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Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals

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Abstract

Purpose

Oral administration of Iodine−131 (I−131) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation.

Methods

Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs. The insulated HGCs were evaluated for their physicochemical characteristics and rupturing time in different dissolution media. HGCs internally lined with PS were examined for withstand loading with different volumes and radioactivities of I−131 solutions. Radioactivity release was studied in deionized water and acidic media. Quality control of released I−131 was inspected for radiochemical purities.

Results

There was a directly proportion between PS lining thickness and stability of HGCs after filling with 500 μl aqueous methylene blue solution. HGCs internally lined with PS 100 μm thickness withstand deformation for ˃ two months; however showed fast in-vitro rupturing time in different dissolution media. Internally lined HGCs loaded with different volumes and radioactivities of I−131 solutions resisted for one week without radioactive leakage. Yet, revealed complete release of I−131 after 20 min in dissolution media with great radiochemical purity.

Conclusion

The study promises safely I−131 aqueous solution delivery via adapted HGCs.

Oral administration of radiopharmaceuticals

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Abbreviations

FT-IR:

Fourier transform infrared spectroscopy

GC-MS:

Gas chromatography-mass spectroscopy

HGCs:

Hard gelatin capsules

I−131 :

Radioactive Iodine−131 solutions

MB:

Methylene blue

PS:

Polystyrene

References

  1. Saha GB. Characteristics of specific radiopharmaceuticals (chap. 7). Fundamentals of Nuclear Pharmacy 6th ed. New York: Springer; 2010. p. 115–52.

    Book  Google Scholar 

  2. Santos-Oliveira R, Antunes LJ. Radiopharmaceutical research and production in Brazil: a 30-year history of participation in the nuclear medicine scenario. J Nucl Med Technol. 2011;39(3):237–9.

    Article  Google Scholar 

  3. Garcia-Peña E, Caravalho J, Watkins JW, Leifer ES. Esophageal passage of iodine-131 capsules. J Nucl Med Technol. 1997;25(1):55–8.

    Article  Google Scholar 

  4. Kristensen K, Nørbygaard E, editors. Safety and efficacy of radiopharmaceuticals. 4. 1984th ed: pub. Springer Science & Business Media 2012. p. 85–98.

  5. Hung JC. Radioiodine dispensing and usage in a centralized hospital nuclear pharmacy. Thyroid. 1997;7(2):289–94.

    Article  CAS  Google Scholar 

  6. Kamalakkannan V, Puratchikody A, Masilamani K, Senthilnathan B. Solubility enhancement of poorly soluble drugs by solid dispersion technique–a review. J Pharm Res. 2010;3(9):2314–21.

    Google Scholar 

  7. Marques MR, Cole E, Kruep D, Gray V, Murachanian D, Brown WE, et al., editors. Liquid-filled gelatin capsules. Pharmacopeial forum; 2009.

  8. Kuentz M, Röthlisberger D. Determination of the optimal amount of water in liquid-fill masses for hard gelatin capsules by means of texture analysis and experimental design. Int J Pharm. 2002;236(1):145–52.

    Article  CAS  Google Scholar 

  9. Howard SS, Alexander S. Capsule containing a pharmaceutically useful radioactive material. U.S. patent no. 3,121,041. Washington, DC: U.S. Patent and Trademark Office; 1964.

    Google Scholar 

  10. Takada K, Murakami M. Glycyrrhizin preparations for transmucosal absorption. U.S. patent no. 6,890, vol. 547. Washington, DC: U.S. Patent and Trademark Office; 2005.

    Google Scholar 

  11. El-Aasser MS, Fitch RM. Future directions in polymer colloids: Springer Science & Business Media; 2012;138.

  12. Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol. 2010;21(5):733–5.

    Article  CAS  Google Scholar 

  13. Iconomopoulou S, Andreopoulou A, Soto A, Kallitsis J, Voyiatzis G. Incorporation of low molecular weight biocides into polystyrene–divinyl benzene beads with controlled release characteristics. J Control Release. 2005;102(1):223–33.

    Article  CAS  Google Scholar 

  14. Patil P, Paradkar A. Porous polystyrene beads as carriers for self-emulsifying system containing loratadine. AAPS PharmSciTech. 2006;7(1):E199–205.

    Article  Google Scholar 

  15. Maria AVW, Margarida MCO, Marcela Z, Ariane JSB, Mohammed Q, Ralph SO. Nanoradiopharmaceuticals for nanomedicine: building the future. Recent Pat Nanomed. 2014;4(2):90–4.

    Google Scholar 

  16. Sanagi MM, Lu LS, Nasir Z, Ibrahim WAW, Ahmedy AN. Determination of residual volatile organic compounds migrated from polystyrene food packaging into food simulant by headspace solid phase micro extraction-gas chromatography. Malaysian Journal of Analytical Sciences. 2008;12(3):542–51.

    Google Scholar 

  17. Rosell M, Ginebreda A, Barceló D. Simultaneous determination of methyl tert.-butyl ether and its degradation products, other gasoline oxygenates and benzene, toluene, ethylbenzene and xylenes in Catalonian groundwater by purge-and-trap-gas chromatography–mass spectrometry. J Chromatogr A. 2003;995(1):171–84.

    Article  CAS  Google Scholar 

  18. Perkasa DP, Erizal E, Darmawan D, Rasyid A. Effect of gamma irradiation on mechanical and thermal properties of fish gelatin film isolated from lates calcarifer scales. Indonesian Journal of Chemistry. 2013;13(1):28–35.

    Article  CAS  Google Scholar 

  19. Cilurzo F, Selmin F, Minghetti P, Montanari L, Lenardi C, Orsini F, et al. Comparison between gamma and beta irradiation effects on hydroxypropylmethylcellulose and gelatin hard capsules. AAPS PharmSciTech. 2005;6(4):E586–E93.

