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Title of Thesis

Major Muhammad Afzal, AEC
Institute/University/Department Details
Department of Pharmaceutical Chemistry/ University of Karachi
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
cephradine, metal interactions, cephalosporin, staphylococci, penicillin

The research work comprises of interaction studies of cephradine with essential metals and non metals, antacids and antagonists.

Cephradine is included among the first generation cephalosporin which is active against a wide range of gram positive and gram negative bacteria including penicillinase producing staphylococci.

Since the presence of complexing ligand may affect the bioavailability of a metal in the blood or tissues, therefore, in order to study the probable interaction of cephradine with essential and trace elements present in human body, cephradine has been interacted with magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and cadmium metal salts in vitro. All the reaction conditions were simulated to natural environments.

The studies were carried out in simulated gastric and intestinal juices having pH 1 and 7.4 in variable ratios of drug and metal both at room as well as at elevated temperature conditions. It has been observed that almost major proportion of drug is complexed with the metals.

The effect of pH on drug-metal complexation was also studied. These studies were carried out in buffers ranging from pH 1-9 and variable ratios of drug and metal. It has been observed that cephradine interacts with metals at all pH except for neutral pH giving minimum absorption of drug in presence of all metals. The stability constant of these complexes were determined in order to evaluate their possible in vivo implications.

In order to investigate the number of metal ions involved in the complexation with cephradine, complexes were synthesized and structures elucidated by exploiting various spectrophotometric techniques. The infrared and ultraviolet studies of these complexes were carried out and compared with ligand. Magnetic susceptibility studies of these complexes were also carried out showing their paramagnetic behavior. From the infra red studies and elemental analysis of the complexes it has been shown that the drug molecule serves as a bidentate ligand coordinating through both its β-lactam COO- and nitrogen and the metal having a square planar or octahedral geometry.

Antacids and H2-receptor antagonists are commonly used in patients complaining of GI irritations. The behavior of these antacids as simethicone, magldrade, magnesium carbonate, magnesium hydroxide, magnesium trisilicate, sodium bicarbonate and aluminium hydroxide, and antagonists as cimetidine, ranitidine, famotidine and nizatidine in presence of cephradine was studied by using standard dissolution apparatus. The percentage of drug available was then found through computer methods. It has been found that maximum drug drug interaction takes place during the simultaneous administration of both the drugs.

To evaluate the changes in microbiological activity of cephradine after complexation, antibacterial studies were carried out by observing the changes in MIC (minimum inhibitory concentration) of the complexes and compared with the parent drug by measuring the zone of inhibition of complexes and compared with the parent cephalosporin against both gram positive and gram negative organisms. For MIC observation, serial dilution method was employed and zone series were determined by disk diffusion method. Our investigations reveal that formation of complexes results in decrease in antibacterial activity of cephradine and MIC values are increased

Download Full Thesis
2330.15 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
73.73 KB
2 1 Introduction 5
608.14 KB
  1.1 Cephalosporins 5
  1.2 Cephradine 19
  1.3 Trace And Essential Elements 38
  1.4 Antacids 57
  1.5 Drug Acting On H 2 -Receptors 59
  1.6 Drug Interactions 67
  1.7 Objectives Of Present Work 68
3 2 Experimental 70
176.24 KB
  2.1 Materials 70
  2.2 Methods 72
4 3 Results And Discussion 91
1505.15 KB
  3.1 Discussion 91
  3.2 Methods Of Analysis 92
  3.3 Cephradine Metal Interaction Studies 94
  3.4 Cephradine Antacid Interactions 204
  3.5 Cephradine H 2 -Receptor Antagonists Interactions 211
  3.6 Synthesis Of Cephradine Metal Complexes 273
  3.7 Antibacterial Studies 285
  3.8 Annexure I 297
5 4 References 300
342.04 KB