Polymers in Medicine

Polim. Med.
Index Copernicus (ICV 2022) – 121.55
MEiN – 70
Average rejection rate – 39.13%
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

Download PDF

Polymers in Medicine

2016, vol. 46, nr 1, January-June, p. 5–15

doi: 10.17219/pim/62511

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Creative Commons BY-NC-ND 3.0 Open Access

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs

Neha Dhiman1,A,B,C,F, Rajendra Awasthi1,A,B,C,D,E,F, Shammy Jindal1,A,B,C,F, Smriti Khatri2,A,B,C,E,F, Kamal Dua3,4,A,B,C,E,F

1 Department of Pharmaceutics, Laureate Institute of Pharmacy, Kathog, Tehsil-Dehra, Distt-Kangra, Himachal Pradesh, India

2 Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India

3 School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India

4 School of Pharmacy and Biomedical Sciences, University of Newcastle, Newcastle, Callaghan NSW, Australia

Abstract

Background. The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose.
Objectives. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin.
Material and Methods. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation.
Results. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h).
Conclusion. Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Key words

sustained release, release kinetics, bilayer tablet, incompatible, conventional release

References (15)

  1. Singh B., Kapil R., Nandi M., Ahuja N.: Developing oral drug delivery systems using formulation by design: Vital precepts, retrospect and prospects. Expert Opin. Drug Deliv. 2011, 8 (10), 1342–1360.
  2. Deshpande R.D., Gowda D.V., Nawaz Md N., Maramwar D.N.: Bilayer tablets – an emerging trend: A review. Int. J. Pharm. Sci. Res. 2011, 2 (10), 2534–2544.
  3. Nilawar P.S., Wankhade V.P., Badnag D.B.: An emerging trend on bilayer tablets. Int. J. Pharm. Sci. Res. 2013, 3 (1), 15–21.
  4. Niwa M., Hiraishi Y., Iwasaki N., Terada K.: Quantitative analysis of the layer separation risk in bilayer tablets using terahertz pulsed imaging. Int. J. Pharm. 2013, 452 (1–2), 249–256.
  5. Abebe A., Martin K., Patel J., Desai D., Timmins P.: Bilayer tablet formulations. 2013, US Patent No. 8,535,715.
  6. Abebe A., Akselib I., Sprockel O., Kottala N., Cuitino A.M.: Review of bilayer tablet technology. Int. J. Pharm. 2014, 461 (1–2), 549–558.
  7. Vaithiyalingam S.R, Sayeed V.A.: Critical factors in manufacturing multi-layer tablets – Assessing material attributes, inprocess controls, manufacturing process and product performance. Int. J. Pharm. 398, 2010, 9–13
  8. Kottala N., Abebe A., Sprockel O., Bergum J., Nikfar F., Cuitino A.M.: Evaluation of the performance characteristics of bilayer tablets: Part I. impact of material properties and process parameters on the strength of bilayer tablets. AAPS PharmSciTech 2012, 13 (4), 1236–1242.
  9. Charman S.A., Charman W.N.: Oral modified-release delivery systems. [In:] Modified-release drug delivery technology. Eds.: Rathbone M.J., Roberts M.S., Hadgraft J. Marcel Dekker Inc, New York 2003, Vol. 126, 1–10.
  10. Kohlrausch A.: Bilayer tablet of telmisartan and simvastatin. United States patent. US 20060078615 A1. 2006 Apr 13.
  11. Vaghasiya H., Solanki N., Upadhyay P., Shah S.: Formulation development and optimization of bilayered floating tablet of diltiazem hydrochloride. Ph. Tech. Med. 2013, 2 (6), 408–413.
  12. United states Pharmacopoeia and National Formulary (USP 24-NF 19), National Publishing, Philadelphia, PA, 2000.
  13. Wienen W., Entzeroth M., van Meel J.C.A., Stangier J., Busch U., Ebner T., Schmid J., Lehmann H., Matzek K., KempthorneRawson J., Gladigau V., Hauel N.H.: A Review on telmisartan: A novel, long-acting angiotensin ii-receptor antagonist. Cardiovasc. Drug Rev. 2000, 18 (2), 127–154.
  14. Arayne M.S., Sultana N., Haroon U., Zaidi B.: In vitro evidences for simvastatin and losartan potassium interaction and its in vivo implications. J. Chil. Chem. Soc. 2009, 54, (4), 432–436.
  15. United States pharmacopoeia and National Formulary (USP 30-NF 25), United States Pharmacopeial Convention, Rockville, 1995.