, exponential, Weibull, gamma, power, geometric, and inverse-linear models were implemented. Goodness of fit statistics are provided for each model. The user can select the most appropriate model for a given system configuration and failure data. The STORE program can analyze series, parallel, and complex systems. Tieset and cutset algorithm is utilized to determine the reliability of a complex system. The paper presents several examples to demonstrate the software tool.     

A Tool for Interrogation of Macromolecular Structure

Our program BABELPDB allows browsing and interrogating the native and derived structural features of biomacromolecules using data obtained from the Protein Data Bank （PDB）. Major features of BABELPDB are： （1） convert from PDB to other formats, （2） add or remove H-atoms, （3） strip the crystallization water molecules and （4） separate the ct-carbons （Cα）. The co-ordinates obtained with BABELPDB permit characterizing the presence of H-bonds. The algorithm for detecting H-bonds is implemented in our program TOPO for the theoretical simulation of the molecular shape, An example is given to illustrate the capabilities of the software： the calculation of the fractal dimension of the lysozyme molecule with （1.908） and without （1.920） H-atoms. The figures compare well with reference calculations performed with our version of program GEPOL and results from Pfeifer et al. For proteins, Cα-skeleton extracted with BABELPDB allows drawing the ribbon image, which determines their secondary structure.     

A Simplified Rat Model for Studying Nasal Drug Absorption

Abstract

A simple and rapid rat model for studying nasal drug absorption was developed. In this model, a solution of the test drug, propranolol hydrochloride, was gradually deposited into the nasal cavity of an anesthetized rat through a PE-20 polyethylene catheter connected to a tuberculin syringe via a 30 gauge needle. The extent of drug bioavailability was assessed by measuring propranolol blood levels and the changes in heart rate. For comparative purposes, identical experiments were repeated using the intravenous route of administration, an established rat model requiring surgery, and the proposed model after tracheal cannulation and esophageal li-gation. Although the pharmacokinetic parameters for the various models tested indicated bioavailabilities that were quite similar to that obtained by the intravenous route of administration, the drop in heart rates appeared to be more pronounced with the proposed model than with any of the other two models. In addition to its simplicity, the proposed rat model represents a less stressful and more physiological means of delivering a drug by the nasal route.     

A Simplified Rat Model for Studying Nasal Drug Absorption

A simple and rapid rat model for studying nasal drug absorption was developed. In this model, a solution of the test drug, propranolol hydrochloride, was gradually deposited into the nasal cavity of an anesthetized rat through a PE-20 polyethylene catheter connected to a tuberculin syringe via a 30 gauge needle. The extent of drug bioavailability was assessed by measuring propranolol blood levels and the changes in heart rate. For comparative purposes, identical experiments were repeated using the intravenous route of administration, an established rat model requiring surgery, and the proposed model after tracheal cannulation and esophageal li-gation. Although the pharmacokinetic parameters for the various models tested indicated bioavailabilities that were quite similar to that obtained by the intravenous route of administration, the drop in heart rates appeared to be more pronounced with the proposed model than with any of the other two models. In addition to its simplicity, the proposed rat model represents a less stressful and more physiological means of delivering a drug by the nasal route.     

A Flexible Simulation Tool for Manufacturing-cell Design

We present a general manufacturing-cell simulation model for evaluating the effects of world-class manufacturing practices on expected cell performance. The modular structure of the simulation provides the flexibility to analyze a wide variety of manufacturing cells. We formulate a comprehensive annualized cost function for evaluation and comparison of alternative cell configurations. A case study involving assembly of printed circuit boards illustrates the potential benefits of using this tool for cell design and analysis. The simulation model is intended for use in a two-phase approach to cell design that is based on simulated experimentation and response surface analysis as detailed in a companion paper.     

A Flexible Simulation Tool for Manufacturing-cell Design

We present a two-phase approach to design and analysis of manufacturing cells based on simulated experimentation and response surface methodology using a general manufacturing-cell simulation model. The first phase involves factor-screening simulation experiments to identify design and operational factors that have a significant effect on cell performance as measured by a comprehensive annual cost function. In the second phase of experimentation, we construct simulation (response surface) meta-models to describe the relationship between the significant cell design and operational factors (the controllable input parameters) and the resulting simulation-based estimate of expected annual cell cost (the output response). We use canonical and ridge analyses of the estimated response surface to estimate the levels of the quantitative input factors that minimize the cell's expected annual cost. We apply this methodology to an assembly cell for printed circuit boards. Compared to the current cell operating policy, the simulation metamodel-based estimate of the optimum operating policy is predicted to yield average annual savings of approximately $425 000, which is a 20% reduction in annual cost. In a companion paper, we detail the structure and operation of the manufacturing-cell simulation model.     

Anionic Mucoadhesive Polymers as Auxiliary Agents for the Peroral Administration of (Poly)Peptide Drugs: Influence of the Gastric Juice

The incorporation of (poly)peptide drugs in mucoadhesive polymers is a promising strategy for their peroral administration. In this study, the protective effect of various polymers toward an artificial gastric fluid and the influence of an enteric coating on the adhesive properties have been investigated. Tablets containing 30 mg of carbomer (C934P), neutralized carbomer (NaC934P), or sodium carboxymethylcellulose (NaCMC), 0.1 mg of the model protein peroxidase, and 19.9 mg of mannitol were incubated at 37°C for 2.5 hr with a simulated gastric fluid with and without pepsin. All polymers—although anionogenic—displayed quick swelling behavior in the acid milieu, leading to an unintended protein release. Moreover, pepsin is capable of penetrating into the polymeric carrier systems, thereby rapidly degrading the embedded protein. Enteric coating, on the other hand, leads to strongly reduced adhesive properties. Only NaC934P tablets coated with polymethacrylate containing 9% triethylcitrate displayed no significant (p <. 05) reduction in adhesive strength. Results give essential basic information for the development of peroral (poly)peptide dosage forms based on mucoadhesive polymers.     

Residual Magnetic Flux Leakage: A Possible Tool for Studying Pipeline Defects

Simulated defects of different shapes and sizes were created in a section of API X70 steel line pipe and were investigated using a residual magnetic flux leakage (MFL) technique. The MFL patterns reflected the actual shape and size of the defects, although there was a slight shift in their position. The defect features were apparent even at high stresses of 220 MPa when the samples were magnetized at those particular stresses. However, unlike the active flux technique, the residual MFL needs a sensitive flux detector to detect the comparatively weaker flux signals.     

Initiated Chemical Vapor Deposition: A Versatile Tool for Various Device Applications

Advances in device technology have been accompanied by the development of new types of materials and device fabrication methods. Considering device design, initiated chemical vapor deposition (iCVD) inspires innovation as a platform technology that extends the application range of a material or device. iCVD serves as a versatile tool for surface modification using functional thin film. The building of polymeric thin films from vapor phase monomers is highly desirable for the surface modification of thermally sensitive substrates. The precise control of thin film thicknesses can be achieved using iCVD, creating a conformal coating on nano‐, and micro‐structured substrates such as membranes and microfluidics. iCVD allows for the deposition of polymer thin films of high chemical functionality, and thus, substrate surfaces can be functionalized directly from the iCVD polymer film or can selectively gain functionality through chemical reactions between functional groups on the substrate and other reactive molecules. These beneficial aspects of iCVD can spur breakthroughs in device fabrication based on the deposition of robust and functional polymer thin films. This review describes significant implications of and recent progress made in iCVD‐based technologies in three fields: electronic devices, surface engineering, and biomedical applications.