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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Establishing quality profiles for 3D printed tablets loaded with different poorly water-soluble substances.

Matossian, Lilit January 2024 (has links)
Introduction: Integrating 3-dimensional (3D) printing with lipid-based formulation (LBF) is impacting pediatric pharmaceutical manufacturing by enabling personalized oral dosage forms tailored to children's specific needs. Serious challenges are created by manipulating conventional adult dosages to produce suitable dosages for the pediatric population. The study explores an emulsion gel with two model lipophilic drugs, Aprepitant and Irbesartan, using semi-solid extrusion (SSE) as a 3D printing method to produce patient-centered dosages. Method: The solubility of the two model drugs in the studied LBF type IIIA – MC was determined using the shake-flask method combined with High-Performance Liquid Chromatography with Ultraviolet Detection (HPLC-UV) analysis. Once determined, LBF was loaded with 90% of the soluble drug amount to later produce the emulsion by mixing the drug-loaded LBF with Milli-Q water. The emulsion gel was produced as the next step by adding three different polymers to the emulsion. The three polymers were Methylcellulose Methocel (A4C), Methylcellulose Methocel (A4M), and Sodium Crosscarmellose (AcDiSol). Lastly, tablets were 3D-printed using a BIO X 3D printer with a pneumatic printhead. The tablets were vacuum-dried and analyzed for mass and content uniformity, and disintegration time.  Results: The thermodynamic solubility of Aprepitant in LBF IIIA – MC was determined to be 11.30 mg/g while the solubility of Irbesartan was 4.08 mg/g. The produced tablets contained lower concentrations of the drugs compared to the traditional dosages available on the market. The 3D-printed tablets passed the European Pharmacopeia requirements for mass and content uniformity, and disintegration time.  Conclusion: The study showed justified results indicating the emulsion gel can be used to produce tablets loaded with different poorly water-soluble drugs. All characterization studies done on the 3D-printed tablets carried out according to the European Pharmacopeia guidelines showed correct mass and content uniformity together with reasonable disintegration time. This suggests that the emulsion gel has the potential to be used to produce tablets loaded with any other lipophilic drug, potentially multiple drugs loaded at the same time.
2

Pharmacogenomics of Antihypertensive Treatment & Clinical Pharmacological Studies of Digoxin Treatment

Hallberg, Pär January 2005 (has links)
In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele. In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p<0.001), which could be of importance since an SDC >1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders). In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.
3

Bedeutung der Blockade des lokalen Angiotensinsystems für die chronisch progrediente Niereninsuffizienz im Rahmen der Alport-Nephritis / Significance of Blockade of the Local Angiotensin System for Chronic Progressive Renal Insufficiency in context of alport nephritis

Bemme, Sebastian 03 September 2012 (has links)
No description available.

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