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. 2007 Aug 10;8(3):E110–E117. doi: 10.1208/pt0803065

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

Hamdy Abdelkader 1,✉, Ossama Y Abdallah 2, Hesham S Salem 3
PMCID: PMC2750561  PMID: 17915815

Abstract

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1∶3 (wt/wt) drug: PVP, 25% (wt/wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at ∼129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 60 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

Keywords: Nimesulide, Polyvinylpyrrolidone, Tromethamine, Analgesic effect, Coprecipitation

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References

  • 1.Martindale . In: The Complete Drug Reference. 34th ed. Sweetman SC, editor. New York, NY: Pharmaceutical Press; 2005. pp. 1758–1789. [Google Scholar]
  • 2.Roseman TJ, Yalkowsky SH. Physicochemical properties of prostaglandin F2alpha (tromethamine salt): solubility behavior, surface properties, and ionization constants. J Pharm Sci. 1973;62:1680–1685. doi: 10.1002/jps.2600621021. [DOI] [PubMed] [Google Scholar]
  • 3.Gu L, Strickley RG. Preformulation salt selection. Physical property comparisons of the tris(hydroxymethyl)aminomethane (THAM) salts of four analgesic/antiinflammatory agents with the sodium salts and the free acids. Pharm Res. 1987;4:255–257. doi: 10.1023/A:1016420514689. [DOI] [PubMed] [Google Scholar]
  • 4.Borsa F, Leroy A, Fillastre JP, Godin M, Moulin B. Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults. Antimicrob Agents Chemother. 1988;32:932–941. doi: 10.1128/aac.32.6.938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Gwak HS, Chun IK. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int J Pharm. 2002;236:57–64. doi: 10.1016/S0378-5173(02)00009-1. [DOI] [PubMed] [Google Scholar]
  • 6.Loftsson T, Fridriksdottir H. Stabilizing effect of tris(hydroxymethyl) aminomethane on N-nitrosoureas in aqueous solutions. J Pharm Sci. 1992;81:197–198. doi: 10.1002/jps.2600810219. [DOI] [PubMed] [Google Scholar]
  • 7.Rabasco AM, Caraballo I, Fernandez AM. Formulation factors affecting thimerosal stability. Drug Dev Ind Pharm. 1993;19:1673–1691. doi: 10.3109/03639049309050160. [DOI] [Google Scholar]
  • 8.McGloughlin RM, Corrigan OI. Dissolution characteristics of benzoic acid-TRIS mixtures. Int J Pharm. 1992;82:135–143. doi: 10.1016/0378-5173(92)90082-D. [DOI] [Google Scholar]
  • 9.El Sayed GM. Role of tromethamine as a dissolution and bioavailability enhancer of oral glibenclamide. STP Pharma Sci. 1998;8:169–173. [Google Scholar]
  • 10.Gabr KE, Borg TM. Characterization of hydrochorothiazide-trometamol mixtures: formulation of fast release and soluble tablets. Pharm Ind. 1999;61:281–285. [Google Scholar]
  • 11.Magda AE. Physicochemical characterisation of coprecipitates of Furesemide with Tromethamine. Alex J Pharm Sci. 2005;19:1–8. [Google Scholar]
  • 12.Singla AK, Chawla M, Singh A. Nimesulide: some pharmaceutical and pharmacological aspects-an update. J Pharm Pharmacol. 2000;52:467–475. doi: 10.1211/0022357001774255. [DOI] [PubMed] [Google Scholar]
  • 13.Meriani F, Coceani N, Sirotti C, Voinovich V, Grassi M. Characterization of a quaternary liquid system improving the bioavailability of poorly water soluble drugs. J Colloid Interface Sci. 2003;263:590–596. doi: 10.1016/S0021-9797(03)00321-7. [DOI] [PubMed] [Google Scholar]
  • 14.Piel G, Pirotte B, Delneuveille I. Study of the influence of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide: isolation and characterization of nimesulide-L-lysine-cyclodextrin complexes. J Pharm Sci. 1997;86:475–480. doi: 10.1021/js960298k. [DOI] [PubMed] [Google Scholar]
  • 15.Gohel MC, Patel LD. Processing of nimesulide-PEG 400-PG-PVP solid dispersions: preparation, characterization, and in vitro dissolution. Drug Dev Ind Pharm. 2003;29:299–310. doi: 10.1081/DDC-120018203. [DOI] [PubMed] [Google Scholar]
  • 16.Hamdy AM. Improvement and evaluation of some formulations for skeletal muscle drugs [master's thesis] Minia, Egypt: Pharmaceutics Department, Minia University; 2006. [Google Scholar]
  • 17.Singh A, Singh P, Kapoor VK. Analytical Profiles of Drug Substances and Excipients. New York, NY: Academic Press; 2001. pp. 198–249. [Google Scholar]
  • 18.Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27:48–49. doi: 10.1111/j.2042-7158.1975.tb09378.x. [DOI] [PubMed] [Google Scholar]
  • 19.Tanaka R, Shimotori T, Makino S. Pharmacological studies of the new anti-inflammatory agent 3-formyl amino-7-methylsulfonyl amino-6-phenoxy 4 H-1benzopyran-4-one. Arzneim Forsch. 1992;42:935–944. [PubMed] [Google Scholar]
  • 20.Inoue K, Fujisawa H, Motonaga A, et al. Anti-inflammatory effects of etodolac:comparison with other non-steroidal anti-inflammatory drugs. Biol Pharm Bull. 1994;17:1577–1583. doi: 10.1248/bpb.17.1577. [DOI] [PubMed] [Google Scholar]
  • 21.Adhage NA, Vavia PR. β-cyclodextrin inclusion complexation by milling. Pharm Pharmacol Commun. 2000;6:13–17. [Google Scholar]
  • 22.Zerrouk N, Mennini N, Francesca M, Chemtob C, Mura P. Comparison of the effect of chitosan and polyvinylpyrrolidone on dissolution properties and analgesic effect of naproxen. Eur J Pharm Biopharm. 2004;57:93–99. doi: 10.1016/S0939-6411(03)00112-7. [DOI] [PubMed] [Google Scholar]
  • 23.Bettinetti GP, Mura P, Giordano F, Setti M. Thermal behaviour and physicochemical properties of naproxen in mixtures with polyvinylpyrrolidone. Thermochim Acta. 1992;199:165–171. doi: 10.1016/0040-6031(92)80260-4. [DOI] [Google Scholar]
  • 24.Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci. 1971;60:1281–1302. doi: 10.1002/jps.2600600902. [DOI] [PubMed] [Google Scholar]
  • 25.Craig DQ. Polyethylene glycols and drug release. Drug Dev Ind Pharm. 1990;16:2501–2526. doi: 10.3109/03639049009058544. [DOI] [Google Scholar]
  • 26.The United States Pharmacopoeia 28 and NF23. Rockville, MD: United States Pharmacopoeial Convention; 2005.

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