Modulation of in-vitro drug-release from a HPMC matrix system: Potential role of a disintegrant

Sanjay Wagh, Jayanthi Suryakumar

Abstract


The objective of the current study was to investigate the role of disintegrants in modulation of drug release from HPMC-based hydrophilic matrices.  The polymer matrices of a water-soluble drug, Propranolol hydrochloride, were prepared in combination with different disintegrants by wet-granulation approach. The widely used superdisintegrants like crospovidone (CP), croscarmellose sodium (CCS), calcium carboxymethyl cellulose (CaCMC) and sodium starch glycolate (SSG) were investigated for their potential role as release modifiers. The polymer-disintegrant combinations were evaluated for in-vitro drug-release behaviour at various pH conditions coupled with determination of swelling behaviour and gel properties of matrices through texture analysis. The polymer-disintegrant combinations provided control over initial release rate and also exhibited complete drug release over 24 h. The work of penetration of hydrogels after 24 h dissolution study revealed that formulation with croscarmellose sodium showed complete relaxation of gel which fostered the complete drug release. Drug-release from the developed combination matrices was observed to be primarily Fickian diffusion based, except for combination of HPMC- sodium starch glycolate based matrices, where non-Fickian behaviour was observed. Barring sodium starch glycolate, all other polymer-disintegrant combinations provided pH-independent drug release. The accelerated stability studies of optimized HPMC-disintegrant matrix system were also satisfactory.  The results of this study suggest that a suitable disintegrant when used in combination with HPMC, could modulate the drug-release and also synergize the release-controlling properties of hydrogel matrix systems. These findings can certainly be applied to develop controlled-release hydrogel matrix system of other highly water-soluble drug candidates, and hold a great potential in development of cost-effective and stable HPMC-matrix systems with customized drug-release behaviour.  


Keywords


Propranolol hydrochloride, hydrophilic matrices, swelling, disintegrant, release kinetics.

Full Text:

PDF

References


Maderuelo C, Zarzuelo A and Lanao JM. Critical factors in the release of drugs from sustained release hydrophillic matrices. J. Control. Release, 2011;154: 2-19.

Gaetano L. Parametric simulation of drug release from hydrogel-based matrices. J Pharm Pharmacol, 2012; 4; 641:48-51.

Todd RH, Daniel SK. Hydrogels in drug delivery: Progress and challenges, Polymer, 2008; 49:1993-2007.

Siepmann J, Peppas NA. Modelling of drug release from delivery systems based on Hydroxypropyl Methylcellulose (HPMC). Adv Drug.Del, 2001; 48 2-3:139-157.

Hardy IJ, Windberg BA, Neri C, Byway PV, Booth SW, S Fitzpatrick. Modulation of drug release kinetics from Hydroxypropyl Methyl Cellulose matrix tablets using polyvinyl pyrrolidone. Int Journ Pharm, 2007; 337 1-2: 246-253.

Bendgude NT, Iyer VR and Poddar SIS. The Effects of Lactose, Microcrystalline Cellulose and Dicalcium Phosphate on Swelling and Erosion of Compressed HPMC Matrix Tablets: Texture Analyzer, Iranian Journal of Pharmaceutical Research, 2010; 9 4: 349-358.

Baveja SK, Ranga Rao KV, Devi KP. Zero-order release hydrophilic matrix tablets of β-adrenergic blockers. Int J Pharm, 1987; 39: 39–45.

Dabbagh MA, Ford JL, Rubinstein MH, Hogan JE, Rajabi-Siahboomi AR. Release of propranolol hydrochloride from matrix tablets containing sodium carboxymethylcellulose and Hydroxypropyl methylcellulose. Pharm Dev Technol, 1999; 4: 313-324.

Rao MY, Veni JK and Jayasagar G. Formulation and Evaluation of Diclofenac Sodium Using Hydrophilic Matrices. Drug Development and Industrial Pharmacy, 2001; 27,8, 759–766

Vaidya MP, Avachat AM. Investigation of the impact of insoluble diluents on the compression and release properties of matrix based sustained release tablets, Powder Technology, 2011; 214: 3-25, 375–381.

