Abstract
Background: To determine the pharmaceutical equivalence and stability of eighteen randomly selected brands of metronidazole suspensions.
Methods: The tests conducted include ease of re-dispersibility, sedimentation volume, particle size measurements, viscosity and assay of drug content.
Results: The results showed that 16 (88.9%) out of 18 brands including the innovator (SR) were re-dispersed between 30seconds to one minute, while 2 (11.1%) took more than two minutes. The sedimentation volume for 15 (83.3%) of the brands was less than 0.50 while the innovator brand had a significantly higher (p<0.001) value (0.91). The particle size of the brands ranged between 1.942 and 5.921µm and the sedimentation rate was between 20-50mL/day. The viscosity of the brands were significantly different (p<0.05) with SA, SB, SC, SD, SE and SF having 250-400cp, brands SG, SH, SI, SM, SP and SQ had 10-50cp while the remaining six brands had 100-190cp. Four brands including the innovator (SK, SP, SQ and SR) met Pharmacopoeal requirement for metronidazole suspension on drug content. Moreover, colour change, reduced viscosity and significant increase (p<0.05) in particle sizes were observed for samples stored at 420C for seven weeks while those stored at 40C and 250C maintained stability.
Conclusion: Four out of eighteen brands of metronidazole suspensions evaluated in this study were found to be pharmaceutically equivalent. The stability studies showed that there is the need to adhere strictly to storage of metronidazole suspensions in a cool place.
Keywords: Metronidazole suspensions, pharmaceutical properties, drug content, stability pharmaceutical equivalence.
Résumé
Introduction: Pour déterminer l’équivalence et stabilité pharmaceutique de dix huit tisons de suspensions metronidazole sélectionnés au hasard.
Méthode: Les tests menés contenaient aise de ré-dissipation, volume de sédimentation, mesures sur la taille de la particule, viscosité et vérification du contenue de la drogue.
Résultats : Les résultats montraient que 16 (88,9%) parmi 18 tisons y compris l’innovateur (SR) étaient rédissipés entre 30 secondes et une minute, tandis que 2 (11,1%) pris plus que deux minutes. Le volume de sédimentation pour 15 (83,3%) des tisons était moins que 0,50 tandis que le tison innovateur avait une grande valeur (0,91) significative (p<0,001). La taille de particule des tisons rangeait entre 1,942 et 5,921 µm et le taux de sédimentation était entre 20-50 ml/jour. La viscosité des tisons étaient significativement différente (p<0,05) avec SA, SB, SC, SD, SE et SF ayant 250-400cp, les tisons SG, SH, SI, SM, SP et SQ avaient 10-50cp, tandis que les six restants avaient 100-190cp. Quatre tisons y compris l’innovateur (SK, SP, SQ et SR) étaient convenables avec la qualité Pharmacopée requise pour suspension metronidazole sur contenu de drogue. De plus, changement de couleur, viscosité réduite et accroissement signifiant (p<0,05) en tailles de particule étaient observés pour les échantillons pourvus à 420C pour sept semaine tandis que ceux pourvus à 40C et 250Cmaintenaient stabilité.
Conclusion: Quatre des dix huit tisons de suspensions metronidazole évalués dans cette étude étaient trouvés à être de manière pharmaceutique équivalent. Les études de stabilité montraient qu’il y a le besoin d’adhérer strictement à l’approvisionnement des suspensions metronidazole dans un lieu froid.
Mots clés: Suspensions de metronidazole, propriétés pharmaceutique, contenu de drogue, équivalence de stabilité pharmaceutique.
Correspondence: Prof. O.A. Odeku, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria. E-mail: o.odeku@mail.ui.edu.ng; pejuodeku@yahoo.com
References
Zietsman S, Kilian G, Worthington M and Stubbs C. Formulation development and stability of aqueous metronidazole suspensions containing various suspending agents. Drug Dev. and Ind. Pharm. 2007; 33 (2): 191-197
Patel RM. Parenteral suspension: an overview. International Journal of Current Pharmaceutical Research 2010; 2 (3) 4-13
Saeedi M, Dallalpoor-Mohammadi N and Farid D. Prevention of crystal growth in acetaminophen suspensions by the use of polyvinyl pyrrolidone and bovine serum albumin. DARU. 2003;11 (3): 1-9
Attwood D. Disperse systems. In M.E Aulton (ed.). Pharmaceutics-The Science of Dosage Form Design, 2nd Edition, Edinburgh, Churchill Livingstone; 2002; 77-82, 91-92.
Ansel, HC, Allen LV and Popovich NG. (eds). Pharmaceutical Dosage Forms and Drug Delivery Systems. 7th Edition, , Philadelphia, Lippincott Williams and Wilkins; 1999; 64-67, 347-348.
Freeman CD, Klutman NE and Lamp KC. Metronidazole: A therapeutic review and update. Drugs. 1997; 54 (5):679-708.
