Conventional solid dosage forms often lead to fluctuations which exceed the maximum safe therapeutic level and/or decline below the minimum effective level. It is recognised that many drugs for chronic administration should be administered on a schedule that maintains plasma drug concentration within the therapeutic window. Research in controlled release dosage forms aims at designing a system with a zero-order input (eg, ideally to deliver 8.33% of the dose per hour over a 12 hour duration), producing steady state plasma drug levels. Oral dministration of drugs prepared as a controlled release formulation is extremely popular, and has attracted the attention of pharmaceutical scientists during the last decade. This has been due to the simultaneous convergence of various factors (eg, discovery of novel polymers and devices, better understanding of formulation and physiological constraints, expiration of existing patents, prohibitive cost of developing new drug entities), involved in the development of these delivery systems. Controlled release oral products can be formulated as single or multiple unit dosage forms and the relative merits of multiple unit forms with their own rate controlling systems are well established. This work describes the development of a relatively inexpensive multiple-unit capsule dosage form of theophylline containing coated mini-tablets for drug delivery throughout the gastrointestinal tract. Preformulation studies on theophylline anhydrous included solubility and dissolution rate determinations. Techniques including X-ray powder diffraction, differential scanning colorimetry and infrared spectroscopy provided no evidence of true polymorphism after recrystallisation from various solvents. However, scanning electron micrographs showed the effects of solvent polarity and cooling rate on the size and shape of recrystallised particles. Theophylline granules were manufactured by using various binders and were film coated by fluidised bed technology with various proportions of ethylcellulose, containing varying amounts of PEG 1540. In vitro release rates were dependent upon coating thickness and the proportion of PEG, which, being water soluble, created pores in the coating during dissolution studies as observed by a scanning electron microscope. However, substantial proportions of the drug remained unreleased from the granules. In order to overcome the problems of drug retention, plain granules were used and theophylline mini-tablets (3 mm diameter, weighing 15 - 20 mg) were manufactured and film coated with various Eudragits ® and other polymeric mixtures (soluble and insoluble). In vitro dissolution profiles from samples enclosed in hard gelatin capsules were determined using the USPXXI paddle apparatus in test media at pH 1.2 (HCI), pH 5.4 and 7.4 (phosphate buffers) at 37'C. Monitoring of in vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in < 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasise the usefulness of an animal model for assessment of in vivo drug release and subsequent absorption during the development of modified release dosage forms. Mini-tablets were subjected to isothermal and cyclic stresses to reach conditions for up to 6 months at different temperatures and relative humidity. The film integrity was maintained but ageing of the coating occurred which impeded dissolution. Reduced drug release was temperature related while the effect of relative humidi% was insignific~t. Encapsulated mini-tablets (uncoated and coated with Eudragit RL and RS 2% w/w) equivalent to a 300 mg dose, were evaluated both in vitro and in vivo using beagle dogs. The pharmacokinetic parameters from single and multiple dose studies showed several advantages over Theo-Dur® 300 mg tablets. Precise dosage titration is possible by careful adjustment of the number of encapsulated mini-tablets. This multiple unit mini-tablet delivery system will allow for greater flexibility in dosage adjustment compared to the currently available preparations, allowing individualised fine dose titration in those patients requiring therapeutic drug monitoring. The developmentof the multiple unit mini-tablet formulation appears to provide an optimal dosage form with maximum flexibility in respect of dose, duration range and ease of production.

Elderly people, or those over 65 years of age, are known to comprise 10% of the United States population today and are projected to reach nearly 12% by the year 2000. Further, 5% of this population is reported to be institutionalized resulting in approximately 1.1 million chronic care patients or 0.5% of the population. The use of drugs in this population comprises approximately 25% of the prescription drug market in the United States which is directly related to the greater occurrence of pathological problems associated with the aging process. While it is evident that the beneficial outcome of drug therapies is partially related to the increased longevity observed in these elderly people, this population is also well-known to be the most prone to adverse drug reactions. Factors complicating drug use in the elderly include high usage, chronic therapy, long-term hospitalization, inappropriate and multiple prescribing of drugs, inadequate monitoring of adverse drug effects, susceptibility to physical deterioration and senility. Therefore, the objective of this project is to test the hypothesis that the quality and cost of drug therapy in SNF patients can be significantly improved by implementing measures to improve the utilization of drugs.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING / Bibliography: leaves 90-91. / by Brij Mohan Masand. / M.S.

