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AAPS PharmSciTech

, Volume 19, Issue 5, pp 2203–2212 | Cite as

Formulation, Characterization, and Optimization of Captopril Fast-Dissolving Oral Films

  • Fatemeh Rezaee
  • Fariba Ganji
Research Article

Abstract

This work aimed to using optimization study to formulate a patient-friendly captopril fast-dissolving oral film with satisfactory disintegration time. Films were made with pullulan and hydroxypropyl methyl cellulose (HPMC) by using the solvent-casting method. Cellulose nanofiber (CNF) was used as a compatibilizer and glycerine was used as a plasticizer. In order to find an optimum formulation, a response surface methodology and a central composite design were employed. The concentration percentages of pullulan and glycerine were considered to be the design factors. Disintegration time, tensile strength, percent elongation at break, and folding endurance were considered to be the responses. The results showed that CNF improved the compatibility and tensile strength of the pullulan and HPMC blend. Also, the rigid nature of CNF reduced the film elongation but the addition of glycerine improved its flexibility. All formulations showed an acceptable uniformity content and dissolution rate. Complete dissolution for all formulations occurred within 2 min. Films with 26% pullulan, 74% HPMC, 1% CNF, and 5% glycerine were reported to be optimum formulations for captopril fast-dissolving oral films, with 95% confidence levels. The in vivo comparison of optimized formulation with a conventional captopril sublingual tablet exhibited significant increase in AUC (~ 62%) and Cmax (~ 52%) and a major decrease in Tmax (~ 33%). The overall results showed that the captopril FDF is a promising candidate for enhanced in vivo orotransmucosal absorption.

