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Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Dexamethasone Acetate Nanocrystals, Characterization and Dissolution Studies in Presence of Polymorphic Phases

Author(s): Flavia Lemos Ayres da Gama Bastos, Thúlio Wliandon Lemos Barbosa*, Bruna Lallo da Silva, João Augusto Oshiro Junior and Leila Aparecida Chiavacci

Volume 11, Issue 4, 2023

Published on: 11 May, 2023

Page: [373 - 382] Pages: 10

DOI: 10.2174/2211738511666230328134440

Price: $65

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Abstract

Background: A drug with poor water-solubility, like Dexamethasone acetate, can present lower bioavailability conventional for pharmaceutical formulations, and the presence of polymorphs in the raw material can lead to drug quality problems.

Objective: In this study, nanocrystals of dexamethasone acetate were synthesized by high pressure homogenizer (HPH) method in surfactant poloxamer 188 (P188) solid dispersion and the bioavailable in raw material with polymorphism presence was evaluated.

Methods: The powder pre-suspension was prepared by the HPH process, and the nanoparticles formed were incorporated in P188 solutions. The nanocrystals formed were characterized by techniques of XRD, SEM, FTIR, thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), dynamic light scattering (DLS) to analyze the particle size and zeta potential, and in vitro evaluation by dissolution studies.

Results: The characterization techniques were adequate to show the presence of raw material with physical moisture between two dexamethasone acetate polymorphs. The nanocrystals formed in the presence of the P188 in the formulation showed a considerable increase in the rate of dissolution of the drug in the medium and in the size of the stable nanocrystals, even in the presence of dexamethasone acetate polymorphs.

Conclusion: The results showed that it was possible to produce dexamethasone nanocrystals by HPH process with regular size by the presence of the small amount of P188 surfactant. This article presents a novelty in the development of dexamethasone nanoparticles that have different polymorphic forms in their physical composition.

