PP  Vol.5 No.1 , January 2014
The Quality and in Vitro Efficacy of Amoxicillin/Clavulanic Acid Formulations in the Central Region of Ghana
Abstract: Aim: To assess the quality and in vitro efficacy of five brands of amoxicillin/clavulanic acid tablet, suspension and injectable preparations selected from pharmacies in the Central Region of Ghana. Method: Using a Stratified Representation Sampling method, forty preparations (tablets, suspensions and injectable powders) containing amoxicillin and clavulanic acid were sampled from nine different locations within the Central Region of Ghana. To determine drug quality, several procedures, namely, content assay, disintegration and dissolution testing were employed. In vitro drug efficacy was determined by comparing the Minimum Inhibitory Concentrations (MIC’s) obtained with published values. Results: All tablets passed the disintegration test, with disintegration time ranging between six (6) and fifteen (15) minutes. Analyses of all the tablets for drug content showed 100% failure (14 out of 14) for amoxicillin and 14% failure (2 out of 14) for clavulanic acid. Injectable formulations showed similar results. All four (4) samples analyzed for content failed the amoxicillin content assay (0 out of 4) but all passed clavulanic acid assay (4 out of 4). For tablet dissolution tests, there was a 93% (13 out of 14) pass rate for both amoxicillin and clavulanic acid. Content analysis of all suspension formulations involved twenty-two (22) samples from five (5) brands. Only 41% (9 out of 22) passed for both amoxicillin and clavulanic acid. All the other samples failed for either amoxicillin, clavulanic acid or both. Results obtained from drug quality tests were confirmed by in vitro efficacy tests against selected microorganisms. Conclusion: The samples were therefore not of good quality, since content assay is the most crucial test. It is hypothesized that this is due to poor storage conditions, and recommendations, such as air conditioning and more structured procedures along the supply chain, are put forward to counteract this.
Cite this paper: H. Nettey, G. Allotey-Babington, P. Debrah, O. Adi-Dako, M. Shaick, I. Kintoh, F. Arnansi, M. Nyagblordzro and M. Holison, "The Quality and in Vitro Efficacy of Amoxicillin/Clavulanic Acid Formulations in the Central Region of Ghana," Pharmacology & Pharmacy, Vol. 5 No. 1, 2014, pp. 49-60. doi: 10.4236/pp.2014.51009.

[1]   M. E. Arroliga and L. Pien, “Penicillin Allergy: Consider Trying Penicillin Again,” Cleveland Clinic Journal of Medicine, Vol. 70, No. 4, 2003, pp. 313-314.

[2]   C. Walsh, “Molecular Mechanisms That Confer Antibacterial Drug Resistance,” Nature, Vol. 406, No. 6797, 2000, pp. 775-781.

[3]   A. Ashnagar and N. G. Naseri, “Analysis of Three Penicillin Antibiotics (Ampicillin, Amoxicillin and Cloxacillin) of Several Iranian Pharmaceutical Companies by HPLC,” Journal of Chemistry, Vol. 4, No. 4, 2007, pp. 536-545.

[4]   A. Sullivan, C. Edlund and C. E. Nord, “Effect of Antimicrobial Agents on the Ecological Balance of Human Microflora,” The Lancet Infectious Diseases, Vol. 1, No. 2, 2001, pp. 101-114.

[5]   C. M. Kaye, A. Allen, S. Perry, M. McDonagh, M. Davy, K. Storm, N. Bird and O. Dewit, “The Clinical Pharmacokinetics of a New Pharmacokinetically Enhanced Formulation of Amoxicillin/Clavulanate,” Clinical Therapeutics, Vol. 23, No. 4, 2001, pp. 578-584.

[6]   S. M. Drawz and R. A. Bonomo, “Three Decades of βLactamase Inhibitors,” Clinical Microbiology Reviews, Vol. 23, No. 1, 2010, pp. 160-201.

[7]   M. Coll, J. Frau, B. Vilanova, J. Donoso, F. Munoz and F. G. Blanco, “Theoretical Study of the Alkaline Hydrolysis of a Bicyclic Aza-β-Lactam,” The Journal of Physical Chemistry B, Vol. 104, No. 47, 2000, pp. 11389-11394.

[8]   World Health Organisation (WHO), “Quality Assurance of Pharmaceuticals: A Compendium of Guidelines and Related Materials,” Vol. 2, Geneva, 2004.

[9]   S. K. Opuni, “Alert: Osons Chemists, Roxin Ghana Import Fake Medicines from Ghana,” My Joy Online, 2013.

[10]   S. Ayim, “List of Hospitals and Pharmacies in the Central Region of Ghana as recorded by the Regional Health Directorate,” Personal Interview, 2012.

[11]   World Health Organisation (WHO), “The International Pharmacopoeia,” 4th Edition, 2nd Supplement, Geneva, 2008.

[12]   Clinical and Laboratory Standards Institute, “Performance Standards for Antimicrobial Disk Susceptibility Test; Approved Standard,” CLSI Document M02-A10, 10th ed. 2009.

[13]   British Pharmacopoeia Commission, “British Pharmacopoeia 2013,” Renouf Publishing Company Limited, UK, 2013.

[14]   S. Sengaloundeth, M. D Green, F. M. Fernández, Ot. Manolin, K. Phommavong, V. Insixiengmay, C. Y. Hampton, L. Nyadong, D. C. Mildenhall, D. Hostetler, L. Khounsaknalath, L. Vongsack, S. Phompida, V. Vanisaveth, L. Syhakhang and P. N. Newton, “A Stratified Random Survey of the Proportion of Poor Quality Oral Artesunate Sold at Medicine Outlets in the Lao PDR—Implications for Therapeutic Failure and Drug Resistance,” Malaria Journal, Vol. 8, 2009, p. 172.

[15]   P. N. Newton, M. D. Green, D. C. Mildenhall, A. Plancon, H. Nettey, L. Nyadong, D. M. Hostetler, I. Swamidoss, G. A. Harris, K. Powell, A. E. Timmermans, A. A. Amin, S. K. Opuni, S. Barbereau, C. Faurant, R. C. W. Soong, K. Faure, J. Thevanayagam, P. Fernandes, H. Kaur, B. Angus, K. Stepniewska, P. J. Guerin and F. M. Fernández, “Poor Quality Vital Anti-Malarials in Africa—An Urgent Neglected Public Health Priority,” Malaria Journal, Vol. 10, 2011, p. 352.

[16]   E. A. Nyarko and H. Nettey, “Quality Assessment of Artemether/Lumefantrine Tablets Sampled from Pharmacies in Accra, Using the MVHimagePCv8.exe Color Software,” Pharmacology & Pharmacy, Vol. 4, 2013, pp. 567-572.

[17]   J. Feng, X. Zhana, S. Qiaob, C. Wub and L. Xiaob, “A Mathematical Model for Calculating the Shelf Life of Ascorbic Acid Solution under Given Conditions,” Drug Development and Industrial Pharmacy, Vol. 38, No. 3, 2012, pp. 264-270.

[18]   D. Q. Craig, “The Mechanisms of Drug Release from Solid Dispersions in Water-Soluble Polymers,” International Journal of Pharmaceutics, Vol. 231, No. 2, 2002, pp. 131-144.

[19]   S. A. Qureshi and J. Shabnam, “Cause of High Variability in Drug Dissolution Testing and Its Impact on Setting Tolerances,” European Journal of Pharmaceutical Sciences, Vol. 12, No. 3, 2001, pp. 271-276.