INFLUENCE OF DRUG SOLUBILITY AND POLYMERS SUPPLY SOURCE ON THE PHYSICAL PERFORMANCE OF MATRIX TABLETS
Objective: The aim of this study is to explore the possible effects of drug solubility and commercial supply sources of HPMC and PVP on physical properties of matrix tablets.
Methods: Two different supply sources (A and B) for Hydroxy Propyl Methyl Cellulose (HPMC) as matrix forming polymer and Polyvinyl Pyrrilidone (PVP) as matrix supportive polymer were used with either Chlorphenaramine maleate (CPM), as a water soluble drug or Atenolol (ATN), as a water insoluble drug, to produce a series of matrix formulations using direct compression according to a 23 full factorial design. Matrices were then qualified for friability, hardness, and drug release attributes.
Results: Matrix hardness and friability properties demonstrated to be influenced by PVP supply source as an individual factor alone or in combination with drug solubility factor, moreover, both properties were found to be less affected by drug solubility and HPMC supply source, as individual factors. Compared to other factors, drug solubility was found to have a substantial influence on drug dissolution efficiency (DE) and diffusion exponent of the drug release (n) of different matrices.
Conclusion: Variation in commercial PVP supply source and drug solubility could possibly result in matrices with different physical performance.
2. Guo J-H, Skinner GW, Harcum WW, Barnum PE. Pharmaceutical applications of naturally occurring water-soluble polymers. Pharm Sci Technol 1998;1 Suppl 6:254-61.
3. Rogers TL. Hypromellose In: Rowe RC, Sheskey PJ, Quinn ME, editors. Handbook of Pharmaceutical Excipients. 6th ed. London: Pharmaceutical Press; 2009. p. 330-2.
4. Nikunj B, Modi D, Bhardia PD. Formulation, Development and evaluation of sustained release matrix tablets of repaglinide. Int J Pharm Res Bio-Sci 2014;3 Suppl 2:370-96.
5. Shoaib MH, Al Sabah Siddiqi S, Yousuf RI, Zaheer K, Hanif M, Rehana S, et al. Development and evaluation of hydrophilic colloid matrix of famotidine tablets. AAPS Pharm Sci Tech 2010;11 Suppl 2:708-18.
6. Tadros MI. Controlled-Release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitroâ€“in vivo evaluation in healthy human volunteers. Eur J Pharm Biopharm 2010;74 Suppl 2:332-9.
7. Saeio K, Pongpaibul Y, Viernstein H, Okonogi S. Factors influencing drug dissolution characteristic from hydrophilic polymer matrix tablet. Sci Pharm 2007;75:147-63.
8. Wise DL. Handbook of Pharmaceutical Controlled Release Technology. 1st ed. New York: Marcel Dekker Inc; 2005. p. 5-24.
9. Borguist P, Korner A, Larsson A. A Model for the drug release from a polymeric matrix tablets-effect of swelling and dissolution. J Control Rel 2006;113:216-25.
10. British Pharmacopoeia. Volume V, Appendices XVII G, H and XII B1. London: British Pharmacopoeia Commission; 2013. p. A487, A489, A332-A353.
11. British Pharmacopoeia. Volume III, Specific monographs. London: British Pharmacopoeia Commission; 2013. p. 2530, 2664.
12. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophillic polymers. Int J Pharm 1983;15:25-35.
13. Kumar MK, Shah MH, Ketkar A, Mahadik KR, Paradkar A. Effect of drug solubility and different excipients on floating behaviour and release from glyceryl monooleate matrices. Int J Pharm 2004;19 Suppl 272:151-60.
14. Realdon N, Ragazzi E. Effect of drug solubility on in vitro availability rate from suppositories with polyethylene glycol excipients. Pharm 2001;56 Suppl 2:163-7.
15. Pillay V, Fassihi R. Probing the dynamics of matrix hydration in the presence of electrolytes. Drug Deliv 2001;8 Suppl 2:87-92.
16. Peppas NA. Analysis of fickian and non-fickian drug release from polymers. Pharm Acta Helv 1985;60:110â€“11.
17. Ponchel G, Touchard F, Wouessidjewe D, DuchÃªne D, Peppas NA. Bioadhesive analysis of controlled-release systems. iii. bioadhesive and release behavior of metronidazole-containing poly (acrylic acid)-hydroxypropyl methylcellulose systems. Int J Pharm 1987;38:65-70.
18. Uko-Nne SD, Mendes RW, Jambhekar SS. Dried molasses as a direct compression matrix for oral controlled release drug delivery ii: release mechanism and characteristics of theophylline from a hpmc matrix. Drug Dev Ind Pharm 1989;15 Suppl 5:719-41.
19. Chakraborty S, Khandai M, Sharma A, Patra ChN, Patro VJ, Sen KK. Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from hpmc based matrix formulations. Acta Pharm 2009;59 Suppl 3:313-23.