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Formulation Development of Antibiotics for ASTar Antimicrobial Susceptibility of Gram-Positive Bacteria
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2023 (English)Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Q-Linea, a diagnostic company, has developed ASTar®, a fully automated instrument that enables rapid Antibiotic Susceptibility Testing (AST). ASTar can report the Minimum Inhibitory Concentration (MIC) of a wide number of antibiotics in approximately 6 hours, directly from a positive bacterial blood culture. The ASTar kit, which is currently on the market, is designed to analyze gram-negative bacteria (ASTar BC G- kit) and consists of the sample preparation Cartridge, the Frozen Insert, and the G- AST Disc. This thesis is reporting exploratory work targeting to use of antibiotics targeting gram-positive bacteria in the AST disc for ASTar.  In about 50% of all cases of positive blood cultures from patients with suspected sepsis, gram-positive bacteria are isolated. These bacteria are generally targeted with other antibiotics than those that are on the current BC G- kit Disc for use with ASTar. Understanding the formulation operations of the drugs and their stability during manufacturing and storage is required for effective antibiotic susceptibility testing (AST). The objective of this thesis is to investigate formulations for linezolid, tetracycline, imipenem, daptomycin, dalbavancin, and erythromycin and clindamycin in combination, where the drugs remain stable during disc manufacturing and storage. Also, a precise minimum inhibitory concentration (MIC) of antibiotics must be achieved by analyzing the disc used in the ASTar. The formulations of the compounds were studied for their physical and chemical stability, such as the solubility of the drugs in solution using high-performance liquid chromatography (HPLC). The excipient type and concentration were selected based on broth microdilution experiments and HPLC analysis. The selected formulations were used in manufacturing the discs using the process developed in-house at Q-linea. The drug concentrations in the discs were determined by HPLC, and the MIC values were determined by the ASTar instrument. The drugs solubility and stability were improved by using appropriate excipients that imparted kinetic and thermodynamic stability and were confirmed to be suitable for the ASTar instruments, revealing that the MIC results of the drugs were in agreement with concentrations determined by chemical analysis. The formulations developed in this project are valuable for the future disc. Revealing that the robust performance in the ASTar and stability during storage are key for considering these formulations.

Place, publisher, year, edition, pages
2023. , p. 24
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-505670OAI: oai:DiVA.org:uu-505670DiVA, id: diva2:1771683
External cooperation
Q-linea
Subject / course
Pharmacy
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2023-06-22 Created: 2023-06-20 Last updated: 2023-06-22Bibliographically approved

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