Diabetes has been labelled as one of the largest crises in the twenty-first century. Saudi Arabia is one of the top 10 countries for prevalence of diabetes and one in five people has the condition. Medication adherence assessment is vital to help clinicians reach therapy outcomes and identify gaps in patient management. The aim of this PhD was to explore oral hypoglycaemic medication (OHM) adherence in patients with Type 2 diabetes patients in Saudi Arabia and to identify factors associated with OHM adherence. The aim was addressed by: 1) Conducting a systematic review to identify which tools could be used to measure adherence to OHM as well as to quantify adherence levels across different countries; 2) Undertaking a cross-sectional study to quantify the prevalence of adherence to OHM in a group of patients in Saudi Arabia using a validated measure of adherence. An interview study on a subset of these patients then explored in detail Type 2 diabetic patients' beliefs and attitudes towards their OHM regimen, including factors which helped or hindered their medication taking behaviour. The systematic review included 37 studies. It showed that the level of OHM adherence varied widely across all measures: 36% to 95% when dispensing records were used, 37% to 98% with self-report, and 17% to 97% with pill counts. The term 'adherence' was most commonly used. There was no identified studies assessing OHM adherence in Saudi Arabia. The cross-sectional study showed that the level of OHM adherence was 40%, Lower adherence was associated with patients of younger age (OR, 1.084; 95% CI, 1.056-1.112), individual taking a higher number of non-OHM (OR, 0.848; 95% CI, 0.728-0.986) and having a higher HbA1c level (OR, 0.808; 95% CI, 0.691-0.943). The interview study identified several factors affecting OHM adherence using a validated theoretical framework. Facilitators of OHM adherence were OHM scheduling, knowledge about OHM, knowledge on other relevant behaviours such as diet and physical activity, knowing how to take OHM appropriately and how to manage hypoglycaemia. In addition, OHM adherence was facilitated by beliefs of preventing diabetic complications, avoiding insulin injections, achieving an improved quality of life, accepting diabetes, being optimistic about the future, and having high self-confidence. Conversely, barriers to OHM adherence were forgetfulness, cognitive overload, lack of knowledge of sexual health implications of OHM, and knowledge of OHM side effects or drug-drug interactions. Furthermore, side effects of OHM such as weight gain or hypoglycaemia, knowing how to measure blood sugar, feeling no symptoms, and having many medications to take were additional barriers to OHM adherence. The MASA study also showed that there are several social- and physical-related factors affecting OHM adherence such as the patient-physician relationship and perceived family support. The work in this PhD suggests that targeting suboptimal OHM adherence behaviour needs to be done in a comprehensive manner. The key benefit is to provide future researchers with a comprehensive range of factors that can be targeted when defining targets for an intervention(s). Further systematic intervention development and testing is required to choose and prioritise the most promising interventions to improve OHM adherence.

Finally, the pharmacodynamic effects of propranolol powder formulation with different buffering were carried out in two healthy male subjects. The maximal reduction in heart rate was found at the saliva pH of 7.6, which corresponded to the pHmax of propranolol. A buffered propranolol sublingual tablet was then prepared to achieve the saliva pH around 7.6. The preliminary investigation confirmed that the sublingually administrated buffered propranolol tablet produced a faster and more pronounced heart rate reduction than the non-buffered commercial propranolol tablet. / Firstly, the use of the HO-1-u-1 cell culture for screening sublingual drug delivery was validated. The cells were seeded on cell culture inserts. The integrity of cell layers, inter-passage variation and directionality were assessed by measuring the resistance and the permeability of standard markers, beta-blockers and calcium channel blockers. The effect of pH, osmolarity and a permeation enhancer (GDC) were also studied. The results showed that HO-1-u-1 cells grown on inserts formed stratified and epithelial-like structure that preserved the typical histological feathers of the normal human sublingual epithelium. The maximal integrity was reached in 23 days. The Papp of beta-blockers and calcium channel blockers ranged from 2.89+/-0.17 x 10 -6 cm/s to 6.37+/-0.37 x 10-6 cm/s. The permeability of selected beta-blockers under different pH, osmolarity and GDC revealed that enhancing effects were significant for hydrophilic compounds but less for lipophilic compounds. / Secondly, fresh porcine sublingual mucosa was prepared and compared to the cell line model. Good correlations were obtained for both the Papp of beta-blockers and the enhancement ratios of pH and GDC between the two models. / The aims of the present study are (1) to develop and validate a human sublingual epithelial cell line model and (2) to demonstrate the application in sublingual development of cardiovascular drugs. / Thirdly, the steady-state flux (Jss) at various pH levels were measured. Results show that saturated propranolol solution at pH 7.0--7.6 resulted in a much higher Jss than the solution at other pHs. These data led to the development of theoretical equations for predicting the optimum pH (pHmax) for ionizable compounds. The calculation fitted well with the experimental data. / Wang Yanfeng. / Advisers: Moses S. S. Chow; Zhong Joan Zuo. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 184-). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Abstract not available