Qing RC, Yun WC, Jing HC, Beom JL. Formulation, release characteristics and bioavailability of novel monolithic Hydroxypropyl methylcellulose matrix tablets containing acetaminophen. Journal of Controlled Release, 2005;108: 351–361.

Zhao Na, Larry LA. The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharm Sci Tech, 2005; 6 1: E120-6.

Serlin MJ, Orme ML, Maclver M, Green GJ, Sibeon RG, and Breckenridge AM. The pharmacodynamics and pharmacokinetics of conventional and long-acting propranolol in patients with moderate hypertension, Br J Clin pharmacol, 1983;15,5: 519-527.

Atsushi K, Hirokazu T, Kunikazu M, Keiji Y. Improvement of HPMC tablet disintegration by the addition of inorganic salts. Chem. Pharm. Bull, 2008; 56, 4:598-601.

Oluwatoyin AO and Babatunde LA. Effect of the mode of incorporation on the disintegrant properties of acid modified water and white yam starches. Saudi Pharm J, 2012; 20,2: 171–175.

Sathe PM, Tsong Y, Shah VP. In-vitro dissolution profile comparison. In: Encyclopedia of Biopharmaceutical Statistics. New York: Marcel Dekker. 2003;456-462.

Khan KA. The concept of dissolution efficiency. J. Pharm. Pharmacol, 1975; 27: 48-49.

Themistocles PH, Gary DC, Michael AK, Panayotis EM. Quantitative Calculations in Pharmaceutical Practice and Research. VCH Publishers.Inc, New York. 1993; 345-348.

Bourne DWA. Pharmacokinetics. In Banker GS, Rhodes CT Modern Pharmaceutics, Eds., Marcel Dekker, New York, NY, USA, 4th edition; 2002. 67–92.

Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J.Pharm Sci, 1963;52: 1145-1149.

Richard WK, Robert G, Eric D, Pierre B, Nikolaos AP. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm, 1983; 15: 25-35.

Peniche C, Elvira C, Roman JS. Interpolymer complexes of chitosan and polymethacrylic derivatives of salicylic acid: Preparation, characterization and modification by thermal treatment. Polymer, 1998; 39:6549–6554.

Zhao Na, Augsberger LL Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution. AAPS PharmSci Tech, 2005; 6.

Mohamad A, Dashevsky A. pH independent pulsatile drug delivery system based on hard gelatin capsules and coated with aqueous dispersion Aquacoat ECD. Eur J Phar. Biopharm, 2006; 64, 173.

Gordon MS, Rudraraju VS, Dani K, Chowhan ZT. Effect of the mode of super disintegrant incorporation on dissolution in wet granulated tablets. J Pharm Sci, 1993; 82,2:220-6.

Omidian H, Park K. Swelling agents and devices in oral drug delivery. J Drug Del Sci Tech, 2008; 18,2: 83-93.

Mostafavi A, Emami J, Varshosaz J. Davies NM.

Rezazadeh M. Development of a prolonged-release gastroretentive tablet formulation of ciprofloxacin hydrochloride: Pharmacokinetic characterization in healthy human volunteers. International Journal of Pharmaceutics, 2011; 409: 128–136.

Paolo C, Ruggero B, Patrizia S, Nikolaos AP. Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance, Pharma Sci & Tech Today, 2000;3,6: 198–204.

Hongato Li, Xiaochen Gu. Correlation between drug dissolution and polymer hydration: A study using texture analysis. International Journal of Pharmaceutics. 2007; 342,1-2:18-25.


Refbacks

  • There are currently no refbacks.




Copyright (c) 2015 Sanjay Wagh

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

               AR Journals

18K, Street 1st, Gaytri Vihar, Pinto Park, Gwalior, M.P. India

Copyright@arjournals.org (Design) 2009-2021

 

Follow @arjournals on Twitter