JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Evaluation of Sustained-release Dosage Form with Novel Metformin Salts
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Evaluation of Sustained-release Dosage Form with Novel Metformin Salts
Kim, Dong-Wook;
  PDF(new window)
 Abstract
In this study, metformin hydrochloride for first choice of type 2 diabetes patient is administered relatively high dose, 1000 to 2000 mg orally once a day, and had very high water solubility, so it make difficult to swallow tablet to requires high amount of sustained release agent. To overcome these challenges, we used novel metformin salts had relatively low water solubility to minimize sustaining excipient for small size of dosage form. six novel metformin salts were synthesized by making metformin free form under reaction with NaOH and adding acid salts. we confirmed metformin stearate had the lowest water solubility and showed half drug release in dissolution study at 12hour. In conclusion, novel metformin salts had low water solubility can be used to reduce the size of sustained metformin tablet for improving patient compliance.
 Keywords
Metformin;Salt;Solubility;Sustained release;
 Language
Korean
 Cited by
1.
Improving the Stability of Gel Mass of Vegetable Soft Capsule, Journal of the Korea Academia-Industrial cooperation Society, 2016, 17, 5, 397  crossref(new windwow)
 References
1.
M. Rendell, Diabetes "New drug options and old choices", Consultant, Vol. 53, pp. 217-227, April, 2013.

2.
M. Ashiya, E. Richard, T. Smith, "Non-insulin therapies for type 2 diabetes", Nature Reviews Drug Discovery, Vol. 6, pp. 777-778, 2007. DOI: http://dx.doi.org/10.1038/nrd2420 crossref(new window)

3.
S. M. Setter, J. L. Iltz, J. Thams, R. K. Campbell, "Metformin hydrochloride in the treatment of type 2 diabetes mellitus: A clinical review with a focus on dual therapy", Clinical Therapeutics, Vol. 25(12), pp. 991-3026, 2003. DOI: http://dx.doi.org/10.1016/S0149-2918(03)90089-0

4.
G. G. Graham, J. Punt, M. Arora, R. O. Day, P. M. Doogue, J. Duong, J. T. Furlong, J. R. Greenfield, L. C. Greenup, C. M. Kirkpatrick, J. E. Ray, P. Timmins, M. K. Williams, "Clinical Pharmacokinetics of Metformin", Clinical Pharmacokinetics, Vol. 50(2), pp. 81-98, 2011. DOI: http://dx.doi.org/10.2165/11534750-000000000-00000 crossref(new window)

5.
P. H. Marathe, Y. Wen, J. Norton, D.S. Greene, R.H. Barbhaiya, I.R. Wilding, "Effect of altered gastric emptying and gastrointestinal motility on metformin absorption", Clinical Pharmacology, Vol. 50, pp. 325-332, 2000. DOI: http://dx.doi.org/10.1046/j.1365-2125.2000.00264.x

6.
D. Stepensky, M. Friedman, W. Srour, I. Raz, A. Hoffman, "Preclinical evaluation of pharmacokinetic pharmacodynamic rationale for oral CR metformin formulation", Journal of Controlled Release, Vol. 71, pp. 107-115, 2001. DOI: http://dx.doi.org/10.1016/S0168-3659(00)00374-6 crossref(new window)

7.
U. K. Kotreka, M. C. Adeyeye, "Gastroretentive floating drug delivery system : a critical review", Critical Reviews in Therapeutic Drug Carrier Systems, Vol. 28(1), pp. 47-99, 2011. DOI: http://dx.doi.org/10.1615/CritRevTherDrugCarrier Syst. v28.i1.20 crossref(new window)

8.
S. Arora, J. Ali, A. Ahuja, R. K. Khar, S. Baboota, "Floating Drug Delivery Systems: A Review", AAPS PharmSciTech., Vol. 6(3), pp. 372-390, 2005. DOI: http://dx.doi.org/10.1208/pt060347 crossref(new window)

9.
M. Rajab, M. Jouma, R. H. Neubert, M. Dittgen, "Influence of water-soluble polymers on the in vitro performance of floating mucoadhesive tablets containing metformin", Drug Development and Industrial Pharmacy, Vol. 40(7) pp. 879-85, 2014. DOI: http://dx.doi.org/10.3109/03639045.2013.789052

10.
M. Rajab, M. Jouma, R. H. Neubert, M. Dittgen, "Optimization of a metformin effervescent floating tablet containing hydroxypropylmethylcellulose and stearic acid", Pharmazie, Vol. 65(2), pp. 97-101, 2010.

11.
S. M. Berge, L. D. Bighley, D. C. Monkhouse, "Pharmaceutical salts", Journal of Pharmaceutical Science, Vol. 66(1), pp. 1-19, 1977. DOI: http://dx.doi.org/10.1002/jps.2600660104 crossref(new window)

12.
P. H. Stahl, C. G. Wermuth, "Handbook of Pharmaceutical Salts: Properties, Selection and Use", Weinheim/Zurich:Wiley-VCH/VHCA, 2002.

13.
J. B. Nanubolu, B. Sridhar, K. Ravikumar,, K. D. Sawant, T. A. Naik, L. N. Patkar, S. Cherukuvadac, B. Sreedhard, "Polymorphism in metformin embonate salt - recurrence of dimeric and tetrameric guanidinium? carboxylate synthons" Crystal Engineering Community, Vol. 15, pp. 4448-4464, 2013. DOI: http://dx.doi.org/10.1039/c3ce26986h crossref(new window)

14.
P. Timmins, W.J. Winter, S. K. Srivastava, A.E. Bretnall, C. Wei, G.L. Powers, "Salts of metformin and methods", US Patent 6,031,004, 2000.

15.
R.C. Rowe, P. J. Sheskey, S.C. Owen, "Handbook of Pharmaceutical Excipients, 5th ed." Pharmaceutical Press, 2006.

16.
L. C. Block, L. O. Schmeling, A. G. Couto, M. A. S. Silva, M. P. Tagliari, T. M. B. Bresolin, S. C. Mourao, "Effect of binders on 500mg metformin hydrochloride tablets produced by wet granulation", Journal of Basic and Applied Pharmaceutical Sciences, Vol. 30(2), pp. 145-152, 2009.

17.
P. Timmins, A. B. Dennis, K. A. Vyas, "Biphasic controlled release delivery system for high solubility pharmaceutical and method", US Patent 6,475,521, 2002.

18.
J. W. Kamlesh, B. K. Rajendra, J. U. Milind, "Study on sustained-release metformin hydrochloride from matrix tablet: Influence of hydrophilic polymers and in vitro evaluation", International Journal Pharmaceutical Investigation, Vol. 1(3) pp. 157-163, 2011. DOI: http://dx.doi.org/10.4103/2230-973X.85966 crossref(new window)

19.
H. G. Brittain "Analytical Profiles of Drug Substances and Excipients" Vol. 25, pp. 243-293, 1998. DOI: http://dx.doi.org/10.1016/S0099-5428(08)60757-1

20.
A. J. Wagstaff, D. P. Figgitt "Extended-release metformin hydrochloride. Single-composition osmotic tablet formulation" Treat Endocrinol. Vol. 3(5) pp. 327-32, 2004. DOI: http://dx.doi.org/10.2165/00024677-200403050-00008 crossref(new window)