الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The efficacy of generics compared to corresponding brand has been a point of focus in pharmaceutical research for several decades. However, little attention has been given to possible variation in quality and efficacy within the same brand depending on production site, storage condition, manufacturing condition, transportation and product specification demanded in different geographical locations. The present thesis addresses this issue focusing on a drug widely used in Egypt for chronic disorders.
Possible factors contributing to variations in the quality of brand products under license in different countries include formulation factors, storage conditions, manufacturing condition, transportation as well as quality of raw materials including the drug substance and excipients.
In the Introduction to the thesis, a survey of prevalence of chronic diseases, particularly thyroid diseases was conducted and reports of inequivalence of brand products worldside were reviewed. In view of the complaints of the inconsistant efficacy of brand products under licence from different countries, it was important when planning the present thesis to study the in vitro performance and clinical efficacy of multisource brand products for one of the narrow therapeutic index drugs, namely levothyroxine sodium available in Egypt as Eltroxin and Euthyrox tablet brands.
Levothyroxine sodium (T4) is the standard of care in the treatment of hypothyroidism. The narrow therapeutic index of thyroid replacement therapy with T4 is well recognized. Small variations in the available amount of active T4 can affect both efficacy and safety, as they may result in clinical or subclinical hypothyroidism or hyperthyroidism. Careful titration is required to adjust thyroid stimulating hormone (TSH) levels to within normal limits for each individual. For these reasons, it was thought useful to select and evaluate multisource levothyroxine sodium brand products marketed in Egypt.
The present thesis aimed to document and assess possible variability in pharmaceutical attributes and clinical efficacy of different multisource levothyroxine sodium tablet brands marketed in Egypt, and to investigate possible causes of the observed variability.
The studies, carried out in the four chapters were designed to allow: Comparing the pharmaceutical quality of tablet brands manufactured in different countries under two licensing trademark and sold in Egypt.
Criteria for comparison of tablets include drug content, content uniformity, dissolution rate and NIR.
Monitoring possible changes in dissolution rate and in drug content during the shelf life of the tablets as an indicator of pharmaceutical stability.
Comparing the clinical efficacy of the selected tablets in patients. Correlating the pharmaceutical data with pharmacodynamic activity.