Formulation and Characterization of Clozapine Nanosuspension as a Sublingual Film
DOI:
https://doi.org/10.54133/ajms.v6i2.772Keywords:
Bioavailability, Clozapine, Nanosuspension, Sublingual filmAbstract
Background: Clozapine (CLZ) is a potent antipsychotic drug that suppresses the symptoms of schizophrenia and mania. Clozapine falls into Class II (BCS); its poor bioavailability is attributed to low water solubility and an extensive first-pass effect. Objective: To prepare CLZ as a nanosuspension (NS) to improve its low water solubility and load it into a sublingual film to enhance oral bioavailability. Methods: CLZ nanosuspensions are prepared by the “solvent anti-solvent precipitation” method using Soluplus as a stabilizing agent. We evaluated the polydispersity index (PDI) and the particle size of the CLZ nanosuspension formulations. The optimized formula of CLZ nanosuspension is loaded directly onto a sublingual thin film, eliminating the need for freeze-drying for solidification by the solvent casting approach. The sublingual films were characterized by thickness, surface pH, folding endurance, disintegration time, and in vitro dissolution rate. Results: We selected the formula F1 sublingual film as the best, as it demonstrated a uniform thickness of 0.087mm, good flexibility, and a surface pH of 6.7. It disintegrated quickly in 13 seconds and had a faster in vitro dissolution rate (3 min) compared to the CLZ ordinary films. Conclusions: The results confirmed the success of CLZ NS as a sublingual thin film for dissolution rate enhancement, which may improve oral bioavailability.
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Zeng F, Wang L, Zhang W, Shi K, Zong L. Formulation and in vivo evaluation of orally disintegrating tablets of clozapine/hydroxypropyl-β-cyclodextrin inclusion complexes. AAPS PharmSciTech. 2013;14(2):854–860. doi: 10.1208/s12249-013-9973-x.
Agrawal MB, Patel MM. Design, development and in vivo evaluation of clozapine loaded adhesive diffusion controlled system for the treatment of schizophrenia. J Drug Deliv Sci Technol. 2021;64:102629. doi: 10.1016/j.jddst.2021.102629.
Hua S. Advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. Front Pharmacol. 2019;10. doi: 10.3389/fphar.2019.01328.
Li J, Pan H, Ye Q, Shi C, Zhang X, Pan W. Carvedilol-loaded polyvinylpyrrolidone electrospun nanofiber film for sublingual delivery. J Drug Deliv Sci Technol. 2020;58. doi: 10.1016/j.jddst.2020.101726.
Song Q, Shen C, Shen B, Lian W, Liu X, Dai B, et al. Development of a fast dissolving sublingual film containing meloxicam nanocrystals for enhanced dissolution and earlier absorption. J Drug Deliv Sci Technol. 2018;43:243–252. doi1: 0.1016/j.jddst.2017.10.020.
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):1392–1400. doi: 10.1208/s12249-018-0954-y.
Lakshmi P, Kumar GA. Nanosuspension technology: a review. Int J Pharm Pharm Sci. 2010;2(SUPPL. 4):35–40.
Alzalzalee RA, Kassab HJ. Factors affecting the preparation of cilnidipine nanoparticles. Iraqi J Pharm Sci. 2023;32:235–243. doi: 10.31351/vol32issSuppl.pp235-243.
Toma NM, Abdulrasool AA. Formulation and evaluation of montelukast sodium nanoparticles for transdermal delivery. Int J Drug Deliv Technol. 2021;11(2):530–538. doi: 10.25258/ijddt.11.2.52.
Abdal-hammid SN. Formulation and in vitro evaluation of bromocriptine mesylate formulation and in vitro evaluation of bromocriptine mesylate as fast dissolving oral film. Int J Appl Pharm. 10(1):7–20. doi: 10.22159/ijap.2018v10i1.22615.
Kadhim ZJ, Rajab NA. Formulation and characterization of glibenclamide nanoparticles as an oral film. J Drug Devel Technol. 2022;12(1):387. doi: 10.25258/ijddt.12.1.70.
Khalil YI. Preparation and characterization of montelukast sodium (SMLT) as a dual sustained release buccal strips. Iraqi J Pharm Sci. 2015;24(2). doi: 10.31351/vol24iss2pp61-71.
Abbas IK, Rajab NA, Hussein AA. Formulation and in-vitro evaluation of darifenacin hydrobromide as buccal films. Iraqi J Pharm Sci. 2019;28(2):83–94. doi: 10.31351/vol28iss2pp83-94.
Elshafeey AH, El-Dahmy RM. Formulation and development of oral fast-dissolving films loaded with nanosuspension to augment paroxetine bioavailability: In vitro characterization, ex vivo permeation, and pharmacokinetic evaluation in healthy human volunteers. Pharmaceutics. 2021;13(11). doi: 10.3390/pharmaceutics13111869.
