The Influence of Fillers on Theophylline Release from Clay Matrices

Adeola O. Adebisi¹, Barbara R. Conway¹ and Kofi Asare-Addo^1,

¹Department of Pharmacy, School of Applied Science, University of Huddersfield, HD1 3DH, UK

Cite this paper:
Adeola O. Adebisi, Barbara R. Conway and Kofi Asare-Addo. The Influence of Fillers on Theophylline Release from Clay Matrices. American Journal of Pharmacological Sciences. 2015; 3(5):120-125. doi: 10.12691/ajps-3-5-3

Abstract

The objectives of this study were to investigate the suitability of magnesium aluminium silicate (MAS) (Veegum®) to control drug release of a model drug, theophylline, from tablet matrices. To this end, the performance of three commonly used fillers namely: lactose, microcrystalline cellulose (Avicel PH102; MCC), and pre-gelatinized starch, Starch 1500 PGS), were evaluated against Veegum®. The physico-mechanical properties of the tablet matrices were studied along with dissolution studies to determine the effect of single or binary mixtures of the excipients on the drug release pattern. A DSC hydration methodology was also employed to characterize the states of water present in the tablet matrices and to determine any impact on drug release. Formulations containing MAS alone produced compacts with the lowest hardness (4.5 kp) whereas formulations containing MCC alone produced the hardest tablets (17.2 kp). Dissolution studies suggested that matrices containing MAS alone released the theophylline quickest as compared to lactose, MCC or PGS. It was difficult to establish a trend of the bound and free water states in the tablet matrices; however the formulation containing only MAS had the highest bound water at 29 %. The results therefore show that theophylline does not interact with MAS. As such the dominant factor in controlling drug release using MAS requires interaction or intercalation with a cationic drug. In the absence of this however, other excipients can play a role in controlling drug release.

Keywords:
Veegum clay matrices DSC hydration magnesium aluminium silicate fillers

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References:

[1]	H. D. Williams, R. Ward, I. J. Hardy, and C. D. Melia, “The extended release properties of HPMC matrices in the presence of dietary sugars,” J Control Release, vol. 138, pp. 251-9, Sep 15 2009.
[2]	H. D. Williams, R. Ward, A. Culy, I. J. Hardy, and C. D. Melia, “Designing HPMC matrices with improved resistance to dissolved sugar,” Int J Pharm, vol. 401, pp. 51-9, Nov 30 2010.
[3]	H. D. Williams, R. Ward, I. J. Hardy, and C. D. Melia, “The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix,” Eur J Pharm Biopharm, vol. 76, pp. 433-6, Nov 2010.
[4]	S. R. Pygall, S. Kujawinski, P. Timmins, and C. D. Melia, “The suitability of tris(hydroxylmethyl) aminomethane (THAM) as a buffering system for hydroxypropyl methylcellulose (HPMC) hydrophilic matrices containing a weak acid drug,” International Journal of Pharmaceutics, vol. 387, pp. 93-102, 3/15/ 2010.
[5]	K. Asare-Addo, M. Levina, A. R. Rajabi-Siahboomi, and A. Nokhodchi, “Study of dissolution hydrodynamic conditions versus drug release from hypromellose matrices: the influence of agitation sequence,” Colloids Surf B Biointerfaces, vol. 81, pp. 452-60, Dec 1 2010.
[6]	K. Asare-Addo, W. Kaialy, M. Levina, A. Rajabi-Siahboomi, M. U. Ghori, E. Supuk, et al., “The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices--the use of the USP III apparatus,” Colloids Surf B Biointerfaces, vol. 104, pp. 54-60, Apr 1 2013.
[7]	K. Asare-Addo, A. O. Adebisi, and A. Nokhodchi, “Agitation Sequence and Ionic Strength on In-Vitro Drug Release from Hypromellose–The Influence of Compaction Force,” International Journal of Basic Medical Sciences and Pharmacy (IJBMSP), vol. 5, pp. 1-18, 2015.
[8]	A. Nokhodchi and K. Asare-Addo, “Drug release from matrix tablets: physiological parameters and the effect of food,” Expert Opin Drug Deliv, vol. 11, pp. 1401-18, Sep 2014.
[9]	M. R. Siahi-Shadbad, K. Asare-Addo, K. Azizian, D. Hassanzadeh, and A. Nokhodchi, “Release behaviour of propranolol HCl from hydrophilic matrix tablets containing psyllium powder in combination with hydrophilic polymers,” AAPS PharmSciTech, vol. 12, pp. 1176-82, Dec 2011.
[10]	A. Nokhodchi, S. Raja, P. Patel, and K. Asare-Addo, “The role of oral controlled release matrix tablets in drug delivery systems,” Bioimpacts, vol. 2, pp. 175-87, 2012.
[11]	A. Nokhodchi, D. Palmer, K. Asare-Addo, M. Levina, and A. Rajabi-Siahboomi, “Application of Polymer Combinations in Extended Release Hydrophilic Matrices,” in Handbook of Polymers for Pharmaceutical Technologies, ed: John Wiley & Sons, Inc., 2015, pp. 23-49.
[12]	S. Shojaee, K. Asare-Addo, W. Kaialy, A. Nokhodchi, and I. Cumming, “An investigation into the stabilization of diltiazem HCl release from matrices made from aged polyox powders,” AAPS PharmSciTech, vol. 14, pp. 1190-8, Sep 2013.
[13]	P. Timmins, S. R. Pygall, and C. D. Melia, Hydrophilic Matrix Tablets for Oral Controlled Release vol. 16. New York Springer, 2014.
[14]	R. C. Rowe, P. J. Sheskey, W. G. Cook, and M. E. Fenton, Handbook of Pharmaceutical Excipients, 7th ed. Washington DC: Pharmaceutical Press and American Pharmacists Association, 2012.
[15]	P. R. Laity, K. Asare-Addo, F. Sweeney, E. Šupuk, and B. R. Conway, “Using small-angle X-ray scattering to investigate the compaction behaviour of a granulated clay,” Applied Clay Science, vol. 108, pp. 149-164, 5// 2015.
[16]	T. Pongjanyakul, A. Priprem, and S. Puttipipatkhachorn, “Investigation of novel alginate−magnesium aluminum silicate microcomposite films for modified-release tablets,” Journal of Controlled Release, vol. 107, pp. 343-356, 10/3/ 2005.
[17]	S. W. Xu, J. P. Zheng, L. Tong, and K. D. Yao, “Interaction of functional groups of gelatin and montmorillonite in nanocomposite,” Journal of Applied Polymer Science, vol. 101, pp. 1556-1561, 2006.
[18]	J. P. Zheng, L. Luan, H. Y. Wang, L. F. Xi, and K. D. Yao, “Study on ibuprofen/montmorillonite intercalation composites as drug release system,” Applied Clay Science, vol. 36, pp. 297-301, 5// 2007.
[19]	T. Pongjanyakul and S. Rojtanatanya, “Use of Propranolol-Magnesium Aluminium Silicate Intercalated Complexes as Drug Reservoirs in Polymeric Matrix Tablets,” Indian Journal of Pharmaceutical Sciences, vol. 74, pp. 292-301, Jul-Aug 2012
[20]	M. S. Jhon and J. D. Andrade, “Water and hydrogels,” J Biomed Mater Res, vol. 7, pp. 509-22, Nov 1973.
[21]	S. Aoki, H. Ando, M. Ishii, S. Watanabe, and H. Ozawa, “Water behavior during drug release from a matrix as observed using differential scanning calorimetry,” Journal of Controlled Release, vol. 33, pp. 365-374, 3// 1995.
[22]	S. Yoshioka, Y. Aso, and T. Terao, “Effect of water mobility on drug hydrolysis rates in gelatin gels,” Pharm Res, vol. 9, pp. 607-12, May 1992.
[23]	S. Baumgartner, G. Lahajnar, A. Sepe, and J. Kristl, “Investigation of the state and dynamics of water in hydrogels of cellulose ethers by(1)H NMR spectroscopy,” AAPS PharmSciTech, vol. 3, pp. 86-93, 12/28
[24]	X. Mu, M. J. Tobyn, and J. N. Staniforth, “Development and evaluation of bio-dissolution systems capable of detecting the food effect on a polysaccharide-based matrix system,” J Control Release, vol. 93, pp. 309-18, Dec 12 2003.
[25]	H. Al-Hamidi, A. A. Edwards, D. Douroumis, K. Asare-Addo, A. M. Nayebi, S. Reyhani-Rad, et al., “Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling,” Colloids Surf B Biointerfaces, vol. 103, pp. 189-99, Mar 1 2013.
[26]	K. A. Khan, “The concept of dissolution efficiency,” Journal of Pharmacy and Pharmacology, vol. 27, pp. 48-49, 1975.
[27]	K. Asare-Addo, M. Levina, A. R. Rajabi-Siahboomi, and A. Nokhodchi, “Effect of ionic strength and pH of dissolution media on theophylline release from hypromellose matrix tablets-Apparatus USP III, simulated fasted and fed conditions,” Carbohydrate Polymers, vol. 86, pp. 85-93, 8/1/ 2011.
[28]	W. Kaialy, P. Emami, K. Asare-Addo, S. Shojaee, and A. Nokhodchi, “Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers,” Pharm Dev Technol, vol. 19, pp. 269-77, May 2014.
[29]	M. Levina and A. R. Rajabi-Siahboomi, “The influence of excipients on drug release from hydroxypropyl methylcellulose matrices,” J Pharm Sci, vol. 93, pp. 2746-54, Nov 2004.
[30]	A. Nokhodchi, A. Homayouni, W. Kaialy, R. Araya, K. Asare-Addo, and W. Obeidat, “Crystal engineering of ibuprofen using starch derivatives in crystallization medium to produce promising ibuprofen with improved pharmaceutical performance “ RSC Advances vol. 5, pp. 46119-46131, 2015.
[31]	K. Asare-Addo, B. R. Conway, H. Larhrib, M. Levina, A. R. Rajabi-Siahboomi, J. Tetteh, et al., “The effect of pH and ionic strength of dissolution media on in-vitro release of two model drugs of different solubilities from HPMC matrices,” Colloids Surf B Biointerfaces, vol. 111, pp. 384-91, Nov 1 2013.