Idkaidek NM and Najib NM. Enhancement of oral absorption of metronidazole suspension in humans. Eur. J. Pharm. Biopharm. 2000; 50: 213-216
Alestig K, Freij L and Arnold E. Absorption and excretion of metronidazole after administration of metronidazole benzoate mixture. Scand J Infect Dis. 1980; 12, 149-152.
Adegbolagun OA, Olalade OA and Osumah SE. Comparative evaluation of the biopharma- ceutical and chemical equivalence of some commercially available brands of ciprofloxacin hydrochloride tablets. Trop. J. pharm. Res. 2007; 6 (3): 737-745.
Adegbolagun OA, Jegede OJ and Olaniyi AA. Chemical equivalence studies on four brands of Metronidazole tablets. Nig. J. pharm. Res 2002; 9, 71-74
Okeke I and Lamikanra A Quality and bioavailability of Tetracycline Capsule in Nigerian semi-urban community. Intern. J. Antimicrob. Agents 1995; 5: 245-268
Iwuagwu MA and Onyeonwu N. In-vitro Assesment of Ampicillin Capsules Marketed in Nigeria. Int. J. Pharm. Pract. 1992. 1: 167-171
Taylor RB, Shakoor O, Behrens RH, et al. The quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria. The Lancet 2001; 357 (9272): 1933–1936
Oladimeji OA and Ifudu, ND. A comparative evaluation of local plantain mucilage as pharmaceutical suspending agent. Nig. J. Pharm. 1998; 19 (6). 206-208
Femi-Oyewo MN, Adedokun MO and Olusoga TO. Evaluation of the suspending properties of Albizia zygia gum on sulphadimidine suspension. Tropic. Journal of Pharm. Research 2004; 3 (1); 279-284
Abdelaleem EA and Abdelwahab NS. Simultaneous determination of some antiprotozoal drugs in different combined dosage forms by mean centering of ratio spectra and multivariate calibration with model updating methods. Chemistry Central Journal 2012, 6:27-31.
Higuchi WI, Swarbrick JS and Simonelli AP. Particle phenomenon and coarse dispersions. In: Remington’s Pharmaceutical Science, 16th ed. Easton PA: Mack publishing Co. 1980; 294-297
Zatz, JL. Physical stability of suspensions. J. Soc. Cosmet. Chem.1985; 36: 393-411
Swarbrick J, Rubino JT and Rubino OP. Coarse Dispersions. In A.R Gennaro (ed.), Remington: The Science and Practice of Pharmacy, 20th Edition, Pennsylvania: Lippincott Williams & Wilkins; 2000; 317-322.
Alok KK, Onkar NS and Michael GW. Pharmaceutical Suspensions. In: Formulation development to manufacturing, LLC, 233 spring street, NewYork, USA. Springer Science and Business Media; 2010; 52-53.
Florence AT and Attwood D. Physicochemical Principles of Pharmacy, 2nd Edition, London: The Macmillan Press Ltd; 1988; 260, 262, 281, 299, 300, 311.
Marriot C. Rheology: In Pharmaceutics. The Science of Dosage Form Design.2nd edition Aulton M.E (eds). Edinburgh; Churchill Livingstone 2002; 40-58.
Tempio SJ and Zatz JL. Flocculation effect of Xanthan Gum in pharmaceutical suspensions. J. Pharm. . Sci. 1980; 69 (10): 1209-1214
Ogaji IJ and Hoag SW. Effect of Grewia Gum as a Suspending Agent on Ibuprofen Pediatric Formulation. AAPS PharmSciTech, 2011; 12 (2): 507-513
The International Pharmacopeia (IP). World Health Organization Pharmacopoeia Library Dosage Form specific monographs. 2013; Vol. I. 4th Edition, 3rd supplement.
Kahaliw W and Ashenef A. Comparative quality evaluation of some metronidazole tablets and metronidazole benzoate oral suspensions available in retail outlets of Addis Ababa, Ethiopia. Int. J. Pharm. Scs.Res. 2013; 4(4) 1384-1391
Liberman A, Martin A and Rieger M. Disperse systems. In: Gilbert’s Pharmaceutical Dosage Forms. Vol.2. Marcel Dekker 1996; 285-287
Bello NJ (ed.). Climate Change: Implications for Food Production and Security in Nigeria. In climate Change Impacts and Adaptation: Developmental Issues. Nigeria: The Nigerian Meteorological Society 2010; 4-10.
Nigerian Meteorological Agency. Nigeria Climate Review Bulletin 2010; p 1-33. Accessed October 10, 2013 @ http://www.nimetng.org/uploads/publication/2010climate
Ashford M. Bioavailability-physicochemical and dosage form factors. In ME Aulton (ed.), Pharmaceutics,-The Science of Dosage Form Design, 2nd Edition; Edinburgh, Churchill Livingstone; 2002; 244- 245.