Biopharmaceuticals, including proteins, DNA and vaccines, are one of the fastest growing segments of the overall pharmaceutical market. While the hypodermic injection, the most common delivery method for these molecules, is effective, it also has limitations, including low patient compliance, need for medically trained personnel and biohazardous sharps after delivery. The overall goal of this thesis was to develop a new delivery system for biopharmaceuticals, based on dissolving polymer microneedles, which is effective and more patient compliant than the hypodermic needle. Microneedles are microscopic needles that are large enough to insert into the skin to deliver drugs effectively, while being short enough to avoid the pain causing nerves deep in the skin. An additional benefit of polymer microneedles is that the needles completely dissolve in the skin, leaving behind no biohazardous sharps. There are significant material and fabrication issues that must be overcome in the development of this new device. The first part of this thesis focused on the development of a new fabrication process, based on in situ photopolymerization, for the creation of polymer microneedles. These microneedles were shown to successfully insert into the skin, dissolving within a minute to deliver the encapsulated cargo, and retain full activity of encapsulated proteins. Next, we applied the microneedle technology to the delivery of the influenza virus. We found that the reformulation process required to encapsulate the influenza virus in polymer microneedles did not affect the antigenicity or immunogenicity of the virus. In addition, we used coated metal microneedles to successfully immunize mice with the influenza virus, verifying the delivery capabilities of a microneedle system. Finally, we used the dissolving polymer microneedles to successfully immunize mice with the influenza virus, resulting in full protection against lethal challenge after one immunization. This immune response was equivalent to the control intramuscular injection. In conclusion, we have developed dissolving polymer microneedles as an effective and patient compliant delivery system for biopharmaceuticals. This system could be especially applicable to mass immunization efforts or home use, since it can be self-administered and allows for easy disposal with no biohazardous sharps.

Microneedles have been developed as a minimally invasive alternative to painful hypodermic needles to deliver modern biotherapeutics. Previously, several in-vitro and in-vivo animal studies have been conducted to show that microneedles increase skin permeability to a wide range of molecules that cannot cross the skin using conventional transdermal patches due to the skin's stratum corneum barrier. However, only a limited number of studies have been performed to study microneedle-based drug delivery in human subjects. Therefore, the objective of this study was to perform the first-in-humans microneedle studies to: a) characterize skin repair responses to solid microneedle insertion to determine the extent of increased skin permeability coupled with predictions of pharmacokinetics of drug delivered through premeabilized skin, b) determine the effect of hollow microneedle-based infusion parameters on flow conductivity of skin and pain and thereby identify barriers to fluid flow into the skin from hollow microneedles, c) assess the safety and efficacy of systemic therapeutic effects through measurement of pharmacokinetic parameters, pain and irritation for microneedle-based insulin delivery in type 1 diabetes subjects, and d) assess the safety and efficacy of local therapeutic effects though delivery of lidocaine to the skin. Results showed for the first time that solid microneedle-treated skin reseals rapidly (< 2 h) in the absence of occlusion whereas occluded skin reseals slowly (3-40 h) depending on microneedle geometry as determined by skin impedance measurements. Increased microneedle length, number, and cross-sectional area led to slower recovery kinetics in the presence of occlusion. This thesis also demonstrated that the flow conductivity of skin decreased as fluid was infused to the dermis through hollow microneedles due to the dense structure of the dermis. Microneedle retraction, low flow rates, and the addition of hyaluronidase helped increase flow conductivity. Microneedles were able to deliver 800 µl of saline to the dermis without causing significant pain. Further, microneedle-based insulin delivery in type 1 diabetes subjects revealed that microneedles provided faster pharmacokinetics and improved glycaemic control than conventional subcutaneous catheters. Lastly, microneedle-based lidocaine injection demonstrated that microneedles were less painful, as effective, and more preferred than hypodermic needles in anesthetizing clinically relevant areas.

The purpose of this study was to determine if there is a relationship between having military discipline, the military rank, the branch of service, the number of years served, reserve status and if these factors would affect a veterans' compliancy in taking daily medication.

