Design and physico-mechanical evaluation of fast-dissolving valsartan polymeric drug delivery system by electrospinning method

Document Type : Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Objective(s): Chronic hypertension is a pervasive morbidity and the leading risk factor for cardiovascular diseases. Valsartan, as an antihypertensive drug, has low solubility and bioavailability. The application of orodispersible films of valsartan is suggested to improve its bioavailability. With this dosage form, the drug dissolves rapidly in saliva and is absorbed readily without the need for water. 
Materials and Methods: For this purpose, valsartan with polyvinylpyrrolidone (PVPK90) polymer were exposed to the electrospinning technique to construct orodispersible nanofilms. The optimum obtained nanofiber, selected by Design-Expert software, was evaluated in terms of mechanical strength for evaluation of the flexibility and fragility of the nanofibers. The drug content, wettability, and disintegration tests, as well as the release assessment of the nanofibers, were performed followed by DSC, FTIR, and XRD assays.
Results: The uniform nanofibers’ diameter increased with the increase of the polymer concentration. The tensile test verified a stress reduction at the yield point as the polymer concentration increased. Then, the 492 nm nanofiber with above 90% drug encapsulation, containing 8% polymer and 18% valsartan made below 9 kV, was selected. The wetting time was less than 30 sec and over 90% of the drug was released in less than 2 min. The XRD and DSC studies also confirmed higher valsartan solubility due to the construction alternations in nanofibers. The FTIR examination indicated the chemical bonding between the drug and the polymer.
Conclusion: The selected nanofibers of valsartan present the essential drug feature and acceptable drug release for further investigations.

