Formulation and characterization of bilastine - cyclodextrin inclusion complex loaded as an oral fast dissolving film

Abstract

Oral fast dissolving films (OFDFs) are the most innovative oral solid pharmaceutical dosage form, especially for elderly and pediatric patients who may have dysphagia. Bilastine (BLA), is a second – generation antihistamine used to manage allergy symptoms; it is very slightly soluble in water. The main objective of this research was to enhance the solubility and dissolution rate of BLA by complexation technique. Ternary complex of BLA: methyl β- cyclodextrin (M-β-CD): soluplus® 5% w/w was prepared via solvent evaporation technique as a trial to enhance its solubility to be prepared as OFDF by incorporated into aqueous polymeric solution. Seven formulas of OFDFs were prepared using the solvent casting method using Polyvinyl alcohol, Hydroxy propyl methyl cellulose E5, and Pullulan as polymers that form film, PEG 400, and glycerin as plasticizers. The prepared films were estimated for their physical, and mechanical properties, drug content, and dissolution rate. The results showed that,the prepared complex enhanced the solubility of the BLA in water (11 times more than the pure BLA in distilled water) and it was easily utilized for the preparation of the OFDFs. The PVA-based formulation in the presence of glycerin as a plasticizer (F4), showed a homogenous clear film with accepted folding endurance (300), the shortest disintegration time (16.66 seconds), and complete release within five minutes. In conclusion, complexation of BLA with M-β CD was an efficient method for enhancing its solubility and dissolution rate to be easily prepared as OFDF with acceptable physical properties.

Keywords

• Bilastine
• Cyclodextrin-complex
• Methyl-β-cyclodextrin
• oral fast- dissolving films
• ternary complex

References

1. [1] Rajab NA, Hussein AA. Formulation and in-vitro evaluation of darifenacin hydrobromide as buccal films. Iraqi J Pharm Sci. 2019; 28 (2):83-94. https://doi.org/10.31351/vol28iss2pp83-94
2. [2] Ali HMS, Al-khedairy EBH. Formulation and in vitro evaluation of taste-masked prednisolone orodispersible tablets. J Fac Med Baghdad. 2023; 65(3) : 192-198. https://doi.org/10.32007/jfacmedbagdad.2057
3. [3] Saeed AM, Alaayedi M, Al-Jarsha HY. Effect of natural / synthetic polymers and super disintegrants on the formulation of zafirlukast fast dissolving film. Res J Pharm Technol. 2022; 15(4): 1567-1572. http://dx.doi.org/10.52711/0974-360X.2022.00261
4. [4] Arpa MD, Unukur MZ, Erim UC. Formulation, characterization and in vitro release studies of terbinafine hydrochloride loaded buccal films. J Res Pharm. 2021; 25(5): 667-680. https://dx.doi.org/10.29228/jrp.58
5. [5] Abbas IK, Al hammid SNA. Preparation and characterization of bilastine solid self-nanoemulsion using liquisolid technique. Al-Rafidian J Med Sci. 2023; 5:78-85. https://doi.org/10.54133/ajms.v5i.160
6. [6] Nechipadappu SK, Swain D. Combined synthetic and solubility aspects of orotate salt of bilastine. J Mol Struct. 2023; 1271: 134148. https://doi.org/10.1016/j.molstruc.2022.134148
7. [7] Jain H , Chella N. Methods to improve the solubility of therapeutical natural products : a review. Environ Chem Lett. 2021; 19 (1) :111-121. http://dx.doi.org/10.1007/s10311-020-01082-x
8. [8] Hadi BM, Al-khedairy EBH . Preparation and characterization of atorvastatine calcium trihydrate – cyclodextrin inclusion complex. Int J Drug Deliv Technol. 2022; 12 (3) : 1171-1179. http://dx.doi.org/10.25258/ijddt.12.3.41

