Abstract
The purpose of this research was to formulate tasteless complexes of ciprofloxacin with Indion 234 and to evaluate molecular properties of drug complexes. The effect of batch and column process, complexation time, temperature, and pH on ciprofloxacin loading on Indion 234 is reported. Drug resin complexes (DRC) were characterized by infrared spectroscopy, thermal analysis, and x-ray diffraction pattern. Ciprofloxacin release from DRC is obtained at salivary and gastric pH and in the presence of electrolytes. The efficient drug loading was evident in batch process using activated Indion 234 with a drug-resin ratio of 1∶1.3. Drug complexation enhanced with pH from 1.2 to 6, while temperature did not affect the complexation process. Infrared spectroscopy revealed complexation of—NH (drug) with Indion 234. DRC are amorphous in nature. Drug release from DRC in salivary pH was insufficient to impart bitter taste. Volunteers rated the complex as tasteless and agreeable. Complete drug release was observed at gastric pH in 2 hours. The drug release was accelerated in the presence of electrolytes. Indion 234 is inexpensive, and the simple technique is effective for bitterness masking of ciprofloxacin.
Keywords: ciprofloxacin, Indion 234, tasteless complex, characterization, electrolyte, release
Full Text
The Full Text of this article is available as a PDF (226.9 KB).
References
- 1.Glen M. Taste masking in oral pharmaceuticals. Pharm Technol. 1994;18(4):84–98. [Google Scholar]
- 2.Aoi M, Murata A, inventors. Control of bitter taste of pharmaceuticals and food. Japanese patent 04346937. February 12, 1992.
- 3.Blase CM, Shah M, inventors. Taste masked pharmaceutical suspensions containing xanthum gum and microcrystalline cellulose. European patent 0556057. August 18, 1993.
- 4.Gowan WG, Bruce RD, inventors. Aliphatic or fatty acid as a solventless carriers for pharmaceuticals. US patent 5 405 617. April 11, 1995.
- 5.Kasturagi Y, Kurihari K. Specific inhibitors for bitter taste. Nature. 1993;6443:213–214. doi: 10.1038/365213b0. [DOI] [PubMed] [Google Scholar]
- 6.Motola S, Agisim G, inventors. Palatable ibuprofen solutions. US patent 5 024 997. June 18, 1991.
- 7.Robert R, Brown J. Solubility limiting methods. German patent office. 39214. March 25, 1990.
- 8.Deasy PB. Microencapsulation and related drug processes. In: Swarbrick J, Boylan JC, editors. Encyclopedia of Pharmaceutical Technology. New York, NY: Marcel Dekker; 1984. pp. 241–243. [Google Scholar]
- 9.Patricia K, Edward R, Joel S, Imtiaz C, inventors. Sustained release oral suspensions. US patent 4 999 189. March 12, 1991.
- 10.Betty W, Michael P, Dokuzovic V, Lam V. Antitussive drugs delivered by ion exchange resins. US patent 6 001 392. December 14, 1999.
- 11.Borodkin P, Sundberg PD. Polycarboxylic acid ion-exchange resin adsorbates for taste coverage in chewable tablets. J Pharm Sci. 1971;60:1523–1527. doi: 10.1002/jps.2600601018. [DOI] [PubMed] [Google Scholar]
- 12.Maria CB, Silvia S, Franc F, Evy S, Angelina PR, Carla C. Factorial analysis of the influence of dissolution medium on drug release from carrageenan-diltiazem complexes. AAPS Pharm Sci Tech. 2000;1:E15–E15. doi: 10.1208/pt010215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Carola A, Maria CB, Maria R, Silvia S, Franaca F, Carla C. Influence of complex solubility on formulations based on lambda carrageenan and basic drugs. AAPS Pharm Sci Tech. 2002;3:E27–E27. doi: 10.1208/pt030327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Akkaramonkolporn P, Katsuhide T. Molecular properties of propranolol hydrochloride prepared as drug-resin complexes. Drug Dev Ind Pharm. 2001;27:359–364. doi: 10.1081/DDC-100103736. [DOI] [PubMed] [Google Scholar]
- 15.Raghunanthan Y, Amsel L, Hinsvark ON, Bryant WJ. Sustained-release drug delivery system. I: Coated ion-exchange resin system for phenylpropanolamine and other drugs. J Pharm Sci. 1981;70:379–383. doi: 10.1002/jps.2600700409. [DOI] [PubMed] [Google Scholar]
- 16.Borodkin S. Ion exchange resin delivery systems. In: Tarcha PJ, editor. Polymers for Controlled Drug Delivery. Boca Raton, FL: CRC Press; 1991. pp. 215–230. [Google Scholar]
- 17.Borodkin S, Yunker MH. Interaction of amine drugs with a polycarboxylic acid ion-exchange resin. J Pharm Sci. 1970;59:481–486. doi: 10.1002/jps.2600590409. [DOI] [PubMed] [Google Scholar]
- 18.Vaviya S, Bajaj A. Oral controlled release bromhexine ion exchange resinate suspension formulation. Ind Drugs. 2000;37:185–189. [Google Scholar]
- 19.Santos L, Ghaly ES. Design and development of suspension containing drug resin complex. AAPS Pharm Sci. 2003;5(S1):T3257–T3257. [Google Scholar]
- 20.Borodkin SS. Ion exchange resins and sustained release. In: Swarbrick J, Boylan JC, editors. Encyclopedia of Pharmaceutical Technology. New York, NY: Marcel Dekker; 1993. pp. 241–243. [Google Scholar]
- 21.Agarwal R, Mittal R. Studies on ion exchange resin complex of chloroquine phosphate. Drug Dev Ind Pharm. 2001;27:359–364. doi: 10.1081/DDC-100103736. [DOI] [PubMed] [Google Scholar]
- 22.Glasstone S, Lewis D. Elements of Physical Chemistry. London, UK: Macmillan and Company, Ltd; 1960. [Google Scholar]
- 23.Frank D, Koebel B. Some like it hot, some like it cold. Water Quality. 2000;54:54–57. [Google Scholar]
- 24.Plazier VJA. Investigation of the bioavailability of codeine from a cation ion-exchange sulfonic acid. I. Effect of parameters. Int J Pharm. 1992;85:45–50. doi: 10.1016/0378-5173(92)90132-L. [DOI] [Google Scholar]
- 25.Silverstein RM, Bassler GC, Morrill TC. Infrared spectroscopy. In: Dennis S, editor. Spectroscopic Identification of Organic Compounds. Singapore: John Wiley; 1991. pp. 91–133. [Google Scholar]
- 26.Conaghey OM, Coris J, Corrigan OI. The release of nicotine from a hydrogel containing ion exchange resins. Int J Pharm. 1998;170:215–224. doi: 10.1016/S0378-5173(98)00144-6. [DOI] [Google Scholar]
- 27.Jasari T, Vuorio M. Ion exchange fibers and drugs: an equilibrium study. J Control Release. 2001;70:219–229. doi: 10.1016/S0168-3659(00)00359-X. [DOI] [PubMed] [Google Scholar]
- 28.Herrera T, Matejka Z, Eliasek J. Cation exchange kinetics on carboxylic acid resins in a multicomponent system H−Me+−Me2+ Desalination. 1983;48:161–169. doi: 10.1016/0011-9164(83)80014-9. [DOI] [Google Scholar]
- 29.Liu Z, Cheung R, Wu Yu X, James R. A study of doxorubicin loading onto and release from sulfopropyl dextran ion-exchange microspheres. J Control Release. 2001;77:213–224. doi: 10.1016/S0168-3659(01)00473-4. [DOI] [PubMed] [Google Scholar]