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. 2015 Feb 19;1(2):72–79. doi: 10.1208/pt010215

Factorial analysis of the influence of dissolution medium on drug release from carrageenan-diltiazem complexes

Maria Cristina Bonferoni 1, Silvia Rossi 1, Franca Ferrari 1, Evy Stavik 1, Angelina Pena-Romero 1, Carla Caramella 1,
PMCID: PMC2784826  PMID: 14727848

1bstract

This research studied the influence of buffer composition, pH, and ionic strength on the release of diltiazem hydrochloride from a complex of the drug with lambda carrageenan. Two viscosity grades of carrageenan were also compared. A factorial analysis was used to evaluate the influence of individual variables and their interactions. Both the complex solubility, measured as the drug concentration in equilibrium with the solid complex, and the drug release rate from constant surface area were considered. The increase of ionic strength significantly increased complex solubility in all the buffer systems. A significant effect of polymer grade on complex solubility was evidenced only in phosphate buffer with a pH of 6.8, indicating lower solubility of the complex when higher polymer molecular weight was involved. In most cases, drug release rate decreased when high polymer grade was involved in the complex. Ionic strength did not always have a significant effect on drug release rate and was quantitatively less important than for solubility lonic strength especially affected the drug release profiles. At higher ionic strength drug release was no longer constant, but decreased with time, probably because of lower polymer solubility.

Keywords: lambda carrageenan, 4rug-polymer complex, 4iltiazem HCl, 4issolution medium pH and ionic strength, Factorial analysis

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References

  • 1.Graham HD, Baker YM, Njoku-obi AN. Complex formation between hydrocolloids and tranquilizers and hypotensive agents. J Pharm Sci. 1963;52:192–198. doi: 10.1002/jps.2600520224. [DOI] [PubMed] [Google Scholar]
  • 2.Graham HD, Baker YM. Interaction of antihistamines with hydrocolloids. J. Pharm. Sci. 1963;52:964–967. doi: 10.1002/jps.2600521011. [DOI] [PubMed] [Google Scholar]
  • 3.Takahashi Y, Nambu N, Nagai T. Interaction of several nonsteroidal antiinflammatory drugs with pectin in aqueous solution and in solid state. Chem Pharm. Bull. 1978;26:3836–3842. doi: 10.1248/cpb.26.3836. [DOI] [Google Scholar]
  • 4.Bonferoni MC, Rossi S, Tamayo M, Pedraz JL, Dominguez Gil A, Caramella C. On the employment of λ carrageenan in a matrix system. I. Sensitivity to dissolution medium and comparison with Na carboxymethylcellulose and xanthan gum. J. Controlled Rel. 1993;26:119–127. doi: 10.1016/0168-3659(93)90111-H. [DOI] [Google Scholar]
  • 5.Bonferoni MC, Rossi S, Tamayo M, Pedraz JL, Dominguez Gil A, Caramella C. On the employment of λ carrageenan in a matrix system. II. λ carrageenan and hydroxypropylmethylcellulose mixtures. J. Controlled Rel. 1994;30:175–182. doi: 10.1016/0168-3659(94)90264-X. [DOI] [Google Scholar]
  • 6.Bonferoni MC, Rossi S, Ferrari F, Bertoni M, Bolhuis GK, Carmella C. On the employment of λ carrageenan in a matrix system. III. Optimization of a λ carrageenan-HPMC hydrophilic matrix. J. Controlled Rel. 1998;51:231–239. doi: 10.1016/S0168-3659(97)00175-2. [DOI] [PubMed] [Google Scholar]
  • 7.Bonferoni MC, Rossi S, Ferrari F, Bettinetti GP, Caramella C. Characterization of a diltiazem-lambda carrageenan complex. Int. J. Pharm. 2000;200:207–216. doi: 10.1016/S0378-5173(00)00389-6. [DOI] [PubMed] [Google Scholar]
  • 8.Bonferoni, MC, Rossi S, Ferrari F., Caramella, C. Development of a once-a-day tablet formulation based on a diltiazem carrageenan interaction product. Paper presented at 2nd World Meeting APGI/APV; May 25–28. 1998, Paris. France.
  • 9.Lindhal A, Ungell AL, Knutson L, Lennernas H. Characterization of fluids from the stomach and proximal jejunum in men and women. Pharm. Res. 1997;14:497–502. doi: 10.1023/A:1012107801889. [DOI] [PubMed] [Google Scholar]
  • 10.Plaizier-Vereammen JA, De Nève RE. Interaction of Povidone with aromatic compounds I: evaluation of complex formation by factorial analysis. J. Pharm. Sci. 1980;69:1403–1408. doi: 10.1002/jps.2600691213. [DOI] [PubMed] [Google Scholar]
  • 11.Plaizier-Vercammen JA, De Nève RE. Interaction of Povidone with aromatic compounds II: evaluation of ionic strength, buffer concentration, temperature and pH by factorial analysis. J. Pharm. Sci. 1981;70:1251–1256. doi: 10.1002/jps.2600701118. [DOI] [PubMed] [Google Scholar]
  • 12.Peppas NA. Analysis of Fiekian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–111. [PubMed] [Google Scholar]

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