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A Novel Technique to Improve Drug Loading Capacity of Fast/Extended Release Orally Dissolving Films with Potential for Paediatric and Geriatric Drug Delivery

Abstract

Orally dissolving films (ODFs) have received much attention as potential oral drug delivery systems for paediatric and geriatric patients, particularly those suffering from dysphagia. With their unique properties and advantages, the technology offers improved patient compliance and wider acceptability, eliminates the fear of choking, enables ease of administration and offers dosing convenience, without the requirement of water. However, adequate drug loading remains a challenge. The aim of this study was to mechanistically design and evaluate fast and extended release ODF formulations with high drug loading capacity, displaying good physicochemical and mechanical properties, as a potential dosage form for paediatric and geriatric use employing a slightly soluble model drug—ibuprofen. Different polymers (0.6–10% HPMC, 0.6–1.5% guar gum), plasticisers (0.1–0.5% glycerine, 0.1% sorbitol) and processing conditions (40–60°C drying temperatures, 8–16 h drying times) were investigated to produce films using the solvent casting method. Molecular compatibility was assessed using TGA, XRD and FTIR whereas film topography was assessed using SEM. Maximum ibuprofen load in single films was 20.7 mg/film (54.4%) and released 100% drug content in 5 min, while triple layered ibuprofen-loaded films contained 62.2 mg/film and released 100% drug release in 1 h. The ODFs demonstrated good disintegration time using low volume artificial saliva media and high dosage from uniformity. This study provides a mechanistic insight to the design and evaluation of fast and extended release ODFs with high drug loading, suitable for administration to paediatric and geriatric patients.

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References

  1. Mandeep K, Rana AC, Nimrata S. Fast dissolving films : an innovative drug delivery system 2013;2(1):14–24.

  2. Bhyan B, Jangra S, Kaur M, Singh H. Orally fast dissolving films: innovations in formulation and technology. Int J Pharm Sci Rev Res. 2011;9(2):9–15.

    Google Scholar 

  3. Preis M. Orally disintegrating films and mini-tablets—innovative dosage forms of choice for pediatric use. AAPS PharmSciTech. 2015;16(2):234–41. Available from:. https://doi.org/10.1208/s12249-015-0313-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Irfan M, Rabel S, Bukhtar Q, Imran M, Jabeen F, Khan A. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharm J. 2016;24(5):537–46.

    Article  Google Scholar 

  5. Londhe V, Shirsat R. Formulation and characterization of fast-dissolving sublingual film of iloperidone using Box–Behnken design for enhancement of oral bioavailability. AAPS PharmSciTech. 2018;19(3):1392–400. Available from:. https://doi.org/10.1208/s12249-018-0954-y.

    CAS  Article  PubMed  Google Scholar 

  6. Montenegro-Nicolini M, Morales JO. Overview and future potential of buccal mucoadhesive films as drug delivery systems for biologics. AAPS PharmSciTech. 2017;18(1):3–14. Available from:. https://doi.org/10.1208/s12249-016-0525-z.

    CAS  Article  PubMed  Google Scholar 

  7. Gala RP, Popescu C, Knipp GT, McCain RR, Ubale RV, Addo R, et al. Physicochemical and preclinical evaluation of a novel buccal measles vaccine. AAPS PharmSciTech. 2017;18(2):283–92. Available from:. https://doi.org/10.1208/s12249-016-0566-3.

    CAS  Article  PubMed  Google Scholar 

  8. El-Setouhy DA, El-Malak NSA. Formulation of a novel tianeptine sodium orodispersible film. AAPS PharmSciTech. 2010;11(3):1018–25.

    CAS  Article  Google Scholar 

  9. Song Q, Guo X, Sun Y, Yang M. Anti-solvent precipitation method coupled electrospinning process to produce poorly water-soluble drug-loaded orodispersible films. AAPS PharmSciTech. 2019;20(7):273. Available from:. https://doi.org/10.1208/s12249-019-1464-2.

