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Formulation, Optimization and Evaluation of Nanoparticulate Oral Fast Dissolving Film Dosage Form of Nitrendipine

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Abstract

The primary objective of the present research work was to develop nanoparticles incorporating (nanoparticulate) fast dissolving (orodispersible) film evincing enhanced solubility and bioavailability of nitrendipine (NIT). An antisolvent sonoprecipitation method was employed to produce the NIT nanosuspension (NS), which was optimized using the 32 optimal response surface design and then the optimized one was evaluated for various parameters (Gandhi et al., AAPS PharmSciTech 22 (1):1–15, 2021). The NIT nanoparticulate orodispersible film (N-ODF) was prepared utilizing the nanosuspension by the solvent casting method using the Vijay film-forming instrument. The N-ODF was optimized by the 23 full factorial design and was evaluated for several parameters. The optimized NS depicted a particle size of 505.74 ± 15.48 nm with a polydispersity index (PDI) of 0.083 ± 0.006 (Fig. 1b). The NIT nanoparticles showed a striking increment in saturation solubility (26.14 times), when compared with plain NIT (2). The developed NIT N-ODF exhibited thickness (0.148 ± 0.008 mm), folding endurance (280.33 ± 5.51 times), surface pH (6.86 ± 0.05), tensile strength (8.25 ± 0.13 kg/cm2), % elongation (63.5 ± 1.97%), and disintegration time (24.60 ± 1.31 s) to be within the standard intended limit. The in vitro dissolution study unveiled 100.28 ± 2.64% and 100.68 ± 2.50% of NIT release from lyophilized nanocrystals (in 8 min) and N-ODF (in 3.5 min), respectively, whereas the conventional NIT tablet took 30 min to release 99.94 ± 1.57% of NIT (Gandhi et al., AAPS PharmSciTech 22 (1):1–15, 2021). The in vivo pharmacokinetic study in rabbits inferred the achievement of significantly (p < 0.05) higher bioavailability of NIT on release from N-ODF in comparison to the conventional NIT tablet. Thus, the generation of N-ODF can be considered as a propitious move toward improving the efficacy of NIT to treat hypertension and angina pectoris.

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References

  1. Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenization. Eur J Pharm Biopharm. 2006;62:3–16. https://doi.org/10.1016/j.ejpb.2005.05.009.

    Article  CAS  PubMed  Google Scholar 

  2. Gandhi NV, Deokate UA, Sachidanand SA. Development of nanonized nitrendipine and its transformation into nanoparticulate oral fast dissolving drug delivery system. AAPS PharmSciTech. 2021;22(3):1–15. https://doi.org/10.1208/s12249-021-01963-6.

    Article  CAS  Google Scholar 

  3. Desai PP, Date AA, Patravale VB. Overcoming poor oral bioavailability using nanoparticle formulations-opportunities and limitations. Drug Discov Today Technol. 2012;9(2):e87–95. https://doi.org/10.1016/j.ddtec.2011.12.001.

    Article  CAS  Google Scholar 

  4. Sharma M, Sharma R, Jain DK. Nanotechnology based approaches for enhancing oral bioavailability of poorly water soluble antihypertensive drugs. Scientifica. 2016;2016:1–11. https://doi.org/10.1155/2016/8525679.

    Article  CAS  Google Scholar 

  5. Majeed A, Raza SN, Khan NA. Hydrotrophy: novel solubility enhancement technique: a review. Int J Pharm Sci Res. 2019;10(3):1025–36. https://doi.org/10.13040/IJPSR.0975-8232.

    Article  CAS  Google Scholar 

  6. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharmaceutics. 2012;2012:1–10. https://doi.org/10.5402/2012/195727.

    Article  CAS  Google Scholar 

  7. Sunder S, Nair R. Methods of nanonization of drugs for enhancing their dissolution. Eur J Advanc Engineer Techno. 2016;3(8):101–10.

    Google Scholar 

  8. Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015;10(1):13–23. https://doi.org/10.1016/j.ajps.2014.08.005.