KEY WORDS

oral film captopril optimization cellulose nanofiber compatibilizer 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    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.CrossRefPubMedGoogle Scholar
  2. 2.
    Patel VF, Liu F, Brown MB. Advances in oral transmucosal drug delivery. J Control Release. 2011;153:106–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Chen L, Daoxiao CH, Xinhui ZH, Hong S, Yindi K, Rongyue ZH, et al. Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation. AAPS PharmSciTech. 2017;18(8):2957–64.CrossRefGoogle Scholar
  4. 4.
    Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control Release. 2009;139:94–107.CrossRefPubMedGoogle Scholar
  5. 5.
    Colonna C, Genta I, Perugini P, Pavanetto F, Modena T, Valli M, et al. 5-methyl-pyrrolidinone chitosan films as carriers for buccal administration of proteins. AAPS PharmSciTech. 2006;7(3):E107–13.CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Juliano C, Cossu M, Pigozzi P, Rassu G, Giunchedi P. Preparation, in vitro characterization and preliminary in vivo evaluation of buccal polymeric films containing chlorhexidine. AAPS PharmSciTech. 2008;9(4):1153–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Preis M. Orally disintegrating films and mini-tablets—innovative dosage forms of choice for pediatric use. AAPS PharmSciTech. 2015;16(2):234–41.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Khan S, Boateng JS, Mitchell J, Trivedi V. Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole. AAPS PharmSciTech. 2015;16(4):800–10.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Prajapati VD, Jani GK, Khanda SM. Pullulan: an exopolysaccharide and its various applications. Carbohydr Polym. 2013;95(1):540–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Singh RS, Saini GK, Kennedy JF. Pullulan: microbial sources, production and applications. Carbohydr Polym. 2008;73(4):515–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Huang S, O’Donnell KP, Keen JM, Rickard MA, McGinity JW, Williams IIIRO. A new extrudable form of hypromellose: AFFINISOL™ HPMC HME. AAPS PharmSciTech. 2016;17(1):106–19.CrossRefPubMedGoogle Scholar
  12. 12.
    Abdelbary A, Bendas ER, Ramadan AA, Mostafa DA. Pharmaceutical and pharmacokinetic evaluation of a novel fast dissolving film formulation of flupentixol dihydrochloride. AAPS Pharm Sci Tech. 2014;15(6):1603–10.CrossRefGoogle Scholar
  13. 13.
    Nishimura M, Matsuura K, Tsukioka T, Yamashita H, Inagaki N, Sugiyama T, et al. In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm. 2009;368(1–2):98–102.CrossRefPubMedGoogle Scholar
  14. 14.
    Senta-Loys Z, Bourgeois S, Pailler-Mattei C, Agusti G, Briançon S, Fessi H. Formulation of orodispersible films for paediatric therapy: investigation of feasibility and stability for tetrabenazine as drug model. J Pharm Pharm. 2017;69(5):582–92.CrossRefGoogle Scholar
  15. 15.
    Sievens-Figueroa L, Bhakay A, Jerez-Rozo JI, Pandya N, Romañach RJ, Michniak-Kohn B, et al. Preparation and characterization of hydroxypropyl methyl cellulose films containing stable BCS class II drug nanoparticles for pharmaceutical applications. Int J Pharm. 2012;423(2):496–508.CrossRefPubMedGoogle Scholar
  16. 16.
    Alletto M, Burgio A, Fulco G, Paradiso R, Piangiamore M, Vancheri F. Sublingual captopril in hypertensive crises. Recenti Prog Med. 1992;83(9):503–5.PubMedGoogle Scholar
  17. 17.
    Castillo AC, Rodriguez M, Gonzalez E, Rodriguez F, Estruch J. Dose-response effect of sublingual captopril in hypertensive crises. J Clin Pharmacol. 1988;28(7):667–70.CrossRefGoogle Scholar
  18. 18.
    Franceschini I, Selmin F, Pagani S, Minghetti P, Cilurzo F. Nanofiller for the mechanical reinforcement of maltodextrins orodispersible films. Carbohydr Polym. 2016;136(1):676–81.CrossRefPubMedGoogle Scholar
  19. 19.
    Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharm J. 2016;24:537–46.CrossRefPubMedGoogle Scholar
  20. 20.
    Jankowski A, Skorek A, Krzyśko K, Zarzycki PK, Ochocka RJ, Lamparczyk H. Captopril: determination in blood and pharmacokinetics after single oral dose. J Pharm Biomed Anal. 1995;13(4–5):655–60.CrossRefPubMedGoogle Scholar
  21. 21.
    Araújo AAS, Bezerra MDS, Storpirtis S, Matos JDR. Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC. Braz J Pharm Sci. 2010;46(1):37–43.CrossRefGoogle Scholar
  22. 22.
    Thomas S, Grohens Y, Jyotishkumar P. Characterization of polymer blends: miscibility, morphology and interfaces. Weinheim: John Wiley & Sons; 2014.  https://doi.org/10.1002/9783527645602.
  23. 23.
    Pereda M, Dufresne A, Aranguren MI, Marcovich NE. Polyelectrolyte films based on chitosan/olive oil and reinforced with cellulose nanocrystals. Carbohydr Polym. 2014;101(1):1018–26.CrossRefPubMedGoogle Scholar
  24. 24.
    Cano A, Fortunati E, Cháfer M, González-Martínez C, Chiralt A, Kenny J. Effect of cellulose nanocrystals on the properties of pea starch–poly (vinyl alcohol) blend films. J Mater Sci. 2015;50(21):6979–92.CrossRefGoogle Scholar
  25. 25.
    Chen CC, White JL. Compatibilizing agents in polymer blends: interfacial tension, phase morphology, and mechanical properties. Polym Eng Sci. 1993;33(14):923–30.CrossRefGoogle Scholar
  26. 26.
    Kulkarni A, Deokule H, Mane M, Ghadge D. Exploration of different polymers for use in the formulation of oral fast dissolving strips. Int J Curr Pharm Res. 2010;2(1):33–5.Google Scholar
  27. 27.
    Benet LZ, Bhatia V, Singh P, Guillory JK, Sokoloski TD. Effect of inert tablet ingredients on drug absorption I. Effect of polyethylene glycol 4000 on the intestinal absorption of four barbiturates. J Pharm Sci. 1966;55(1):63–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Chaudhary H, Gauri S, Rathee P, Kumar V. Development and optimization of fast dissolving oro-dispersible films of granisetron HCl using Box–Behnken statistical design. Bull Fac Pharm Cairo Univ. 2013;51(2):193–201.CrossRefGoogle Scholar
  29. 29.
    Liew KB, Tan YTF, Peh KK. Effect of polymer, plasticizer and filler on orally disintegrating film. Drug Dev Ind Pharm. 2014;40(1):110–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Selmin F, Franceschini I, Cupone IE, Minghetti P, Cilurzo F. Aminoacids as non-traditional plasticizers of maltodextrins fast-dissolving films. Carbohydr Polym. 2015;115(1):613–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Arrieta M, Fortunati E, Dominici F, Rayón E, López J, Kenny JM. PLA-PHB/cellulose based films: mechanical, barrier and disintegration properties. Polym Degrad Stab. 2014;107(1):139–49.CrossRefGoogle Scholar
  32. 32.
    Preis M, Knop K, Breitkreutz J. Mechanical strength test for orodispersible and buccal films. Int J Pharm. 2014;461(1):22–9.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Faculty of Chemical EngineeringTarbiat Modares UniversityTehranIran

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