Keywords

References

1. Ladak N, Thompson J. Drugs acting on the heart: antihypertensive drugs. Anaesth Intensive Care Med 2009; 10:392–395. 
2. Mahmud A, Feely J. Low-dose quadruple antihypertensive combination: more efficacious than individual agents-a preliminary report. Hypertension 2007; 49:272–275. 
3. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol 2020; 16:223–37. 
4. Dina R, Jafari M. Angiotensin II-receptor antagonists: an overview. Am J Heal Pharm 2000; 57:1231–1241. 
5. Kannan K, Krishna R, Manikandan M, Selvamuthukumar S, Manavalan R. Development and evaluation of valsartan film coated tablets. J Pharm Sci Res 2012; 4:1866. 
6. Varghese NJ, Ramanarayanan V, Chandrashekar Janakiram JJ. Assessment of quality of prescription writing among dental and medical students and practitioners in Kerala. J Nat Sci Biol Med 2018; 9:27-33. 
7. Sweetman SC, others. Martindale: the complete drug reference. Vol. 3709. Pharmaceutical Press London; 2009. 
8. Siddiqui N, Husain A, Chaudhry L, Alam MS, Mitra M, Bhasin PS. Pharmacological and pharmaceutical profile of valsartan: A review. J Appl Pharm Sci 2011; 1:12–19. 
9. Saydam M, Takka S. Bioavailability file: valsartan. FABAD J Pharm Sci 2007; 32:185-196. 
10. Grahame DG, others. Oxford textbook of clinical pharmacology and drug therapy. 1992; 3rd ed., 2002: 256-258.
11. Rajinikanth PS, Suyu Y, Garg S. Development and in vitro characterization of self-nanoemulsifying drug delivery systems of valsartan. Int J Pharmacol Pharm Sci 2012; 6:733–873. 
12. Yan Y-D, Sung JH, Kim KK, Kim DW, Kim JO, Lee B-J, et al. Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes. Int J Pharm 2012; 422:202–210. 
13. Kumar KV, Arunkumar N, Verma PRP, Rani C, others. Preparation and in vitro characterization of Valsartan solid dispersions using skimmed milk powder as carrier. Int J PharmTech Res 2009; 1:431–437. 
14. Muthu MS, Singh S. Studies on biodegradable polymeric nanoparticles of risperidone: in vitro and in vivo evaluation. 2008; 3: 305-3019.
15. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12:413–420. 
16. Visser JC, Woerdenbag HJ, Hanff LM, Frijlink HW. Personalized medicine in pediatrics: the clinical potential of orodispersible films. Aaps pharmscitech 2017; 18:267–272. 
17. Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique. AAPs PharmSciTech 2004; 5:10–5. 
18. Habib W, Khankari R, Hontz J. Fast-dissolve drug delivery systems. Crit Rev Ther Drug Carr Syst 2000; 17. 
19. Krampe R, Visser JC, Frijlink HW, Breitkreutz J, Woerdenbag HJ, Preis M. Oromucosal film preparations: points to consider for patient centricity and manufacturing processes. Expert Opin Drug Deliv 2016; 13:493–506. 
20. Musazzi UM, Khalid GM, Selmin F, Minghetti P, Cilurzo F. Trends in the production methods of orodispersible films. Int J Pharm 2020; 576:118963. 
21. 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; 24:537–546. 
22. Desu PK, Brahmaiah B, Nagalakshmi A, Neelima K, Nama S, Baburao C. An overview on rapid dissolving films. Asian J Pharm Res 2013; 3:15–23. 
23. Chachlioutaki K, Tzimtzimis EK, Tzetzis D, Chang M-W, Ahmad Z, Karavasili C, et al. Electrospun orodispersible films of isoniazid for pediatric tuberculosis treatment. Pharmaceutics 2020; 12:1-14.
24. Sjöholm E, Sandler N. Additive manufacturing of personalized orodispersible warfarin films. Int J Pharm 2019; 564:117–123. 
25. Ibrahim HK, El-Setouhy DA. Valsartan orodispersible tablets: formulation, in vitro/in vivo characterization. Aaps Pharmscitech 2010; 11:189–196. 
26. Chang R-K, Guo X, Burnside BA, Couch RA. Fast-dissolving tablets. Pharm Technol 2000; 24:52-58. 
27. Qin Z, Jia X-W, Liu Q, Kong B, Wang H. Fast dissolving oral films for drug delivery prepared from chitosan/pullulan electrospinning nanofibers. Int J Biol Macromol 2019; 137:224–231. 
28. Lee Y, Kim K, Kim M, Choi DH, Jeong SH. Orally disintegrating films focusing on formulation, manufacturing process, and characterization. J Pharm Investig 2017; 47:183–201. 
29. Park H-M, Lee W-K, Park C-Y, Cho W-J, Ha C-S. Environmentally friendly polymer hybrids Part I Mechanical, thermal, and barrier properties of thermoplastic starch/clay nanocomposites. J Mater Sci 2003; 38:909–915. 
30. Lim CT, others. Nanofiber technology: current status and emerging developments. Prog Polym Sci 2017; 70:1–17. 
31. Mali KK, J Dias RJ, Ghorpade VS, Havaldar VD. Taste masked oral fast dissolving sublingual strips of rizatriptan benzoate for migraine therapy. 2017;21:235-242.
32. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control release 2009; 139:94–107. 
33. Song G, Lin Y, Zhu Z, Zheng H, Qiao J, He C, et al. Strong Fluorescence of Poly (N-vinylpyrrolidone) and Its Oxidized Hydrolyzate. Macromol Rapid Commun 2015; 36:278–285. 
34. Dave RH. Overview of pharmaceutical excipients used in tablets and capsules. Drug Top Oct 2008; 24:1–13. 