    Article  Google Scholar 

  9. Pardeike J, Strohmeier DM, Schrödl N, Voura C, Gruber M. Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines. Int J Pharm. 2011;420(1):93–100. https://doi.org/10.1016/j.ijpharm.2011.08.033.

    Article  CAS  PubMed  Google Scholar 

  10. Tripathi KD. Essentials of Medical. Pharmacology. 2003:494–6.

  11. Quan P, Xia D, Piao H, Shi K, Jia Y, Cui F. Nitrendipine nanocrystals: its preparation, characterization, and in vitro-in vivo evaluation. AAPS PharmSciTech. 2011;12(4):1136–43. https://doi.org/10.1208/s12249-011-9682-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xia D, Quan P, Piao H, Sun S, Yin Y, Cui F. Preparation of stable nitrendipine nanosuspensions using the precipitation – ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci. 2010;40(4):325–34. https://doi.org/10.1016/j.ejps.2010.04.006.

    Article  CAS  PubMed  Google Scholar 

  13. Reddy LH, Ghosh B. Fast-dissolving-drug-delivery-systems: a review of the literature. Indian J Pharm Sci. 2002:31–336.

  14. 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;51:193–201. https://doi.org/10.1016/j.bfopcu.2013.05.002.

    Article  Google Scholar 

  15. Karki S, Kim H, Jeong Na S, Shin D, Jo K, Lee J. Thin films as an emerging platform for drug delivery. Asian J Pharm Sci. 2016;11:559–74.

    Article  Google Scholar 

  16. Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharma J. 2015;24:1–10. https://doi.org/10.1016/j.jsps.2015.02.024.

    Article  Google Scholar 

  17. Steiner D, Finke JH, Kwade A. Efficient production of nanoparticle-loaded orodispersible films by process integration in a stirred media mill. Int J Pharm. 2016;511:804–13. https://doi.org/10.1016/j.ijpharm.2016.07.058.

    Article  CAS  PubMed  Google Scholar 

  18. Bajaj A, Rao M, Pardeshi A, Sali D. Nanocrystallization by evaporative antisolvent technique for solubility and bioavailability enhancement of telmisartan. AAPS PharmSciTech. 2012;13(4):1331–40. https://doi.org/10.1208/s12249-012-9860-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jermain SV, Brough C, Williams RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery-an update. Int J Pharm. 2018;535:379–92. https://doi.org/10.1016/j.ijpharm.2017.10.051.

    Article  CAS  PubMed  Google Scholar 

  20. Junghanns JUA, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295–309. https://doi.org/10.2147/ijn.s595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shen B, Shen C, Yuan X, Bai J, Yuan Q, Xu H. Development and characterization of an orodispersible film containing drug nanoparticles. Eur J Pharm Biopharm. 2013;85:1348–56. https://doi.org/10.1016/j.ejpb.2013.09.019.

    Article  CAS  PubMed  Google Scholar 

  22. Gurdale MS, Lade MS, Payghan SA, D'souza JI. Fast dissolving HPMC E5 based oral film for rapid absorption of metoprolol tartrate. Eur J Pharm Med Res. 2014;1(1):75–91.

    Google Scholar 

  23. Lai F, Franceschini I, Corrias F, Sala MC, Cilurzo F, Sinicoa C, et al. Maltodextrin fast dissolving films for quercetin nanocrystal delivery: a feasibility study. Carbohydr Polym. 2015;121:217–23. https://doi.org/10.1016/j.carbpol.2014.11.070.

    Article  CAS  PubMed  Google Scholar 

  24. Sharma R, Kamboj S, Singh G, Rana V. Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance. Financ Res Lett. 2016;84:55–69. https://doi.org/10.1016/j.ejps.2016.01.006.

    Article  CAS  Google Scholar 

  25. Jelvehgari M, Montazam SH, Soltani S, Mohammadi R, Azar K. Fast dissolving oral thin film drug delivery systems consist of ergotamine tartrate and caffeine anhydrous. Pharm Sci. 2015;21(2):102–10. https://doi.org/10.15171/PS.2015.24.

