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2010 | 5 | 1 | 83-90
Tytuł artykułu

Impact of pharmaceutical dosage form on stability and dissolution of roxithromycin

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The behavior of dispersible tablets containing enteric-coated pellets and oral suspension, both containing roxithromycin, was investigated using dissolution tests in different media. The dissolution test was performed under different pH conditions. For both dosage forms investigated, the test was conducted at pH 1.2, 4.5, and 6.8. Additionally, for dispersible tablets, the test involving increasing pH was performed at pH 1.2 (acid stage) and afterwards at pH 6.8 (buffer stage). The extent of dissolution was measured using high-performance liquid chromatography (HPLC). In all cases tested, roxithromycin underwent rapid degradation at pH 1.2. Dispersible tablets displayed the features of modified release preparations with a non-complete dissolution during the test times in all media. Conversely, the oral suspension behaved as an immediate release preparation, with degradation at pH 1.2. However, the dissolution of the oral suspension at pH 4.5 and 6.8 was rapid and complete. The role of enteric-coated pellets is to mask the bitter taste of the active substance upon administration. However, the coating showed lack of resistance to media at pH 1.2. Therefore, dispersible tablets containing enteric-coated pellets are not pharmaceutically equivalent to the immediate-release oral suspension.

Opis fizyczny
  • R&D Department, Polfa Tarchomin SA, Fleminga 2, 03-176, Warszawa, Poland
  • R&D Department, Polfa Tarchomin SA, Fleminga 2, 03-176, Warszawa, Poland
  • Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland,
  • [1] Young RA, Gonzales JP, Sorkinm EM, Roxithromycin. A review of its antibacterial activity. Pharmacokinetics properties and clinical efficacy, Drugs, 1989, 37, 8–41[Crossref]
  • [2] Markham A, Faulds D, Roxithromycin: An update of its antimicrobial activity, pharmacokinetics properties and therapeutic use, Drugs, 1994, 48, 297–326[Crossref]
  • [3] Mazzei T, Mini E, Novelli A, Chemistry and mode action of macrolides, J. Antimicrob. Chemother., 1993, 31, 1–9[Crossref]
  • [4] Fournet M-P, Zini R, Deforges L, Duval J, Tillement J-P, Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionella pneumophilia, J. Pharm. Sci., 1987, 76, 153–156[Crossref]
  • [5] Kuenzi B, Segessenmann CH, Gerber AU, Postantibiotic effect roxithromycin, erythromycin and clindamycin against selected Gram-ppositive bacteria and Haemophilus influenze, J. Antimicrob. Chemother., 1987, 20, 39–46 [Crossref]
  • [6] Gasc J-C, D’Ambrieres SG, Lutz A, Chantot J-F, New ether oxime derivatives of erythromycin A. A structure-activity relationship study, J. Antibiot., 1991, 44, 313–330 [Crossref]
  • [7] Zhong D, Li X., Wang A., Xu Y., Wu S, Identification of the metabolites of roxithromycin in humans, Drug Metab. Dispos., 2000, 28, 552–559 [PubMed]
  • [8] Huang H, Yu LH, Sun, TM, In vitro antibacterial activity of roxithromycin and its major metabolites, Chin. J. Antibiot., 2002, 25, 443–446
  • [9] Sun J, Zhang T, Qiu F, Liu Y, Tang J, Huang H, He Z, Impact of pharmaceutical dosage forms on the pharmacokinetics of roxithromycin in healthy human volunteers, J. Antimicrob. Chemother., 2005, 55, 796–799[Crossref]
  • [10] Ostrowski M, Wilkowska E, Baczek T, In vivo-in vitro correlation for amoxicillin trihydrate 1000 mg dispersible tablet, Dsrug Dev. Ind. Pharm., 2009, 35, 981–985[Crossref]
  • [11] Hang S, Xing J, Hong D, pH-dependent geometric isomerisation of roxithromycin in simulated gastrointestinal fluids and in rats, J. Pharm. Sci., 2004, 93, 1300–1309[Crossref]
  • [12] Motta M, Ribeiro W, Ifa DR, Moares ME, Moraes MO, Corrado AP, De Nucci G, Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid chromatography coupled to tandem mass spectrometry, Acta Physiol. Pharmacol. Ther. Latinoam., 1999, 49, 233–241 [PubMed]
  • [13] Nakagawa Y, Itai S, Yoshida T, Nagai T, Physicochemical properties and stability in the acidic solution of a new macrolide antibiotic, clarithromycin in comparison with erythromycin, Chem. Pharm. Bull., 1992, 40, 725–728 [PubMed][Crossref]
  • [14] Morimoto S, Misawa Y, Asaka T, Kondoh H, Watanabe Y, Chemical modification of erythromycins. VI. Structure and antibacterial activity of acid degradation products of 6-O-methylerythromycins A, J. Antibiot., 1990, 43, 570–573 [Crossref]
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