Chemical, biopharmaceutical and microbiological profiles of ciprofloxacin tablets in the Nigerian market
Abstract
Background: The number of ciprofloxacin hydrochloride brands in the Nigerian market is continuously increasing; hence, there is need to establish their bioequivalence in the interest of public health. This study assessed the chemical, biopharmaceutical, and microbiological profile of thirty brands of ciprofloxacin (500 mg) tablets in Nigerian market.
Method: Quality parameters evaluated include weight uniformity, thickness and diameter, hardness, friability, disintegration, dissolution, identity, and antibacterial profile. Content of active ingredients was determined by a slightly modified and validated HPLC method.
Results: Results of thickness, diameter, and hardness tests of all the brands fell within acceptable limits. The percentage of brands within acceptable range for weight uniformity, friability, disintegration, dissolution, and active ingredient are 86.67, 96.67, 93.33, 26.67, and 93.33% respectively. About 87% of the tested generic version of ciprofloxacin demonstrated in-vitro antibacterial bioequivalence to the reference drug. The abysmal low dissolution rate of 26.67 % is a source of concern as it suggests a potential poor bioavailability of the active ingredient of these drugs.
Conclusion: The failure of a large portion of the tested brands may be due to deliberate counterfeiting, failure of current good manufacturing practices (cGMP) by manufacturers or poor handling by wholesalers/retailers. The study therefore recommends effective post marketing surveillance and enforcement of cGMP by the concerned regulatory agency in Nigeria.
Keywords: Bioequivalence, ciprofloxacin, quality, GMP, drug faking, and infectious diseases
Résumé
Contexte: Le nombre de marques de chlorhydrate de ciprofloxacine sur le marché nigérian ne cesse d’augmenter; par conséquent, il est nécessaire d’établir leur bioéquivalence dans l’intérêt de la santé publique. Cette étude a évalué le profil chimique, biopharmaceutique et microbiologique de trente marques de comprimés de ciprofloxacine (500 mg) sur le marché nigérian.
Méthode: Les paramètres de qualité évalués comprennent l’uniformité du poids, l’épaisseur et le diamètre, la dureté, la friabilité, la désintégration, la dissolution, l’identité et le profil antibactérien. La teneur en ingrédients actifs a été déterminée par une méthode HPLC légèrement modifiée et validée.
Résultats: Les résultats des tests d’épaisseur, de diamètre et de dureté de toutes les marques se situaient dans des limites acceptables. Le pourcentage de marques dans la plage acceptable pour l’uniformité du poids, la friabilité, la désintégration, la dissolution et l’ingrédient actif est de 86,67, 96,67, 93,33, 26,67 et 93,33% respectivement. Environ 87% de la version générique testée de la ciprofloxacine a démontré une bioéquivalence antibactérienne in vitro avec le médicament de référence. Le faible taux de dissolution abyssal de 26,67% est une source de préoccupation car il suggère une mauvaise biodisponibilité potentielle de l’ingrédient actif de ces médicaments.
Conclusion: L’échec d’une grande partie des marques testées peut être dû à une contrefaçon délibérée, à un échec des bonnes pratiques de fabrication actuelles (cGMP) par les fabricants ou à une mauvaise manipulation par les grossistes / détaillants. L’étude recommande donc une surveillance post-commercialisation efficace et l’application des BPF par l’organisme de réglementation concerné au Nigéria.
Mots clés: Bioéquivalence, ciprofloxacine, qualité, BPF, contrefaçon de médicaments et maladies infectieuses
Correspondence: Dr. Olufunmilayo E. Adejumo, Department of Pharmaceutical and Medicinal Chemistry, Olabisi Onabanjo University, Sagamu, Nigeria. E-mail: funmilayo@yahoo.co.uk
References
WHO in World Health Report, World Health Organization, Geneva. 2002.
Vos T, Lim SS, Abbafati C, Abass M, Abbasifard M et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019, The Lancet 2020; 396: 1204-1222.
Research and Markets. Antibiotics: Global markets to 2023. Available from: https://www.research andmarkets.com/research/k9z38f/global. Accessed 07/07/2020
Drusano GL, Standiford HC, Plaisance K, et al. Absolute oral bioavailability of ciprofloxacin. Antimicrob Agents Chemother 1986; 30: 444–446.
The Merck Index. 14th ed. Whitehouse station, NJ. Merck & Co., INC. 2006; pp.386, 1624,
“Ciprofloxacin Hydrochloride”. The American Society of Health-System Pharmacists. Bethesda MD. Ciprofloxacin hydrochloride Drug Information Available from: https://www.ncbi.nlm.nih.gov/mesh/68002939. Accessed 27/09/2020
Bertino J. The safety profile of the fluoroquinolones. Clin Ther 2000; 22:798-817
Samanidou V, Demetriou C and Papadoyannis I. Direct determination of four fluoroquinolones, enoxacin, norfloxacin, ofloxacin and ciprofloxacin, in Pharmaceuticals and blood serum by HPLC. Anal Bioanal Chem 2003; 375: 623-629.
Shi LW, Han S, Zhao YL and Guan XD. Safety Profile of Fluoroquinolones: analysis of Adverse Drug Reactions in Relation to Consumption data Using Pharmacovigilance Database in Hebei, China. Value in Health 2015; 18: A1–A307
Cipro (Ciprofloxacin): Uses, dosage, side effects, drug interactions, warning and precautions, overdosage and contraindications, clinical pharmacology, medication guide. Available from: https://www.rxlist.com/cipro-drug.htm Accessed 25/05/2021. Fasugba O, Gardner A, Mitchell BG, Mnatzaganian G. Ciprofloxacin resistance in community- and hospital-acquired Escherichia coli urinary tract infections: a systematic review and meta-analysis of observational studies. BMC Infect Dis. 2015;15:545.