9. [9] Muankaew C, Loftsson T. Cyclodextrin-based formulations: A non-ınvasive platform for targeted drug delivery. Basic Clin Pharmacol Toxicol. 2018;122(1):46-55. https://doi.org/10.1111/bcpt.12917
10. [10] Mane PT, Wakure BS, Wakte PS. Ternary inclusion complex of docetaxel using β- cyclodextrin and hydrophilic polymer : physicochemical characterization and in-vitro anticancer activity. J Appl Pharm Sci. 2022; 12 (12) : 150 161. http://dx.doi.org/10.7324/JAPS.2022.121216
11. [11] Sri SJ, Bhikshapathi DVRN. Development and optimization of fast dissolving oral film containing aripiprazole. Int J Pharm Sci Drug Res. 2017; 9(6): 327-333. https://doi.org/10.25004/IJPSDR.2017.090607
12. [12] Chen Q, Martin R, Hoag SW, Wood RA, Mao HQ, Keet C. Formulation and characterization of orally dissolving thin films containing the German cockroach Blatella germanica (Bla g 2) Allergen. Int J Pharma Sci. 2014;4(5):730-735.
13. [13] Sajayan K, Swathy kk, Chandran S, Jafna MC, Nair RS, Sourav K, Kappally S, Sreejith KR, Joseph J. Development and evaluation of fast dissolving oral films of mefenamic acid for the management of fever. Ind J Pharm Edu Res. 2023; 57 (1):s41-s51. https://doi.org/10.5530/ijper.57.1s.6
14. [14] Salehi S, Boddohi S. New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Prog Biomater. 2017; 6: 175-187. https://doi.org/10.1007/s40204-017-0077-7
15. [15] Chandrika KM, Kumar TP, Raju PN. Formulation and evaluation of amlodipine besylate orally disintegrating films. Pharma Innov. 2014; 3 (1): 23-32.
16. [16] 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): 408-417.
17. [17] Dharmasthala S, Shabaraya AR, Andrade GS, Shriram RG, Hebbar S, Dubey A. Fast dissolving oral film of piroxicam: solubility enhancement by forming an inclusion complex with β-cyclodextrin, formulation and evaluation. J Young Pharm. 2019; 11(1) : 1-6. http://dx.doi.org/10.5530/jyp.2019.11.1
18. [18] Mahaparale S, Wagh BS. Formulation and evaluation of mouth dissolving film of glycopyrolate. Int J Creat Res Thoughts. 2021; 9(9): 509-516.
19. [19] Salman ZD, Maraie NK, Al-abbassi MG, Ghareeb MM. In vitro / in vivo evaluation and bioavailability study of amitriptyline hydrochloride from the optimized oral fast dissolving films. UK J Pharm Biosci. 2014; 2(6) : 32-42. http://dx.doi.org/10.20510/ukjpb/2/i6/91171
20. [20] Jaafar IS. Formulation and in vitro evaluation of fast dissolving film of metoclopramide hydrochloride. Int J Chemtech Res . 2017; 10(4) : 26-38.
21. [21] Hussain HAM, Al-khedairy EBH. Preparation and in vitro evaluation of cyclodextrin based effervescent and dispersible granules of carbamazepine. Int J App Pharm. 2018; 10 (6) : 290-297. http://dx.doi.org/10.22159/ijap.2018v10i6.28276
22. [22] Hosny KM, El-say KM, Ahmed OA. Optimized sildenafil citrate fast orodissolvable film : A promising formula for overcoming the barriers hindering erectile dysfunction treatment. Drug Deliv. 2016; 23(1): 355-361. https://doi.org/10.3109/10717544.2014.916763
23. [23] Abed-Al-hammid SN, Saleeh HH. Formulation and evaluation of flurbiprofen oral film. Iraqi J Pharm Sci. 2014; 23 (1) : 53-59. https://doi.org/10.31351/vol23iss1pp53-59
24. [24] Khalil YI. Preparation and characterization of montelukast sodium (SMLT) as a dual sustained release buccal strips. Iraqi J Pharm Sci. 2015; 24(2) : 61-71. https://doi.org/10.31351/vol24iss2pp61-71
25. [25] Radhi ZA, Ghareeb MM. Preparation and evaluation of extended release ocular inserts of rebamipide for local effect using casting technique. Iraqi J Pharm Sci. 2019; 28(1): 24-36. http://dx.doi.org/10.31351/vol28iss1pp24-36
26. [26] Tamer MA, Al-hammid SNA, Ahmed B. Formulation and in vitro evaluation of bromocriptine mesylate as fast dissolving oral film. Int J App Pharm. 2018; 10 (1) : 7-20. https://doi.org/10.22159/ijap.2018v10i1.22615
27. [27] 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%2F2230-973X.114897
28. [28] Patil SS, Patil SJ, Vakhariya RR, Chopade AR, Mohite SK. Formulation and evaluation of fast dissolving buccal film of curcumin as promising route of buccal delivery. J Univ Shanghai Sci Technol. 2021; 23(5) : 498-505. https://doi.org/10.51201/JUSST/21/05157
29. [29] Bhattacharyya S, Rangarao BG. Formulation development of oral disintegrating film of fexofenadine hydrochloride. Acta Pharm Sci. 2022; 60(4) : 345-362. https://doi.org/ 10.23893/1307-2080.APS6023.
30. [30] Diaz DA, Colgan ST, Langer CS, Bandi NT, Likar MD, Van Alstine L. Dissolution similarity requirements: How similar or dissimilar are the global https://doi.org/10.1208%2Fs12248-015-9830-9 regulatory expectations? AAPS J. 2016;18(1):15-22.