    Article  Google Scholar 

  26. Tran TT, Tran KA, Tran PH. Modulation of particle size and molecular interactions by sonoprecipitation method for enhancing dissolution rate of poorly water-soluble drug. Ultrason-Sonochem. 2015;24:256–63. https://doi.org/10.1016/j.ultsonch.2014.11.020.

    Article  CAS  PubMed  Google Scholar 

  27. Mishra B, Sahoo J, Dixit PK. Fabrication of cinnarizine nanosuspensions by ultrasonication technique: a systematic study of formulation parameters on particle size and in-vitro dissolution. Biopharm J. 2015;1(1):12–21. https://doi.org/10.22159/ijap.2018v10i2.23075.

    Article  CAS  Google Scholar 

  28. Pimparade MB, Maurya AS, Bae J, Morott JT. Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology. Eur J Pharm Biopharm. 2017;119:81–90. https://doi.org/10.1016/j.ejpb.2017.06.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bonsu MA, Ofori-kwakye K, Kipo SL, Boakye-gyasi ME, Fosu M. Development of oral dissolvable films of diclofenac sodium for osteoarthritis using albizia and khaya gums as hydrophilic film formers. J Drug Deliv. 2016;2016:1–11. https://doi.org/10.1155/2016/6459280.

    Article  CAS  Google Scholar 

  30. Patil P, Shrivastava SK. Formulation, evaluation and optimization of fast dissolving oral film of selective antihypertensive drug. World J Pharm Pharm Sci. 2014;3(8):996–1060.

    CAS  Google Scholar 

  31. Pawar SV, Junagade MS. Formulation and evaluation of mouth dissolving film of risperidone. Int J PharmTech Res. 2015;8(6):218–30.

    CAS  Google Scholar 

  32. Patel R, Shah D. Nanoparticles loaded sublingual film as an effective treatment of chemotherapy induced nausea and vomiting. Int J PharmTech Res. 2015;8(10):77–87.

    CAS  Google Scholar 

  33. Mahboob MBH, Riaz T, Jamshaid M, Bashir I, Zulfiqar S. Oral films: a comprehensive review. Int Curr Pharmaceu J. 2016;5(12):111–7 http://www.icpjonline.com/documents/Vol5Issue12/03.pdf.

    Article  CAS  Google Scholar 

  34. Singh CK, Tiwari V, Shankar R, Mishra CP, Jain S, Jaiswal S. A short review on oral fast dissolving film containing cefpodoxime proxetil nanoparticle. World J Pharm Pharm Sci. 2016;5(1):1549–77.

    CAS  Google Scholar 

  35. Bharti K, Mittal P, Mishra B. Formulation and characterization of fast dissolving oral films containing buspirone hydrochloride nanoparticles using design of experiment. J Drug Deliv Sci and Tech. 2019;49:420–32. https://doi.org/10.1016/j.jddst.2018.12.013.

    Article  CAS  Google Scholar 

  36. Chonkar AD, Rao JV, Managuli RS, Mutalik S, Dengale S, Jain P, et al. Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation. Eur J Pharm Biopharm. 2016;103:179–91. https://doi.org/10.1016/j.ejpb.2016.04.001.

    Article  CAS  PubMed  Google Scholar 

  37. Reddy PS, Murthy KVR. Formulation and evaluation of oral fast dissolving films of poorly soluble drug ezetimibe using transcutol Hp. Indian J of Pharma Edu and Res. 2018;52(3):398–407. https://doi.org/10.5530/ijper.52.3.46.

    Article  CAS  Google Scholar 

  38. Venkateswarlu K. Preparation and evaluation of fast dissolving buccal thin films of bufotenin. J In Silico In Vitro Pharmacol. 2016;2(4):2–6.

    Google Scholar 

  39. ElMeshad AN, Hagrasy ASE. Characterization and optimization of orodispersible mosapride film formulations. AAPS PharmSciTech. 2011;12(4):1384–92. https://doi.org/10.1208/s12249-011-9713-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Elbary AA, Ali AA, Aboud HM. Enhanced dissolution of meloxicam from orodispersible tablets prepared by different methods. Bull Fac Pharmac. 2012;50(2):89–97. https://doi.org/10.1016/j.bfopcu.2012.07.001.