    Article  Google Scholar 

  20. Rockville M. Disintegration and dissolution of dietary supplements h2040i. USP USP 31–NF 262008. p. 732–6.

  21. IAEA-TECDOC M. 1340. Manual for reactor produced radioisotope. Vienna: International Atomic Energy Agency; 2003.

    Google Scholar 

  22. Roydan. United States pharmacopeia (USP 32) and the 27th edition of the national formulary (NF 27). Rockville: The United States Pharmacopeial Convention. Pustaka Kesehatan. 2008;2 (3):422–6.

  23. Socrates G. Six membered ring heterocyclic compounds, In: Infrared and Raman Characteristic Group Frequencies: Tables and Charts 3rd ed: Wiley 2001 p. 171.

  24. Ofner CM, Zhang YE, Jobeck VC, Bowman BJ. Crosslinking studies in gelatin capsules treated with formaldehyde and in capsules exposed to elevated temperature and humidity. J Pharm Sci. 2001;90(1):79–88.

    Article  CAS  Google Scholar 

  25. Suriyanarayanan S. Cywinski PJ, Moro A. J., Mohr G. J. and Kutner W. Chemosensors based on molecularly imprinted polymers. In: Haupt K, editor. molecular imprinting Top Curr Chem. 325: Springer Science & Business Media; 2012.

  26. Shepson P, Edney E, Corse E. Ring fragmentation reactions in the photooxidations of toluene and o-xylene. J Phys Chem. 1984;88(18):4122–6.

    Article  CAS  Google Scholar 

  27. Digenis GA, Gold TB, Shah VP. Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance. J Pharm Sci. 1994;83(7):915–21.

    Article  CAS  Google Scholar 

  28. Ellis B, Smith R. Oriented polystyrene sheet and film. In: Polymers: a property database. 2nd Ed. ed: CRC Press, Taylor & Francis Group; 2008. p. 327–8.

  29. Bullwinkel M, Gu J, Campbell G, Sukanek P. The effect of polymer molecular weight and solvent type on the planarization of spin-coated films. J Electrochem Soc. 1995;142(7):2389–94.

    Article  CAS  Google Scholar 

  30. Islam MM, Zaman A, Islam MS, Khan MA, Rahman MM. Physico-chemical characteristics of gamma-irradiated gelatin. Prog Biomater. 2014;3(1):21.

    Article  Google Scholar 

  31. Chiwele I, Jones BE, Podczeck F. The shell dissolution of various empty hard capsules. Chem Pharm Bull. 2000;48(7):951–6.

    Article  CAS  Google Scholar 

  32. Zhang X, Do MD, Casey P, Sulistio A, Qiao GG, Lundin L, et al. Chemical cross-linking gelatin with natural phenolic compounds as studied by high-resolution NMR spectroscopy. Biomacromolecules. 2010;11(4):1125–32.

    Article  CAS  Google Scholar 

  33. Mercade-Prieto R, Sahoo PK, Falconer RJ, Paterson WR, Wilson DI. Polyelectrolyte screening effects on the dissolution of whey protein gels at high pH conditions. Food Hydrocoll. 2007;21(8):1275–84.

    Article  CAS  Google Scholar 

  34. Duconseille A, Astruc T, Quintana N, Meersman F, Sante-Lhoutellier V. Gelatin structure and composition linked to hard capsule dissolution: a review. Food Hydrocoll. 2015;43:360–76.

    Article  CAS  Google Scholar 

  35. Yang XJ, Zheng PJ, Cui ZD, Zhao NQ, Wang YF, De Yao K. Swelling behaviour and elastic properties of gelatin gels. Polym Int. 1997;44(4):448–52.

    Article  CAS  Google Scholar 

  36. Miyawaki O, Norimatsu Y, Kumagai H, Irimoto Y, Kumagai H, Sakurai H. Effect of water potential on sol-gel transition and intermolecular interaction of gelatin near the transition temperature. Biopolymers. 2003;70(4):482–91.

    Article  CAS  Google Scholar 

  37. Swidan M, Sakr T, Motaleb M, El-Bary AA, El-Kolaly M. Preliminary assessment of radioiodinated fenoterol and reproterol as potential scintigraphic agents for lung imaging. J Radioanal Nucl Chem. 2015;303(1):531–9.

    Article  CAS  Google Scholar 

  38. Swidan M, Sakr T, Motaleb M, El-Bary AA, El-Kolaly M. Radioiodinated acebutolol as a new highly selective radiotracer for myocardial perfusion imaging. J Label Compd Radiopharm. 2014;57(10):593–9.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt

    Samia Mohamed Omar

  2. Department of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, 11795, Egypt

    Samia Mohamed Omar & Rania Safaa Abdel-Rashid

  3. Ministry of Interior, Medical Services, Cairo, Egypt

    Mohamed Kamal AlAssaly

  4. Faculty of Pharmacy, October University of Modern Sciences and Arts, Cairo, Egypt

    Tamer M. Sakr

  5. Radioactive Isotopes and Generators, Atomic Energy Authority, Cairo, Egypt

    Tamer M. Sakr

Authors
  1. Samia Mohamed Omar
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  2. Rania Safaa Abdel-Rashid
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  3. Mohamed Kamal AlAssaly
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  4. Tamer M. Sakr
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Correspondence to Rania Safaa Abdel-Rashid or Tamer M. Sakr.

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Omar, S.M., Abdel-Rashid, R.S., AlAssaly, M.K. et al. Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals. DARU J Pharm Sci 27, 295–305 (2019). https://doi.org/10.1007/s40199-019-00275-2

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  • DOI: https://doi.org/10.1007/s40199-019-00275-2

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