    CAS  Article  PubMed  Google Scholar 

  10. Alsofany JM, Hamza MY, Abdelbary AA. Fabrication of nanosuspension directly loaded fast-dissolving films for enhanced oral bioavailability of olmesartan medoxomil: in vitro characterization and pharmacokinetic evaluation in healthy human volunteers. AAPS PharmSciTech. 2018;19(5):2118–32. Available from:. https://doi.org/10.1208/s12249-018-1015-2.

    CAS  Article  PubMed  Google Scholar 

  11. Patil P, Shrivastava SK. Fast dissolving oral films: a novel drug delivery system. Int J Sci Res. 2014;3(7):2088–93.

    Google Scholar 

  12. Preis M, Pein M, Breitkreutz J. Development of a taste-masked orodispersible film containing dimenhydrinate 2012;4(4):551–62.

  13. Hirpara F, Debnath SK, Saisivam S. Optimization & screening of different film forming polymers and plasticizers in fast dissolving sublingual film. Int J Pharm Pharm Sci. 2014;6(6):41–2.

    Google Scholar 

  14. ElMeshad AN, El Hagrasy AS. Characterization and optimization of orodispersible mosapride film formulations. AAPS PharmSciTech. 2011;12(4):1384–92.

    CAS  Article  Google Scholar 

  15. Thakur N, Bansal M, Sharma N. Overview “a novel approach of fast dissolving films and their patients.” 2013;7(2):50–8.

  16. Kande KV, Kotak DJ, Degani MS, Kirsanov D, Legin A, Devarajan PV. Microwave-assisted development of orally disintegrating tablets by direct compression. AAPS PharmSciTech. 2017;18(6):2055–66. Available from:. https://doi.org/10.1208/s12249-016-0683-z.

    CAS  Article  PubMed  Google Scholar 

  17. Sharma D, Kaur D, Verma S, Singh D, Singh M, Singh G. Fast dissolving oral films technology: a recent trend for an innovative oral drug delivery system. Int J Drug Deliv. 2015;7:60–75.

    CAS  Google Scholar 

  18. Tomar A, Sharma K, Chauhan NS, Mittal A, Bajaj U. Formulation and evaluation of fast dissolving oral film of dicyclomine as potential route of buccal delivery. Int J Drug Dev Res. 2012;4(2):408–17.

    CAS  Google Scholar 

  19. Borges AF, Silva C, Coelho JFJ, Simões S. Oral films: current status and future perspectives: I—galenical development and quality attributes. J Control Release. 2015;206:1–19.

    CAS  Article  Google Scholar 

  20. Kulkarni A, Deokule H, Mane M, Ghadge D. Exploration of different polymers for use in the formulation of oral fast dissolving strips. J Curr Pharm Res. 2010;2(1):33–5.

    Google Scholar 

  21. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control Release. 2009;139(2):94–107.

    CAS  Article  Google Scholar 

  22. Dahmash EZ, Al-Khattawi A, Iyire A, Al-Yami H, Dennison TJ, Mohammed AR. Quality by design (QbD) based process optimisation to develop functionalised particles with modified release properties using novel dry particle coating technique. PLoS One. 2018;13(11):e0206651.

    Article  Google Scholar 

  23. Ding C, Zhang M, Li G. Preparation and characterization of collagen/hydroxypropyl methylcellulose (HPMC) blend film. Carbohydr Polym. 2015;119:194–201 Available from: http://www.sciencedirect.com/science/article/pii/S0144861714011709.

    CAS  Article  Google Scholar 

  24. Liew K Bin, Tze Y, Tan F, Peh KK. Characterization of oral disintegrating film containing donepezil for Alzheimer disease 2012;13(1):134–42.

  25. FDA. Food Additive Status List [Internet]. 2019 [cited 2020 Feb 16]. Available from: https://www.fda.gov/food/food-additives-petitions/food-additive-status-list#ftnG.

