Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability

YesIn order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs) may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs, carriers, or binders due to their good compactibility performanceSolid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under Grant No. 07/SRC/B1158

Foot-and-mouth disease sero-surveillance in Africa and vaccine matching

Foot-and-mouth disease virus (FMDV) was the first animal pathogen to be identified as a virus, and today, more than a century later, it remains at the forefront of major animal diseases. It is a very contagious disease and affects cloven-hoofed domestic and wild animals, mostly cattle, swine, sheep, goats and buffaloes. To be able to advice on the best control measures in Africa, information on transmission of FMDV, circulating FMDV topotypes and strains in Africa and how to match vaccines to circulating outbreak virus strains is essential. In this thesis these issues are addressed. The research work described in this thesis has been performed for three important aspects. The first was to get an overview of the role that animal husbandry, trade and wildlife have on the transmission of FMD virus and to provide a scientific basis for different FMD control measures in Africa. On the same track, two surveillance studies on FMD were carried out to know the level of sero-prevalence and identify the serotypes in cattle in Eritrea. The second was to determine which serological test method is best to be used to test cross-reactions in serology and addresses the inherent variability of the relationship coefficient (r1-value). To this end we analysed the cross-reactions in serology using serum samples from cattle vaccinated with 10 different FMDV serotype A strain vaccines using three serological test methods (virus neutralization test, neutralization index test and the liquid phase blocking ELISA). The third was to investigate whether the formulation of using different adjuvants, antigen composition, antigen payload and administration route of an FMD vaccine had any influence on the breadth of the antibody response in cattle. The review of reported outbreaks shows that substantial diversity of the circulating FMDV serotypes and topotypes is linked to the complexity of the livestock husbandry system, the marketing structure, and livestock-wildlife interface reflecting the significant influence on the risk of transmission of the virus. The sero-surveillance studies show that serology can give indications of virus circulation not detected by agent surveillance. The comparisons of tests used for antigenic matching shows that the LPB-ELISA is the best test for detecting antigenic differences between FMDV strains. Our study on vaccine formulation and application shows that breadth of the antibody response depends mainly on the vaccine strain; we therefore propose that, for vaccine preparation, only FMD virus strains are selected that, among other important characteristics, will induce a wide antibody response to different field strains. For Africa control of FMDV by vaccination seems the best option, as control of animal movement will be difficult. Use of broadly cross-protective vaccines for FMD is recommended as variant viruses could be introduced from neighbouring countries/regions. A vaccination strategy has still a number of challenges, among others vaccine quality control and quality control of the vaccination campaign. We believe that despite the enormous investments needed in the long run, FMDV control in Africa would improve national and regional economies and food security and protect livelihoods

Determinants of immediate complications of abortion: A study done in Mekane Hiwet Maternity Hospital.

Objective: to identify the main determinants associated with immediate complications of abortion. The determinants (factors) studied were: delay in arrival to the hospital, delay in starting treatment, type of onset of abortion (induced or spontaneous), gestation at onset of abortion, age, marital status, literacy and parity. Design: A cross sectional descriptive study Setting: Mekane Hiwet Maternity Hospital, Asmara, Eritrea Subjects: 368 patients admitted to the hospital with the diagnosis of abortion during a 3-month study period (June 1st to August 31st of 2003) Outcome measure: the proportion of early complications of abortion namely, heavy bleeding and infection. Results: The main determinant factors identified to be associated with early complication of abortion were: inducing the abortion (50% versus 21%), advanced gestational age at onset of abortion (31.9% versus 20.5%) and being unmarried (38.25 versus 20.2%). Furthermore it was found that when abortion was induced, it was being induced at an advanced gestational age making a deadly combination of the two risk factors. Conclusion: The finding is in consistency with most studies on abortion done in Africa calling for a remedial action to be taken to avert the need of inducing abortion unsafely and give the necessary post abortion care for the victims

TB-HIV co-infection in Eritrea

We assessed the prevalence of tuberculosis (TB) human immunodeficiency virus (HIV) co-infection and identified risk factors for HIV infection in smear-positive TB patients diagnosed by the TB programme in Eritrea. Of 365 notified TB patients, 220 (60.3%) could be traced and provided a blood sample that was tested. Of these, 26 (11.8%, 95%CI 7.6-16.1) were HIV-infected. Risk factors were age, urban residence and schooling level. The data indicate that, starting with the urban areas, it is time for Eritrea to introduce HIV testing of all TB patient

Exploring variability across cooperatives : economic performance of agricultural cooperatives in northern Ethiopia

The number of agricultural cooperatives increased quickly in Ethiopia since the 1990s. While many papers studied the impact of membership of Ethiopian cooperatives, not much is known on their performance. This study takes a cooperative-level perspective which is unique in an African context. It compares the economic performance proxied by sales revenue and profit of a wide range of agricultural cooperatives in northern Ethiopia. Data were collected from 511 agricultural cooperatives in 12 districts of Tigray. The contributing factors of the performance are analyzed with Ordinary Least Squares regression (OLS) and Heckman selection models. Our results underscore the importance of membership size, total assets, presence of conflict among members, and union membership. Chairperson characteristics and the internal organization of a cooperative seem to be less correlated to performance