Thesis submitted in fulfilment of the requirements for the degree Master of Technology: Nursing In the Faculty of Health and Wellness Sciences At the Cape Peninsula University of Technology, 2013 / The syringe driver is a battery-operated device which accurately delivers a continuous subcutaneous infusion of a combination of medication to alleviate symptoms, such as pain, nausea and vomiting, noisy moist breathing and preterminal restlessness. The researcher who works in a palliative care unit in Cape Town noticed the ambivalence and negative attitudes from family members regarding the use of the syringe driver. This gave rise to distress, conflict and ambivalence in patients and between family members. This study aimed to gain insight into the understanding, perceptions and expectations of families of terminally ill patients commenced on a syringe driver in a palliative care unit. A descriptive, qualitative research method was employed using semi-structured interviews, diaries, observation and documentation as the data collection methods. Data was coded and arranged into themes. Thematic analysis and coding were used to analyse the data during this study. This study found that the lack of education and written information were the two major contributing factors towards negative attitudes causing ambivalence in family members whose relatives were on a syringe driver. This study also highlighted the need for quality improvement control when using the syringe driver in the palliative care unit. The need for continuous education and written information and support for the immediate and extendedfamily members was evident. KEY WORDS: Syringe driver, Symptom control, Family members, Terminally ill, Palliative care unit.

De nos jours, la voie inhalée constitue le mode d’administration optimal dans le traitement de nombreuses affections respiratoires, et suscite beaucoup d’intérêt pour la délivrance systémique de médicaments. Cependant, le poumon est un organe complexe doté de mécanismes de défense efficients qui limitent la déposition des particules inhalées et les éliminent très rapidement. Cette voie d’administration fait donc l’objet de programmes de recherche intensifs visant à améliorer l’efficacité de la délivrance et la compliance du patient. Il faut néanmoins signaler que le nombre d’excipients dont l’innocuité a été démontrée en inhalation (sous forme de poudre sèche) reste extrêmement limité à l’heure actuelle. A cet égard, l’utilisation de microparticules lipidiques solides (mPLS), constituées d’un mélange de cholestérol et de phospholipides biodégradables et caractérisés par une température de transition de phase élevée, a été envisagée. Le procédé retenu pour la préparation de ces mPLS est la technique d’atomisation à température modérée (spray-drying).<p><p>\ / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Indiana University-Purdue University Indianapolis (IUPUI) / People with severe mental illness (SMI) often suffer from comorbid physical conditions that result in chronic morbidity and early mortality. Physical health decision-making is one area that has been largely unexplored with the SMI population. This study aimed to identify what factors contribute to the physical healthcare decision-making autonomy preferences of persons with SMI, and to identify the impact of these autonomy preferences on medication adherence. Ninety-five adults with SMI were recruited from an integrated care clinic located in a community mental health center. Fifty-six completed a three-month follow-up. Multiple linear regression for hypothesis 1 (n=95) and hierarchical regression for hypothesis 2 (n=56) were used to analyze data on personal characteristics, physical health decision-making autonomy preferences and medication adherence. For the open-ended questions, thematic analysis was used to uncover facilitators and barriers to medication adherence. With this sample, being male predicted greater desired autonomy, and having less social support predicted less desired autonomy. When background characteristics were held constant, autonomy preferences and perceived autonomy support from the physician only contributed an additional 1% of the variance in medication adherence. Lastly, participants reported behavioral factors and having family/personal support to take medications as facilitators to medication adherence for physical health care, while citing financial and other resource limitations as barriers.

Indiana University-Purdue University Indianapolis (IUPUI) / Medication administration error remains a leading cause of preventable death. A gap exists in understanding attentional dynamics, such as nurse situation awareness (SA) while managing interruptions during medication administration. The aim was to describe SA during medication administration and interruption handling strategies. A crosssectional, descriptive design was used. Cognitive task analysis (CTA) methods informed analysis of 230 interruptions. Themes were analyzed by SA level. The nature of the stimuli noticed emerged as a Level 1 theme, in contrast to themes of uncertainty, relevance, and expectations (Level 2 themes). Projected or anticipated interventions (Level 3 themes) reflected workload balance between team and patient foregrounds. The prevalence of cognitive time-sharing during the medication administration process was significant or may be remarkable. Findings substantiated the importance of the concept of SA within nursing as well as the contribution of CTA in understanding the cognitive work of nursing during medication administration.