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Characterization of crosslinked hard gelatin capsules for a structural assembly of elementary osmotic pump delivery system

  • Chaowalit Monton
  • Poj KulvanichEmail author
Original Article
  • 6 Downloads

Abstract

The objective of this study was to characterize the crosslinked hard gelatin capsules (HGCs) for use as a structural assembly of elementary osmotic pumps (EOP). HGCs were crosslinked in formaldehyde vapor for 6, 12, and 24 h. Weight loss after immersing in various mediums, water soluble protein fraction, loss on drying, and formaldehyde residue were investigated. Fourier transform infrared (FTIR) spectra were used to detect the crosslinking formation. The EOP capsules were prepared for delivery of diltiazem hydrochloride (DIL HCl) and ambroxol hydrochloride (AMB HCl), which are freely and sparingly water soluble drugs, respectively. Physicochemical stability of storage crosslinked HGC shells was investigated. All crosslinked HGC shells were water insoluble. FTIR spectra exhibited intermediate lysine methylol and arginine methylol peaks. Storage time increased, moisture content increased and formaldehyde residue decreased. The developing EOP capsules were more appropriate for delivery of high water soluble rather than low water soluble drug. EOP capsule contained 100 mg DIL HCl using HGCs crosslinked for 12 h provided release profiles for 12 h with a lag time of 2.6–3.1 h. It was also found that DIL HCl EOP capsules prepared using crosslinked HGC shells stored for 90 days maintained the similar drug release profiles. AMB HCl EOP capsules exhibited low drug release. In summary, the crosslinked HGCs were applicable as a structural assembly of the osmotic controlled drug delivery system.

Keywords

Crosslinked hard gelatin capsules Structural assembly Elementary osmotic pumps 

Notes

Acknowledgements

The authors greatly appreciate Graduate School and College of Pharmacy, Rangsit University for financial support. We would like to acknowledge Biolab Co., Ltd., Thailand, Siam Pharmaceutical Co., Ltd., Thailand, Capsules Products Co., Ltd., Thailand, Onimax Co., Ltd., Thailand, Sun Herb Thai Chinese Manufacturing, Thailand, and Colorcon Inc., USA for contribution of some drugs, chemicals, and materials in this study. The authors are grateful to Professor J. E. Moreton, School of Pharmacy, University of Maryland at Baltimore, for his comments, assistance in reading and editing the manuscript.

Compliance with ethical standards

Conflict of interest

All authors (C. Monton and P. Kulvanich) declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

