Stability Studies On Reconstituted Amoxycillin-Clavulanic Acid Oral Suspension by HPLC Development and Quantification

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Amoxycillin has a broad spectrum of activity against a wide number of organisms. However its usage as mono-therapy for certain infections such as respiratory tract infections became ineffective due to the emergence of beta lactamase producing bacteria. Clavulanic acid was thus introduced as a protective agent for amoxycillin against such organisms. The two also have a synergistic effect although clavulanic acid on its own has no significant antibacterial action. The formulation of amoxycillin and clavulanic acid (Co – amoxiclav) for paediatric use comes in the form of an oral powder, which has to be reconstituted before administration. Concerns have been raised with regards to the appropriateness of the use of certain kinds of water such as treated tap water or any portable drinking water for that matter, in the reconstitution of oral powders such as that of co – amoxiclav into suspensions. Thus, a stability study was carried out on co – amoxiclav oral powder reconstituted with distilled water (the recommended choice), treated tap water and a commercial mineral water, under the standard storage condition of 2 - 8ºC. From the study, it was found that the three kinds of water, irrespective of their mineral or ionic content, did not have any significant detrimental effect on the stability of amoxicillin and clavulanic acid, as long as the oral suspension was stored in a refrigerator (2 - 8 ºC) throughout the duration of therapy (7 days). Thus, the above mentioned types of water can be conveniently used for the reconstitution of co – amoxiclav in our part of the world. Further analysis was carried out to ascertain the stability of amoxicillin and clavulanic acid in their oral suspension (reconstituted with distilled water) when stored in the refrigerator (2 - 8ºC) only on alternate days during the duration of therapy. It was found that both amoxicillin and clavulanic acid remained stable in spite of the inconsistency in their storage conditions. However, the standard storage temperature should be adhered to stringently to guarantee maximum therapeutic benefit. A simulation was carried out where co – amoxiclav oral suspension was kept in a bowl of water under normal room temperature and analysed. This also revealed that amoxicillin remained stable throughout the duration of therapy but clavulanic acid did not. To aid in the stability studies, a simple and cost effective High Performance Liquid Chromatographic method of assay was developed. The method made use of a reverse phase column of Phenomenex, Kromasil 5 (C8), 250 X 4.60mm 5 micron column with size 305334. The flow rate was 1ml/min and a UV detector was used to detect at a wavelength of 220nm.The mobile phase system comprised of Water, methanol and sodium acetate buffer pH 4.4 in the ratio of 60:15:20. The LOD and LOQ for amoxicillin were 0.00614%w/v and 0.0186%w/v respectively and the LOD and LOQ for clavulanic acid were 0.00126%w/v and 0.003818%w/v for respectively. In all three brands of co-amoxiclav were assayed including the innovator brand.
A Thesis submitted to The Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, In partial fulfillment of the requirements for the degree of Master of Philosophy in Pharmaceutical Chemistry,