  26. Cervera MF, Heinämäki J, Krogars K, Jörgensen AC, Karjalainen M, Colarte AI, et al. Solid-state and mechanical properties of aqueous chitosan-amylose starch films plasticized with polyols. AAPS PharmSciTech. 2004;5(1):109.

    PubMed Central  Google Scholar 

  27. ICH. Validation of analytical procedures: text and methodology Q2(R1). Int Conf Harmon Tech Requir Regist Pharm Hum Use [Internet]. 2005;4. Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf.

  28. Koland M, Charyulu RN, Vijayanarayana K, Prabhu P. In vitro and in vivo evaluation of chitosan buccal films of ondansetron hydrochloride. Int J Pharm Investig. 2011;1(3):164–71.

    CAS  Article  Google Scholar 

  29. Ph.Eur. European pharmacopoeia. Vol. 1. Council of Europe; 2010.

  30. Saab M, Mehanna MM. Disintegration time of orally dissolving films: various methodologies and in-vitro/in-vivo correlation. Die Pharm Int J Pharm Sci. 2019;74(4):227–30.

    CAS  Google Scholar 

  31. USP-35. The United States pharmacopeia: the National Formulary : USP 35 NF 30th Edition. Authority of the United States Pharmacopeial Convention I, editor. Washington, D.C. Rockville: USP, C. (2011). The United States Pharmacopeia. National Formulary.; 2011.

  32. Bala R, Khanna S, Pawar P, Arora S. Orally dissolving strips: a new approach to oral drug delivery system. Int J Pharm Investig. 2013;3(2):67–76.

    CAS  Article  Google Scholar 

  33. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen: a practitioner-based randomized clinical trial. Jama. 1995;273(12):929–33.

    CAS  Article  Google Scholar 

  34. Baloğlu E, Karavana SY, Hyusein IY, Köse T. Design and formulation of Mebeverine HCl semisolid formulations for intraorally administration. AAPS PharmSciTech. 2010;11(1):181–8. Available from:. https://doi.org/10.1208/s12249-009-9374-3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Liu ZQ, Yi X-S, Feng Y. Effects of glycerin and glycerol monostearate on performance of thermoplastic starch. J Mater Sci. 2001;36(7):1809–15.

    CAS  Article  Google Scholar 

  36. Crnkovic PM, Koch C, Ávila I, Mortari DA, Cordoba AM, Moreira dos Santos A. Determination of the activation energies of beef tallow and crude glycerin combustion using thermogravimetry. Biomass and Bioenergy. 2012;44:8–16 Available from: http://www.sciencedirect.com/science/article/pii/S0961953412001845.

    CAS  Article  Google Scholar 

  37. Dian L, Yang Z, Li F, Wang Z, Pan X, Peng X, et al. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study. Int J Nanomedicine. 2013;8:845.

    PubMed  PubMed Central  Google Scholar 

  38. Storey RA, Ymén I. Solid state characterization of pharmaceuticals. John Wiley & Sons; 2011.

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Funding

Isra University (Jordan) provided funding for Gailany Ouda towards his MSc. Najran University and Aston University provided financial support to Hamad Alyami and Affiong Iyrie work in this research, respectively.

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Correspondence to Eman Z. Dahmash.

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Ouda, G.I., Dahmash, E.Z., Alyami, H. et al. A Novel Technique to Improve Drug Loading Capacity of Fast/Extended Release Orally Dissolving Films with Potential for Paediatric and Geriatric Drug Delivery. AAPS PharmSciTech 21, 126 (2020). https://doi.org/10.1208/s12249-020-01665-5

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  • DOI: https://doi.org/10.1208/s12249-020-01665-5

KEY WORDS

  • orally dissolving films
  • drug load
  • fast-release films
  • extended-release films
  • paediatric formulations
  • geriatric formulations