Magister Curationis - MCur / Medication errors can result in harm and death, for which nurses are legally liable. The administration of medication by nurses can be improved through education and training to avoid medication errors in future. The study aimed to investigate fourth year Bachelor of Nursing students’ perceptions regarding the clinical learning opportunities and their competence in the administration of oral medication in a general hospital. A quantitative cross-sectional descriptive design was employed. The all-inclusive sample constituted 176 fourth year Bachelor of Nursing students. A total of 125 respondents completed the self- report questionnaires. Descriptive statistics were produced through data processing and univariate and bivariate analysis using of SPSS version 22. The study’s findings show that most of the 125 respondents were placed in a medical (92%, 115) and surgical ward (86.4%, 108). However, a total of 59.2% (74) of the 125 respondents did not practice administration of oral medication on a daily basis. The majority of the respondents perceived themselves as competent in the administration of oral medication. However, only a total of 19.2% (24) of the 125 respondents perceived themselves as competent in all 42 skills required for the correct procedure of administration of oral medication. A negative correlation was found between total self-assessment of competence scores and total clinical placement scores. An observation study, using the check list, of the competence of nursing students in the administration of medication is recommended to exclude bias associated with self-assessment. The use of simulation is recommended to enhance the opportunities and competence of the students in the administration of oral medication to many patients.

Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies. The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that the permeability of model diffusants decreased significantly with an increase in the connective tissue layer. However, the epithelium offered a stronger barrier to permeation of all diffusants studied at mucosal thickness of up to 500 |tm. The epithelium acted as a stronger barrier for hydrophilic diffusants when compared to lipophilic diffusants. It was also observed that the permeability of model diffusants was significantly higher in the region behind lip when compared to the middle cheek region which is due to lower epithelial thickness in that region. Porcine buccal mucosa retained its integrity in Kreb's bicarbonate Ringer solution at 4 °C for 24 hours and many other storage conditions resulted in loss of epithelial integrity. Separation of epithelium from the underlying connective tissue by heat treatment, did not adversely affect its permeability and integrity characteristics. Influence of experimental temperature on the permeability of model compounds across porcine buccal mucosa was also investigated in vitro. An exponential relationship was observed between the apparent permeability and temperature. It was found that the activation energy of diffusion of the model compounds decreased linearly with increasing distribution coefficients across porcine buccal mucosa. This suggested that the buccal mucosa acted as a stronger barrier for diffusion of hydrophilic diffusants when compared to the lipophilic diffusants.

