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Drug Res (Stuttg) 2014; 64(3): 118-123
DOI: 10.1055/s-0033-1353186
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Drug Release Kinetic Analysis and Prediction of Release Data via Polymer Molecular Weight in Sustained Release Diltiazem Matrices

K. Adibkia
1   Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
,
S. Ghanbarzadeh
1   Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
,
G. Mohammadi
2   Faculty of Pharmacy, Pharmaceutics, Kermanshah, Islamic Republic of Iran
,
H. Z. Khiavi
1   Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
,
A. Sabzevari
3   Faculty of Pharmacy, Pharmaceutics, Tehran, Islamic Republic of Iran
,
M. Barzegar-Jalali
1   Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 15 July 2013

accepted 27 July 2013

Publication Date:
28 August 2013 (online)

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Abstract

Background:

This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.

Methods:

Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer’s molecular weight, dissolution data were fitted into two proposed equations.

Results:

All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.

Conclusion:

Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release.

Key words

diltiazem - matrix tablets - sustained-release - HPMC - tragacanth - kinetic models
 

  • References

  • 1 Rabkin SW. The calcium antagonist diltiazem has antiarrhythmic effects which are mediated in the brain through endogenous opioids. Neuropharmacology 1992; 31: 487-496
    CrossrefPubMedGoogle Scholar
  • 2 Smith DHG, Neutel JM, Weber MA. Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem. Am J Hypertens 1999; 12: 1030-1037
    CrossrefPubMedGoogle Scholar
  • 3 Takeo S, Tanonaka K, Iwai T et al. Preservation of mitochondrial function during ischemia as a possible mechanism for cardioprotection of diltiazem against ischemia/reperfusion injury. Biochem Pharmacol 2004; 67: 565-574
    CrossrefPubMedGoogle Scholar
  • 4 Junyaprasert VB, Manwiwattanakul G. Release profile comparison and stability of diltiazem/resin microcapsules in sustained release suspensions. Int J Pharm 2008; 352: 81-91
    CrossrefPubMedGoogle Scholar
  • 5 Kakish HF, Tashtoush B, Ibrahim HG et al. A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium. Eur J Pharm Biopharm 2002; 54: 75-81
    CrossrefPubMedGoogle Scholar
  • 6 Levis SR, Deasy PB. Use of coated microtubular halloysite for the sustained release of diltiazem hydrochloride and propranolol hydrochloride. Int J Pharm 2003; 253: 145-157
    CrossrefPubMedGoogle Scholar
  • 7 Mandal S, Basu SK, Sa B. Ca2+ ion cross-linked interpenetrating network matrix tablets of polyacrylamide-grafted-sodium alginate and sodium alginate for sustained release of diltiazem hydrochloride. Carbohydr Polym 2010; 82: 867-873
    CrossrefPubMedGoogle Scholar
  • 8 Toti US, Aminabhavi TM. Modified guar gum matrix tablet for controlled release of diltiazem hydrochloride. J Controlled Release 2004; 95: 567-577
    CrossrefPubMedGoogle Scholar
  • 9 Uekama K, Horikawa T, Horiuchi Y et al. In vitro and in vivo evaluation of delayed-release behavior of diltiazem from its O-carboxymethyl-O-ethyl-cyclodextrin complex. J. Controlled Release 1993; 25: 99-106
    CrossrefPubMedGoogle Scholar
  • 10 Wilding IR, Hardy JG, Maccari M et al. Scintigraphic and pharmacokinetic assessment of a multiparticulate sustained release formulation of diltiazem. Int J Pharm 1991; 76: 133-143
    CrossrefPubMedGoogle Scholar
  • 11 Ishida M, Abe K, Hashizume M et al. A novel approach to sustained pseudoephedrine release: Differentially coated mini-tablets in HPMC capsules. Int J Pharm 2008; 359: 46-52
    CrossrefPubMedGoogle Scholar
  • 12 Shah AC, Britten NJ. Novel divisible tablet designs for sustained release formulations. J Controlled Release 1990; 14: 179-185
    CrossrefPubMedGoogle Scholar
  • 13 Abdelbary GA, Tadros MI. Design and in vitro/in vivo evaluation of novel nicorandil extended release matrix tablets based on hydrophilic interpolymer complexes and a hydrophobic waxy polymer. Eur J Pharm Biopharm 2008; 69: 1019-1028
    CrossrefPubMedGoogle Scholar
  • 14 Fan J, Wang K, Liu M et al. In vitro evaluations of konjac glucomannan and xanthan gum mixture as the sustained release material of matrix tablet. Carbohydr. Polym 2008; 73: 241-247
    CrossrefPubMedGoogle Scholar
  • 15 Fukuda M, Peppas NA, McGinity JW. Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum. Int J Pharm 2006; 310: 90-100
    CrossrefPubMedGoogle Scholar