Kaplan YC and Koren G. Use of ciprofloxacin during breastfeeding. Can Fam Physician. 2015; 61(4):343-344. .
Kaguelidou F, Turner MA, Choonara I and Jacqz-Aigrain E. Ciprofloxacin use in neonates: a systematic review of the literature. Pediatr Infect Dis J. 2011; 30(2):e29-37.
Cozzani E, Chinazzo C, Burlando M, Romagnoli M and Parodi A. Ciprofloxacin as a Trigger for Bullous Pemphigoid: The Second Case in the Literature. Am J Ther. 2016; 23(5):e1202-1204.
Thai T, Salisbury BH and Zito PM. Ciprofloxacin. StatPearls Publishing LLC, 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535454/ Accessed 25/05/2021
Adepoju-Bello AA, Coker HAB and Abioye AO. Quinolones: A review. Nig J Pharm 2007; 40: 58-63.
Ngwuluka NC, Lawal K, Olorunfemi PO and Ochekpe NA. Post-market in vitro bioequivalence study of six brands of ciprofloxacin tablets/caplets in Jos, Nigeria. Scientific Research and Essay 2009; 4: 298-305.
Ilupeju TO, Oladeinde EO, Olaniyi AA and Amosu M. Bioequivalence study of multi-sourced (generic) co-trimoxazole tablets in human urine. In: Olaniyi AA, Babalola CP, Oladeinde EO, Adegoke AO Eds. Towards better quality assurance of Drugs in the 3rd Millennium- Biopharmaceutical methods in drug quality assurance. 1st ed. Ibadan, Nigeria: Omoade Printing Press, 2001.
Almuzaini T, Choonara I and Sammons H. Substandard and counterfeit medicines: A systematic review of the literature. BMJ 2013; 3: e002923. Available from: https://www.researchgate.net/publication/255975639_ [cited: 27th September 2020].
World Health Organization. WHO Global Surveillance and Monitoring System for substandard and falsified medical products. Geneva: World Health Organization, 2017.
Giri TK, Parveen N, Thakur D, et al. In vitro evaluation of commercially available enteric coated tablet containing diclofenac sodium. Int J Res Pharmaceut and Biomed Sci 2012; 3: 875-881.
Ahmed MM, Farhat F, Ansari MJ, et al. Equivalent assessment of Ciprofloxacin tablets Available in KSA: A post market surveillance study for cost effective treatment. J Pharm Sci Res 2016; 8: 13-18.
Minyeto D. In Vitro Comparative evaluation of the quality and pharmaceutical equivalence of selected generic ciprofloxacin hydrochloride tablet brands marketed in Kenya. M.Sc. Thesis. Kenya: University of Nairobi, 2014.
Kahsay G,G. and Egziabher AG. Quality assessment of the commonly prescribed antimicrobial drug, ciprofloxacin tablets, marketed in Tigray, Ethiopia. Momona Ethiopian J Sci 2010; 2: 93-107.
Okonkwo TJ, Afieroho EO, Odigwe A and Osadebe PO. Assessment of the quality control parameters of five brands of ciprofloxacin hydrochloride caplets in Nigeria. J Pharm Biores 2006; 3: 83-88
Adegbolagun OA, Olalade OA and Osumah SE. Comparative evaluation of the biopharmaceutical and chemical equivalence of some commercially available brands of ciprofloxacin hydrochloride tablets. Trop J Pharm Res 2007; 6: 737-745.
Mu’az J, Gazali LK, Sadiq GU and Tom GM. Comparative in vitro evaluation of the pharmaceutical and chemical equivalence of multi-source generic ciprofloxacin hydrochloride tablets around Maiduguri metropolitan area. Nig J Pharm Sci 2009; 8: 102-106.
Osonwa UE, Agboke AA, Amadi RC, Okorie O and Opurum CC. Bioequivalence studies on some selected brands of ciprofloxacin hydrochloride tablets in the Nigerian market with ciproflox® as innovator brand. J Appl Pharmaceut Sci 2011; 1: 80-84.
Joda AE, Tayo F and Aina BA. Quality Assessment of Ciprofloxacin Tablets Obtained From Community Pharmacies In Lagos, Nigeria. Ife J Sci 2018; 20: 155-168.
NAFDAC [homepage on the internet]. List of registered Imported Drugs. National Agency for Food, Drug, Administration and Control, Lagos. [Updated] Available from: https://www.nafdac.gov.ng/wp-content/uploads/Files/Resources/Directorate_Resources/R_and_R/List-of-Registered-Imported-Drugs.pdf. Last accessed 07/07/2020.
British Pharmacopoeia, Vol. II and IV. Her Majesty’s Stationery Office, London. 2005.
United States Pharmacopoeia and National Formulary, United States Pharmacopoeia XXIII: Rockville U.S.P Convention Inc. 2007.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 16th Information supplement. Clinical and laboratory Standards Institute. Wayne. PA. 2007.
Staniforth JN and Aulton ME. Aulton’s Pharmaceutics The design and manufacture of medicines. In: Aulton ME Ed. Powder flow. 3rd Ed. New York. Churchill Livingstone 2007.
Osadebe PO and Akabuogu IC. Assessment of quality control parameters and interchangeability of multisourced metformin HCl tablets marketed in Nigeria. Boll. Chim Farma 2004; 143: 170-173.
Levi G. Comparison of dissolution and absorption rates of different commercial aspirin tablets. J Pharm Sci 1961; 50: 388-392.
Rawlins EA Eds, Bentley’s textbook of pharmaceutics. Eight Edition. ELBS and Baillière Tindall Book published by Cassell Ltd, London. 1977; 657