differential scanning calorimetric profile and the generation of much less intense and broader peaks in the powder X-ray diffraction pattern compared to beta-CD. FTIR analysis revealed significant physical interactions between CX oil and beta-CD in the granules, possibly due to complexation. Results from phase solubility measurements and proton nuclear magnetic resonance ( 1H-NMR) analysis of pure 3-butylidenephthalide (3-BDPH), a representative CX component, lend some support for the formation of a 1:1 stoichiometric inclusion complex between 3-BDPH and beta-CD. / Rhizoma chuanxiong (CX), the dried rhizome of Ligusticum Chuangxiong Hort. (Umbelliferae), has been extensively used in mainland China as a traditional herbal medicine for treating cardio-/cerebrovascular diseases and gynecological disorders. However, the active components in CX, which are predominantly essential oils, generally exhibit poor stability (mostly photo-oxidation), high volatility, low aqueous solubility, and extensive gut/hepatic metabolism, all of which can significantly reduce their oral bioavailability and therapeutic efficacy. The present project has investigated the feasibility of utilizing three formulation approaches to circumvent the aforementioned problems associated with the peroral delivery of CX (as crude oil mixture or individual components). / The first approach involved inclusion of CX oil in beta-cyclodextrin (beta-CD) as solid granules using a coprecipitation method optimized with the aid of an orthogonal study design. The resulting CX oil granules were colorless and odorless with a median particle size of 11.38mum; were stable to heat, light and moisture, and readily soluble in simulated gastric and intestinal fluids. The granules were largely amorphous, as evidenced by an absence of the melting endotherm for beta-CD in the formulation could be largely explicated by the complexation behavior and hydration properties of the two polymers blended in different weight percentages, as substantiated by turbidity measurement, viscosity determination and FTIR analysis of the pure polymer mixtures as well as swelling measurement of the formulated tablets. The sustained release behavior of 3-BDPH from the tablet was dependent on the relative proportion of the two polymers present, and could be similarly explained by the changes in hydration and complexation behavior of the polymers during the penetration of aqueous fluid into the tablet matrix. / The second approach involved incorporation of CX oil into surfactant micelles and liquid crystals as a self-emulsifying drug delivery system (SEDDS). An optimal formulation was developed through a judicial choice of excipients (lipids and surfactants/cosurfactant) and their proper combination in the correct proportions, as determined by the spontaneity of the emulsification process and the change in emulsion droplet size. The formulation was readily dispersible in water upon mild agitation, free from unpleasant odor, and stable in soft gelatin capsules for a storage period of at least 12 months under ambient condition. The optimal utilization of the lipid and surfactant blends in defined proportions in the formulation was further substantiated by interfacial tension determination and equilibrium phase analysis. / The third approach involved formulation of 3-BDPH (or crude CX oil) into a sustained-release buccoadhesive tablet, based on a systematic evaluation of the adhesive properties of two polymers (Carbopol 974P and hydroxypropyl methylcellulose K4M) used in the formulation. The adhesive properties of the formulation could be largely explicated by the complexation behavior and hydration properties of the two polymers blended in different weight percentages, as substantiated by turbidity measurement, viscosity determination and FTIR analysis of the pure polymer mixtures as well as swelling measurement of the formulated tablets. The sustained release behavior of 3-BDPH from the tablet was dependent on the relative proportion of the two polymers present, and could be similarly explained by the changes in hydration and complexation behavior of the polymers during the penetration of aqueous fluid into the tablet matrix. / Gao Yuan. / "April 2005." / Adviser: Albert H. L. Chow. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1585. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 193-223). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (Ph.D.(Nursing Science)) -- University of Limpopo, 2021 / Health literacy related to medication use or instructions is crucial to diabetes mellitus patients. The verbal or written instructions are given to diabetes mellitus patients regarding medication use is important to improve patient care, safety, and compliance to treatment. However, the information provided to diabetes mellitus patients regarding medication use is not known as they continue to experience complications. The study aimed to develop and implement an educational programme, to enhance health literacy on prescribed medication instructions among diabetes mellitus patients on treatment at Ga-Dikgale village clinics in Capricorn District, Limpopo Province. The objectives of the study were to explore the knowledge, and practices of diabetes mellitus patients on treatment. Thus, to describe the provided information regarding prescribed medication usage contained in the diabetes mellitus medication packaging, medicine leaflets, and prescriptions. Therefore, to also describe the effects of poor health literacy on prescribed medication instructions among diabetes mellitus patients on treatment at Ga- Dikgale village clinics in Capricorn District, Limpopo Province. Data were collected using a mixed-method approach and a mixed-method sampling technique was used to select 18 participants for the qualitative strand. Whereas, there were 137 respondents for the quantitative strand. Tesch’s proposed eight steps to analyse the data were adopted to analyse the qualitative data and SSPS version 25 was used for analysing quantitative data. The results showed the following findings: patients lack knowledge about diabetes as a disease, misinterpret medication instructions, and are noncompliant to the treatment. This non-compliance is intensified by negligence and poor comprehension of medication instructions. As a result, to help diabetes mellitus patients with compliance with diabetes treatment, ongoing implementation of the educational programme should be instituted. The Limpopo’s Department of Health has to offer in-service vii education to the health professionals, who dispense medications on the interpretation of medication instructions. The high school curriculum is ought to incorporate health literacy to prescribe medication instructions. / National Institute for the Humanities and Social Sciences (NIHSS) and South African Humanities Deans Association (SAHUDA)

Representing more than 50% of a worldwide pharmaceutical market of US$ 400 billions, oral drug delivery systems become naturally the focus of many studies. For almost half a century scientists have attempted to develop a theoretical model capable of predicting oral drug absorption in humans. From steady state or quasi-equilibrium models to complex and computationally intractable dynamic modeling approaches, numerous research efforts tried to address the problem of interest. Surprisingly though, no simple insightful first-principle-based dynamic modeling approaches have been reported in the literature. It is the purpose of the present work to provide a simple dynamic distributed-parameter modeling approach for performance monitoring of oral drug delivery systems. As a consequence of the complexity of the gastrointestinal tract, drug oral bioavailability is influenced by many different parameters. These parameters range from the compound's physicochemical properties, the physiological factors of the environment to other factors inherent in the drug form itself known as encapsulation factors. Physicochemical properties account for parameters such as drug stability, solubility or diffusivity. Furthermore, the environment, namely the gastrointestinal tract, influences the drug delivery process to the body with its pH, intestinal transit time and the different transport mechanisms that take place. From a chemical engineering point of view, the human body's anatomy can be analyzed and conceptually realized as a transport-reaction chemical system. Within the proposed modeling framework, the stomach is modeled as a non-ideal continuous-stirred tank reactor (CSTR) and the small intestine is the place where convection-diffusion occurs. The governing transport equations have been solved at steady state conditions in a small intestine represented by the lumen surrounded by its wall. The present work however develops a systematic dynamic first-principle-based distributed-parameter modeling framework where the time-dependent convection-diffusion-reaction model equations are analytically solved, offering the concentration profile in the small intestine lumen and in the wall from the moment the drug is administered until the complete absorption or disintegration of the drug particles. Once the modeling work is performed, a thorough and insightful sensitivity analysis can be conducted in order to assess the impact of the different process parameters on drug bioavailability.