35. Park JH, Lee HW, Chae DK, Oh W, Yun JD, Deng Y, et al. Electrospinning and characterization of poly (vinyl alcohol)/chitosan oligosaccharide/clay nanocomposite nanofibers in aqueous solutions. Colloid Polym Sci 2009; 287:943–950. 
36. Wang Z, Crandall C, Sahadevan R, Menkhaus TJ, Fong H. Microfiltration performance of electrospun nanofiber membranes with varied fiber diameters and different membrane porosities and thicknesses. Polymer (Guildf) 2017; 114:64–72. 
37. Ji HM, Lee HW, Karim MR, Cheong IW, Bae EA, Kim TH, et al. Electrospinning and characterization of medium-molecular-weight poly (vinyl alcohol)/high-molecular-weight poly (vinyl alcohol)/montmorillonite nanofibers. Colloid Polym Sci 2009; 287:751–758. 
38. Charernsriwilaiwat N, Opanasopit P, Rojanarata T, Ngawhirunpat T, Supaphol P. Preparation and characterization of chitosan-hydroxybenzotriazole/polyvinyl alcohol blend nanofibers by the electrospinning technique. Carbohydr Polym 2010; 81:675–680. 
39. Park JH, Karim MR, Kim IK, Cheong IW, Kim JW, Bae DG, et al. Electrospinning fabrication and characterization of poly (vinyl alcohol)/montmorillonite/silver hybrid nanofibers for antibacterial applications. Colloid Polym Sci 2010; 288:115–121. 
40. Sapountzi E, Braiek M, Chateaux J-F, Jaffrezic-Renault N, Lagarde F. Recent advances in electrospun nanofiber interfaces for biosensing devices. Sensors 2017; 17:1-29. 
41. Garg K, Bowlin GL. Electrospinning jets and nanofibrous structures. Biomicrofluidics 2011; 5:13403. 
42. Drosou C, Krokida M, Biliaderis CG. Composite pullulan-whey protein nanofibers made by electrospinning: Impact of process parameters on fiber morphology and physical properties. Food Hydrocoll 2018; 77:726–375. 
43. Torres-Giner S, Gimenez E, Lagaron JM. Characterization of the morphology and thermal properties of zein prolamine nanostructures obtained by electrospinning. Food Hydrocoll 2008; 22:601–614. 
44. Sattar M, Alshawi MA, Mosa MN. Formulation and in vitro Evaluation of Valsartan Flash Tablet. Syst Rev Pharm 2020; 11:213–219. 
45. AnjiReddy K, Karpagam S. Chitosan nanofilm and electrospun nanofiber for quick drug release in the treatment of Alzheimer’s disease: In vitro and in vivo evaluation. Int J Biol Macromol 2017; 105:131–142. 
46. Mazumder S, Pavurala N, Manda P, Xu X, Cruz CN, Krishnaiah YSR. Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films. Int J Pharm 2017; 527:151–160. 
47. D’Souza S. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm 2014; 2014:1-12. 
48. Gupta MS, Kumar TP. Characterization of orodispersible films: an overview of methods and introduction to a new disintegration test apparatus using LDR-LED sensors. J Pharm Sci 2020; 109: 2925-2942.
49. Brenner EK, Schiffman JD, Thompson EA, Toth LJ, Schauer CL. Electrospinning of hyaluronic acid nanofibers from aqueous ammonium solutions. Carbohydr Polym 2012; 87:926–929. 
50. Zhang Q, Li M, Liu J, Long S, Yang J, Wang X. Porous ultrafine fibers via a salt-induced electrospinning method. Colloid Polym Sci 2012; 290:793–799. 
51. Mirtič J, Balažic H, Zupančič Š, Kristl J. Effect of solution composition variables on electrospun alginate nanofibers: Response surface analysis. Polymers (Basel) 2019; 11:692. 
52. Lai KL, Fang Y, Han H, Li Q, Zhang S, Li HY, et al. Orally-dissolving film for sublingual and buccal delivery of ropinirole. Colloids Surfaces B Biointerfaces 2018; 163:9–18. 
53. Reda RI, Wen MM, El-Kamel AH. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis. Int J Nanomedicine 2017; 12:2335–2351. 
54. Steiner D, Finke JH, Kwade A. Model-based description of disintegration time and dissolution rate of nanoparticle-loaded orodispersible films. Eur J Pharm Sci 2019; 132:18–26. 
55.     Yousaf AM, Malik UR, Shahzad Y, Mahmood T, Hussain T. Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization. J Pharm Anal 2019; 9:34–39. 
56. Singh SK, Vuddanda PR, Singh S, Srivastava AK. A comparison between use of spray and freeze drying techniques for preparation of solid self-microemulsifying formulation of valsartan and in vitro and in vivo evaluation. Biomed Res Int 2013; 2013:1-13.
57. Skotnicki M, Gaweł A, Cebe P, Pyda M. Thermal behavior and phase identification of Valsartan by standard and temperature-modulated differential scanning calorimetry. Drug Dev Ind Pharm 2013; 39:1508–1514. 
58. Abedinoghli D, Charkhpour M, Osouli-Bostanabad K, Selselehjonban S, Emami S, Barzegar-Jalali M, et al. Electrosprayed nanosystems of carbamazepine--PVP K30 for enhancing its pharmacologic effects. Iran J Pharm Res 2018; 17:1431-1443.
59. Thakkar S, Misra M. Electrospun polymeric nanofibers: New horizons in drug delivery. Eur J Pharm Sci 2017; 107:148–167. 
60. Mahapatra AK, Murthy PN, Biswal S, Mahapatra APK, Pradhan SP. Dissolution Enhancement and Physicochemical Characterization of Valsartan in Solid Dispersions with CD, HP-CD, and PVP K-30. Dissolution Technol 2011; 18:39–45. 
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 12
December 2021
Pages 1683-1694

Files

Share

How to cite

Statistics