Graphical Abstract

[1]
da Silva FLO, Marques MBDF, Kato KC, Carneiro G. Nanonization techniques to overcome poor water-solubility with drugs. Expert Opin Drug Discov 2020; 15(7): 853-64.
[http://dx.doi.org/10.1080/17460441.2020.1750591]
[2]
Zhang M, Qin X, Zhao Z, et al. A self-amplifying nanodrug to manipulate the Janus-faced nature of ferroptosis for tumor therapy. Nanoscale Horiz 2022; 7(2): 198-210.
[http://dx.doi.org/10.1039/D1NH00506E] [PMID: 35023537]
[3]
Zhou S, Shang Q, Wang N, Li Q, Song A, Luan Y. Rational design of a minimalist nanoplatform to maximize immunotherapeutic efficacy: Four birds with one stone. J Control Release 2020; 328: 617-30.
[http://dx.doi.org/10.1016/j.jconrel.2020.09.035] [PMID: 32976902]
[4]
Lu Y, Li Y, Wu W. Injected nanocrystals for targeted drug delivery. Acta Pharm Sin B 2016; 6(2): 106-13.
[http://dx.doi.org/10.1016/j.apsb.2015.11.005] [PMID: 27006893]
[5]
Gao L, Liu G, Ma J, Wang X, Zhou L, Li X. Drug nanocrystals: In vivo performances. J Control Release 2012; 160(3): 418-30.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.013] [PMID: 22465393]
[6]
Keck C, Müller R. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm 2006; 62(1): 3-16.
[http://dx.doi.org/10.1016/j.ejpb.2005.05.009] [PMID: 16129588]
[7]
Zhai X, Lademann J, Keck CM, Müller RH. Nanocrystals of medium soluble actives—Novel concept for improved dermal delivery and production strategy. Int J Pharm 2014; 470(1-2): 141-50.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.060] [PMID: 24813782]
[8]
Colombo M, Staufenbiel S, Rühl E, Bodmeier R. In situ determination of the saturation solubility of nanocrystals of poorly soluble drugs for dermal application. Int J Pharm 2017; 521(1-2): 156-66.
[http://dx.doi.org/10.1016/j.ijpharm.2017.02.030] [PMID: 28223247]
[9]
Mirza RM, Ahirrao SP, Kshirsagar SJ. A nanocrystal technology: To enhance solubility of poorly water soluble drugs. J Appl Pharm Sci 2017; 5: 01-13.
[10]
Gigliobianco MR, Casadidio C, Censi R, di Martino P. Nanocrystals of poorly soluble drugs: Drug bioavailability and physicochemical stability. Pharmaceutics 2018; 10: 134.
[http://dx.doi.org/10.3390/pharmaceutics10030134]
[11]
Saini JK, Kumar S, Kaur J. Development of nanocrystal formulation with improved dissolution. J Drug Deliv Ther 2018; 8(5): 118-29.
[http://dx.doi.org/10.22270/jddt.v8i5.1946]
[12]
Chogale MM, Ghodake VN, Patravale VB. Performance parameters and characterizations of nanocrystals: A brief review. Pharmaceutics 2016; 8: 26.
[http://dx.doi.org/10.3390/pharmaceutics8030026]
[13]
Kumar R, Thakur AK, Chaudhari P, Banerjee N. Particle size reduction techniques of pharmaceutical compounds for the enhancement of their dissolution rate and bioavailability. J Pharm Innov 2021; 17: 333-52.
[http://dx.doi.org/10.1007/s12247-020-09530-5]
[14]
Günday Türeli N, Türeli AE. Industrial perspectives and future of oral drug delivery. In: Nanotechnology for oral drug delivery: From concept to applications. 2020; pp. 483-502.
[http://dx.doi.org/10.1016/B978-0-12-818038-9.00016-8]
[15]
Bertoni S, Passerini N, Albertini B. Nanomaterials for oral drug administration.In: Nanotechnology for Oral Drug Delivery: From Concept to Applications. 2020; pp. 27-76.
[http://dx.doi.org/10.1016/B978-0-12-818038-9.00004-1]
[16]
Raghava Srivalli KM, Mishra B. Drug nanocrystals: A way toward scale-up. Saudi Pharm J 2016; 24(4): 386-404.
[http://dx.doi.org/10.1016/j.jsps.2014.04.007] [PMID: 27330370]
[17]
Sun W, Tian W, Zhang Y, He J, Mao S, Fang L. Effect of novel stabilizers-Cationic polymers on the particle size and physical stability of poorly soluble drug nanocrystals. Nanomedicine 2012; 8(4): 460-7.
[http://dx.doi.org/10.1016/j.nano.2011.07.006] [PMID: 21839057]
[18]
Tuomela A, Hirvonen J, Peltonen L. Stabilizing agents for drug nanocrystals: Effect on bioavailability. Pharmaceutics 2016; 8: 16.
[http://dx.doi.org/10.3390/pharmaceutics8020016]
[19]
Peltonen L, Strachan C, Rades T, Grohganz H, Löbmann K. Understanding critical quality attributes for nanocrystals from preparation to delivery. Molecules 2015; 20: 22286-300.
[http://dx.doi.org/10.3390/molecules201219851]
[20]
Rocha ED, Ferreira MRS, dos Santos Neto E, et al. Enhanced in vitro antimicrobial activity of polymyxin B-Coated nanostructured lipid carrier containing dexamethasone acetate. J Pharm Innov 2021; 16(1): 125-35.
[http://dx.doi.org/10.1007/s12247-020-09427-3]
[21]
Terzis A, Theophanides T. The crystal and molecular structure of 9[alpha]-fluoro-16[alpha]-methyl-11[beta],17,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-acetate monohydrate. Acta Crystallogr Sect B 1975; 31: 796-801.
[http://dx.doi.org/10.1107/S0567740875003822]
[22]
Silva RP, Ambrósio MFS, Piovesan LA, et al. New polymorph form of dexamethasone acetate. J Pharm Sci 2018; 107(2): 672-81.
[http://dx.doi.org/10.1016/j.xphs.2017.10.001] [PMID: 29031975]
[23]
Bonfilio R, Souza MCO, Leal JS, Viana OMMS, Doriguetto AC, Araújo MB. Solubility and dissolution studies of tibolone polymorphs. Braz J Pharm Sci 2018; 53(4): 233.
[http://dx.doi.org/10.1590/s2175-97902017000400233]
[24]
Vasconcelos T, Prezotti F, Araújo F, et al. Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int J Pharm 2021; 595: 120245.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120245] [PMID: 33484925]
[25]
Kassem M, Abdelrahman A, