A Novel Composite Membrane for pH Responsive Permeation

Document Type : Original Article


1 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmaceutics, School of Chemical Engineering, Sharif University, Tehran, Iran

4 Department of Pharmaceutics, School of Pharmacy, University of Toronto, Toronto, Canada


In this study, a kind of pH sensitive composite membrane was prepared and drug permeation through it was investigated in terms of pH. Rationale of this study originated from the fact that a pH change which may be a result of a disease state in the body can trigger drug release.
Materials and Methods
 Here, a kind of pH sensitive composite membrane containing different nanoparticle [1:1 n-isopropyl acrylamide (Nipam): metacrylic acid (Maa)] contents in ethylcellulose was prepared by a casting method. Swelling ratios of these nanoparticles and composite membranes with different particle loadings were determined. Permeation of two different drug models with different hydrophilicity and molecular weights, vitamin B12 (vit B12) and paracetamol, through these membranes was studied in terms of pH.
 It was seen that swelling ratios of nanoparticles and the composite membranes went up as the particle content increased at each pH. Vit B12 and paracetamol permeation through the membranes in pH value below the pKa was much higher than that at pHs above it, but this difference was much more pronounced for vit B12 compared to paracetamol.
Permeation through these membranes showed a sharp sensitivity to pH changes. Nanoparticles in the composite membranes could act as nanovalves due to their sharp swelling/shrinkage around the pKa of Maa. These membranes could be considered as an ideal stimuli-sensitive barrier for modulating drug release with a small change in pH.


1. Emanuele AD. Responsive polymeric delivery systems.  Clin Pharmacokinet 1996; 31:241-245.
2. Sadeghi F, Afrasiabi Garekani H, Hajiaghapoor N. Evaluation of Eudragit RS and RL solid dispersion systems in preparation of diclofenac sodium sustained release matrices. Tabriz J  Pharm Sci  2003; 49- 62.
3. Eddington D T, Beebe  D J. Flow control with hydrogels. Adv Drug Deliv Rev 2004; 56:199-210.
4. Yam F, Wu XY, Zhang Q. A novel Composite Membrane for temperature and pH- responsive permeation. Am Chem Soc  2000; 26:263-272.
5. Yam F. Development of a temperature and pH responsive membrane system for regulated drug release, Ph.D thesis 1999; 1-10.
6. Dinarvand R, Khodaverdi E, Atyabi F. Temperature-sensitive permeation of methimazole through cyano-biphenyl liquid crystals embedded in cellulose nitrate membranes. Mol Cryst Liq Cryst 2005; 442:19-30.
7. Atyabi F, Khodaverdi E, Dinarvand R. Temperature modulated drug permeation through a liquid crystal entrapped membrane. Int J Pharm 2007; 339: 213-221.
8. Peppas N A, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 2000; 50: 27-46.
9. Lin CC, Metters AT. Hydrogels in controlled release formulations: Network design and mathematical modeling. Adv Drug Deliv Rev 2006; 58:1379-1408.
10. Kikuchi A, Okano T. Pulsatile drug release control using hydrogels. Adv Drug Deliv Rev 2002; 54:53-77.
11. Qui Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 2001; 53:321-339.
12. Gudeman LF, Peppas V. pH-sensitive membranes from poly (vinyl alcohol)/poly (acrylic acid) interpenetrating networks. J Mem Sci 1995;107:239-248.
13. Turner J S, Cheng YL. Heterogeneous polyelectrolyte gels as stimuli – responsive membranes. J Mem Sci 1998; 148:207-222.
 14. Brazel CS, Peppas NA. Modeling of drug release from swellable polymers. Eur J Pharm Biopharm  2000; 49: 47-58.
15. Jeong B, Gutowska A. Lessons from nature: stimuli-responsive polymers and their biomedical applications. Trends Biotechnol 2002; 207:306-311.
16. Zhang K, Wu XY. Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptids. Biomaterials  2004; 25:5281-5291.
17. Feil H,  Bae YH, Feijen J, Kim SW. Mutual influence of pH and temperature on the swelling of ionizable and thermosensitive hydrogels. Macromol 1992; 52:5528-5530.
18. Wu XY, Lee PI. Preparation and characterization of pH- sensitive nanospheres. Pharm Res 1993; 10:1544-1547.
19. Khodaverdi E, Rajabi O, Salari  R, Abdekhodai  M J, Wu  XY. pH – Sensitive permeation through NIPPAM:MAA composite membranes, The Third Iranian Conference of  Novel Drug Delivery Systems, Tehran, Iran, 2007.