  • 16 Furlanetto S, Cirri M, Maestrelli F et al. Study of formulation variables influencing the drug release rate from matrix tablets by experimental design. Eur J Pharm Biopharm 2006; 62: 77-84
    CrossrefPubMedGoogle Scholar
  • 17 Jian H, Zhu L, Zhang W et al. Galactomannan (from Gleditsia sinensis Lam.) and xanthan gum matrix tablets for controlled delivery of theophylline: In vitro drug release and swelling behavior. Carbohydr Polym 2012; 87: 2176-2182
    CrossrefPubMedGoogle Scholar
  • 18 Anderson DMW, Bridgeman MME. The composition of the proteinaceous polysaccharides exuded by astragalus microcephalus, A. Gummifer and A. Kurdicus – The sources of turkish gum tragacanth. Phytochemistry 1985; 24: 2301-2304
    CrossrefPubMedGoogle Scholar
  • 19 Azarikia F, Abbasi S. On the stabilization mechanism of Doogh (Iranian yoghurt drink) by gum tragacanth. Food Hydrocolloids 2010; 24: 358-363
    CrossrefPubMedGoogle Scholar
  • 20 Eastwood MA, Brydon WG, Anderson DMW. The effects of dietary gum tragacanth in man. Toxicol Lett 1984; 21: 73-81
    CrossrefPubMedGoogle Scholar
  • 21 Gavlighi HA, Meyer AS, Zaidel DNA et al. Stabilization of emulsions by gum tragacanth (Astragalus spp.) correlates to the galacturonic acid content and methoxylation degree of the gum. Food Hydrocolloids 2013; 31: 5-14
    CrossrefPubMedGoogle Scholar
  • 22 Moghbel A, Agheli H, Kalantari E et al. Design and formulation of tragacanth dressing bandage for burn healing with no dermal toxicity. Toxicol Lett 2008; 180 (Suppl.) S154
    PubMedGoogle Scholar
  • 23 Nejatian M, Hatami M, Mohammadifar MA. Effect of gum tragacanth exuded by three Iranian Astragalus on mixed milk protein system during acid gelation. Int J Biol Macromol 2012;
    PubMedGoogle Scholar
  • 24 Krishnaiah YSR, Karthikeyan RS, Gouri Sankar V et al. Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride. J Controlled Release 2002; 81: 45-56
    CrossrefPubMedGoogle Scholar
  • 25 Krishnaiah YSR, Karthikeyan RS, Satyanarayana V. A three-layer guar gum matrix tablet for oral controlled delivery of highly soluble metoprolol tartrate. Int J Pharm 2002; 241: 353-366
    CrossrefPubMedGoogle Scholar
  • 26 Nerurkar J, Jun HW, Price JC et al. Controlled-release matrix tablets of ibuprofen using cellulose ethers and carrageenans: effect of formulation factors on dissolution rates. Eur J Pharm Biopharm 2005; 61: 56-68
    CrossrefPubMedGoogle Scholar
  • 27 Viridan A, Wittgren B, Larsson A. The consequence of the chemical composition of HPMC in matrix tablets on the release behaviour of model drug substances having different solubility. Eur J Pharm Biopharm 2011; 77: 99-110
    CrossrefPubMedGoogle Scholar
  • 28 Corti G, Cirri M, Maestrelli F et al. Sustained-release matrix tablets of metformin hydrochloride in combination with triacety-cyclodextrin. Eur J Pharm Biopharm 2008; 68: 303-309
    CrossrefPubMedGoogle Scholar
  • 29 Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001; 13: 123-133
    CrossrefPubMedGoogle Scholar
  • 30 Kravtchenko TP, Renoir J, Parker A et al. A novel method for determining the dissolution kinetics of hydrocolloid powders. Food Hydrocolloids 1999; 13: 219-225
    CrossrefPubMedGoogle Scholar
  • 31 Shan G, Igarashi K, Ooshima H. Dissolution kinetics of crystals in suspension and its application to l-aspartic acid crystals. Chem Eng J 2002; 88: 53-58
    CrossrefPubMedGoogle Scholar
  • 32 Wang Q, Ellis PR, Ross-Murphy SB. Dissolution kinetics of water-soluble polymers: The guar gum paradigm. Carbohydr Polym 2008; 74: 519-526
    CrossrefPubMedGoogle Scholar
  • 33 Adibkia K, Barzegar-Jalali M, Mohammadi G et al. Effect of sodium alginate chain length and Ca2+and Al 3+on the release of diltiazem from matrices. Pharmaceutical Sciences 2011; 16: 221-228
    PubMedGoogle Scholar
  • 34 Barzegar-Jalali M, Adibkia K, Valizadeh H et al. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci 2008; 11: 167-177
    PubMedGoogle Scholar
  • 35 Gafourian T, Safari A, Adibkia K et al. A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling. J Pharm Sci 2007; 96: 3334-3351
    CrossrefPubMedGoogle Scholar
  • 36 Javadzadeh Y, Ahadi F, Davaran S et al. Preparation and physicochemical characterization of naproxen-PLGA nanoparticles. Colloids Surf B Biointerfaces 2010; 81: 498-502
    CrossrefPubMedGoogle Scholar
  • 37 Mohammadi G, Barzegar-Jalali M, Siahi Shadbad MR et al. The effect of inorganic cations Ca2+ and Al3+ on the release rate of propranolol hydrochloride from sodium carboxymethylcellulose matrices. Daru 2009; 17
    PubMedGoogle Scholar
  • 38 Mohammadi G, Barzegar-Jalali M, Valizadeh H et al. Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone. J Pharm Pharm Sci 2010; 13: 152-161
    PubMedGoogle Scholar