    Article  CAS  Google Scholar 

  41. Chavan DU, Marques SM, Bhide PJ, Kumar L, Shirodkar RK. Rapidly dissolving Felodipine nanoparticle strips - formulation using design of experiment and characterization. J Drug Deliv Sci and Tech. 2020;60:1–15. https://doi.org/10.1016/j.jddst.2020.102053.

    Article  CAS  Google Scholar 

  42. Vijayanand P, Patil JS, Reddy MV. Formulation and comparative pharmacokinetic evaluation of orodispersible tablets and films of nebivolol hydrochloride. J Pharm Inves. 2015;45:237–47.

    Article  CAS  Google Scholar 

  43. El-setouhy DA, El-malak NSA. Formulation of a novel tianeptine sodium orodispersible film. AAPS PharmSciTech. 2010;11(3):1018–25. https://doi.org/10.1208/s12249-010-9464-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Papadimitriou S, Bikiaris D. Novel self-assembled core–shell nanoparticles based on crystalline amorphous moieties of aliphatic copolyesters for efficient controlled drug release. J Control Release. 2009;138:177–84. https://doi.org/10.1016/j.jconrel.2009.05.013.

    Article  CAS  PubMed  Google Scholar 

  45. Chatwal GR, Anand SK. Instrumental methods of chemical analysis. New Delhi: Himalaya Publishing House. p. 2.60–71.

  46. Chauhan A, Chauhan P. Powder XRD technique and its applications in science and technology. J Anal Bioanal Tech. 2014;5(5):1–5. https://doi.org/10.4172/2155-9872.1000212.

    Article  CAS  Google Scholar 

  47. Bala R, Pawar P, Khanna S, Arora S. Orally dissolving strips: a new approach to oral drug delivery system. Int J Pharm Investig. 2013;3(2):67–76. https://doi.org/10.4103/2230-973X.114897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Winarti L, Ameliana L, Nurahmanto D. Formula optimization of orally disintegrating tablet containing meloxicam nanoparticles. Indonesian J Pharm. 2017;28(1):53–64. https://doi.org/10.14499/indonesianjpharm28iss1pp53.

    Article  CAS  Google Scholar 

  49. Desai PM, Liew CV, Heng PWS. Review of disintegrants and the disintegration phenomena. J Pharm Sci. 2016;105(9):2545–55. https://doi.org/10.1016/j.xphs.2015.12.019.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge Government College of Pharmacy, Aurangabad (M.S.), India; Wockhardt Ltd., Aurangabad (M.S.), India; and M.E.S.’s College of Pharmacy, Ahmednagar (M.S.), India, for the resource support provided.

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Authors and Affiliations

  1. Department of Pharmaceutics, Government College of Pharmacy, Dr. Babasaheb Ambedkar Marathwada University, 431005 (M.S), Aurangabad, India

    Neha Vishal Gandhi & Uday Arvind Deokate

  2. Yash Institute of Pharmacy, Dr. Babasaheb Ambedkar Marathwada University, 431134 (M.S.), Aurangabad, India

    Sachidanand Shankar Angadi

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  1. Neha Vishal Gandhi
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Contributions

Neha Vishal Gandhi: conceptualization, methodology, investigation, software, formal analysis, data curation, writing—original draft, writing—review and editing, final approval of the version of the manuscript to be published, and agreement to be accountable for all aspects of the work. Uday Arvind Deokate: resources, writing—review and editing, final approval of the version of the manuscript to be published, and agreement to be accountable for all aspects of the work. Sachidanand Shankar Angadi: resources, writing—review and editing, final approval of the version of the manuscript to be published, and agreement to be accountable for all aspects of the work.

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Gandhi, N.V., Deokate, U.A. & Angadi, S.S. Formulation, Optimization and Evaluation of Nanoparticulate Oral Fast Dissolving Film Dosage Form of Nitrendipine. AAPS PharmSciTech 22, 218 (2021). https://doi.org/10.1208/s12249-021-02100-z

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