  1. Augsburger LL (2009) Hard- and soft-shell capsules. In: Florence AT, Siepmann J (eds) Modern pharmaceutics-basic principles and systems, 5th edn. CRC Press, Florida, p 511Google Scholar
  2. Chauhan CS, Ranawat MS, Choudhury PK (2007) Fabrication and evaluation of asymmetric membrane osmotic pump. Ind J Pharm Sci 69:748–752CrossRefGoogle Scholar
  3. Chiwele I, Jones BE, Podczeck F (2000) The shell dissolution of various empty hard capsules. Chem Pharm Bull (Tokyo) 48:951–956CrossRefGoogle Scholar
  4. Colorcon (2012) Polyox™ water soluble resins. https://www.colorcon.com/products-formulation/all-products/download/782/2124/34?method=view. Accessed 2 Apr 2015
  5. Conley R, Gupta SK, Sathyan G (2006) Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin 22:1879–1892.  https://doi.org/10.1185/030079906x132613 CrossRefGoogle Scholar
  6. Davar N, Barcley B, Gupta S (2008) Osmotic systems. In: Augsburger LL, Hoag SW (eds) Pharmaceutical dosage forms: tablets, 3rd edn. Informa Healthcare, New York, pp 493–507CrossRefGoogle Scholar
  7. Derakhshandeh K, Berenji MG (2014) Development and optimization of buspirone oral osmotic pump tablet. Res Pharm Sci 9:233–241Google Scholar
  8. Gobade N, Koland M, Harish K (2012) Asymmetric membrane osmotic capsules for terbutaline sulphate. Ind J Pharm Sci 74:69–72.  https://doi.org/10.4103/0250-474x.102546 CrossRefGoogle Scholar
  9. Guan J, Zhou L, Pan Y, Han H, Xu H, Pan W (2010) A novel gastro-retentive osmotic pump capsule using asymmetric membrane technology: in vitro and in vivo evaluation. Pharm Res 27:105–114.  https://doi.org/10.1007/s11095-009-9984-1 CrossRefGoogle Scholar
  10. Higuchi T, Leeper HM (1976) Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient. US patent no.3995631Google Scholar
  11. ICH Expert Working Group (2015) Addendum to ICH M7: assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk: Application of the principles of the ICH M7 guideline to calculation of compound-specific acceptable intakes M7(R1). Accessed 10 Oct 2018Google Scholar
  12. Liu L, Ku J, Khang G, Lee B, Rhee JM, Lee HB (2000) Nifedipine controlled delivery by sandwiched osmotic tablet system. J Control Release 68:145–156.  https://doi.org/10.1016/S0168-3659(00)00243-1 CrossRefGoogle Scholar
  13. Liu D, Yu S, Zhu Z, Lyu C, Bai C, Ge H, Yang X, Pan W (2014) Controlled delivery of carvedilol nanosuspension from osmotic pump capsule: in vitro and in vivo evaluation. Int J Pharm 475:496–503.  https://doi.org/10.1016/j.ijpharm.2014.09.008 CrossRefGoogle Scholar
  14. Salsa T, Pina ME, Teixeira-Dias JJC (1996) Crosslinking of gelatin in the reaction with formaldehyde: an FT-IR spectroscopic study. Appl Spectrosc 50:1314–1318.  https://doi.org/10.1366/0003702963904881 CrossRefGoogle Scholar
  15. Santus G, Baker RW (1995) Osmotic drug delivery: a review of the patent literature. J Control Release 35:1–21.  https://doi.org/10.1016/0168-3659(95)00013-X CrossRefGoogle Scholar
  16. Singh S, Rao KVR, Venugopal K, Manikandan R (2002) Alteration in dissolution characteristics of gelatin-containing formulations: a review of the problem, test methods, and solutions. Pharm Technol 26:36–58Google Scholar
  17. Sonkar A, Kumar A, Pathak K (2016) Cellulose acetate 398–10 asymmetric membrane capsules for osmotically regulated delivery of acyclovir. J Pharm 2016:12.  https://doi.org/10.1155/2016/8471520 Google Scholar
  18. Tengroth C, Gasslander U, Andersson FO, Jacobsson SP (2005) Cross-linking of gelatin capsules with formaldehyde and other aldehydes: an FTIR spectroscopy study. Pharm Dev Technol 10:405–412.  https://doi.org/10.1081/pdt-65693 CrossRefGoogle Scholar
  19. Theeuwes F (1975) Elementary osmotic pump. J Pharm Sci 64:1987–1991.  https://doi.org/10.1002/jps.2600641218 CrossRefGoogle Scholar
  20. US Environmental Protection Agency (2000) Formaldehyde. http://www3.epa.gov/airtoxics/hlthef/formalde.html. Accessed 7 Jan 2016
  21. US Environmental Protection Agency (2001) Formaldehyde. http://www.euro.who.int/__data/assets/pdf_file/0014/123062/AQG2ndEd_5_8Formaldehyde.pdf. Accessed 23 Jun 2015
  22. Verma RK, Mishra B, Garg S (2000) Osmotically controlled oral drug delivery. Drug Dev Ind Pharm 26:695–708.  https://doi.org/10.1081/ddc-100101287 CrossRefGoogle Scholar
  23. Walker JM (2002) The bicinchoninic acid (BCA) assay for protein quantitation. In: Walker JM (ed) The protein protocols handbook. Humana Press, New Jersey, pp 11–14CrossRefGoogle Scholar
  24. Waterman KC, Goeken GS, Konagurthu S, Likar MD, MacDonald BC, Mahajan N, Swaminathan V (2011) Osmotic capsules: a universal oral, controlled-release drug delivery dosage form. J Control Release 152:264–269.  https://doi.org/10.1016/j.jconrel.2011.02.001 CrossRefGoogle Scholar
  25. Wichianprasit N, Kulvanich P (2009) Osmotically controlled drug delivery system using a crosslinked and non-crosslinked hard gelatin capsule. Abstracts, Asian Federation of Pharmaceutical Sciences Conference, Fukuoka, Japan. p 193Google Scholar
  26. Wong PSL, Gupta SK, Stewart BE (2003) Osmotically controlled tablets. In: Rathbone MJ, Hadgraft J, Roberts MS (eds) Modified-release drug delivery technology, 2nd edn. Informa Healthcare, New York, pp 101–114Google Scholar
  27. Yang Y, Zhao Z, Wang Y, Yang L, Liu D, Yang X, Pan W (2016) A novel asymmetric membrane osmotic pump capsule with in situ formed delivery orifices for controlled release of gliclazide solid dispersion system. Int J Pharm 506:340–350.  https://doi.org/10.1016/j.ijpharm.2016.04.061 CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  1. 1.College of PharmacyRangsit UniversityPathum ThaniThailand

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