Abd-Alhammid SN, Saleeh HH. Formulation and evaluation of flurbiprofen oral film. Iraqi J Pharm Sci. 2014;23(1):53–59. doi: 10.31351/vol23iss1pp53-59.
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. doi: 10.31351/vol28iss1pp24-36.
Alzalzaly RAA, Kassab H. Cilnidipine nanoparticles oral film: preparation and evaluation cilnidipine nanoparticles oral film: preparation and evaluation. J Res Pharmacy. 2024. doi: 10.29228/jrp.687
Rajab NA, Jassim ZE, Hameed AM. Preparation and characterization of lacidipine as an oral fast dissolving film. J Pharm Res. 2018;12(3):321-326.
Zayed GM, Rasoul SA El, Ibrahim MA, Saddik MS, Alshora DH. In vitro and in vivo characterization of domperidone-loaded fast dissolving buccal films. Saudi Pharm J. 2020;28(3):266–273. doi: 10.1016/j.jsps.2020.01.005.
Zaman M, Hassan R, Razzaq S, Mahmood A, Amjad MW, Raja MAG, et al. Fabrication of polyvinyl alcohol based fast dissolving oral strips of sumatriptan succinate and metoclopramide HCL. Sci Prog. 2020;103(4):1–21. doi: 10.1177/0036850420964302.
Panthi VK, Jha SK, Pangeni R, Paudel KR. Formulation and development of adapalene topical nanohydrogel using different surfactants and cosurfactants for antiacne activity: in vitro and ex vivo evaluation. J Nanomater. 2022;2022. doi: 10.1155/2022/6889293.
Alwan RM, Rajab NA. Nanosuspensions of selexipag: formulation, characterization, and in vitro evaluation. Iraqi J Pharm Sci. 2021;30(1):144–153. doi: 10.31351/vol30iss1pp144-153.
Dora CP, Singh SK, Kumar S, Datusalia AK, Deep A. Development and characterization of nanoparticles of glibenclamide by solvent displacement method. Acta Pol Pharm Drug Res. 2010;67(3):283–290.
Apriani EF, Septina S, Ahmadi A. Effect of stirring speed and stirring time on characterization of clindamycin HCl ethosomal and Ich Q1a (R2) stability test. Farmacia. 2023;71(5):956–965. doi: 10.31925/farmacia.2023.5.10.
Gera S, Talluri S, Rangaraj N, Sampathi S. Formulation and evaluation of naringenin nanosuspensions for bioavailability enhancement. AAPS PharmSciTech. 2017;18(8):3151–3162. doi: 10.1208/s12249-017-0790-5.
Rani KC, Parfati N, Aryani NLD, Winantari AN, Fitriani EW, Pradana AT, et al. Development, evaluation, and molecular docking of oral dissolving film of atenolol. Pharmaceutics. 2021;13(10):1–17. doi: 10.3390/pharmaceutics13101727.
Chen O, Martin R, Hoag SW, Wood RA, Mao HQ. HHS public access formulation and characterization of orally dissolving thin films containing the German cockroach Blatella germanica (Bla g 2) allergen. Physiol Behav. 2017;176(3):139–148.
Jassim ZE, Mohammed MF, Sadeq ZA. Formulation and evaluation of fast dissolving film of lornoxicam. Asian J Pharm Clin Res. 2018;11(9):217–223. doi: 10.22159/ajpcr.2018.v11i9.27098.
Sri SJ, Krishna KSM, Kusuma D, Shankar CU. Formulation and in-vitro evaluation of benazepril mouth dissolving films. Indo Am J Pharm Sci. 2018;5(1):552–560. doi: 10.5281/zenodo.1162756.
Pathare YS, Hastak VS, Bajaj AN. Polymers used for fast disintegrating oral films: A review. Int J Pharm Sci Rev Res. 2013;21(1):169–178.
Kulkarni AS, Deokule HA, Mane MS, Ghadge DM. Exploration of different polymers for use in the formulation of oral fast dissolving strips. J Curr Pharm Res. 2010;2(1):33–35.
Pan YS, Xiong DS, Ma RY. Preparation and swelling behavior of polyvinyl alcohol physiological saline gel. J Cent South Univ Technol. 2006;13(1):27–31. doi: 10.1007/s11771-006-0101-x.
Pradhan R, Budhathoki U, Thapa P. Formulation of once a day controlled release tablet of indomethacin based on HPMC-mannitol. Kathmandu Univ J Sci Eng Technol. 1970;4(1):55–67. doi: 10.3126/kuset.v4i1.2884.
Bharkatiya M, Nema RK, Bhatnagar M. Designing and characterization of drug free patches for transdermal application. Int J Pharm Sci Drug Res. 2010;2(1):35.
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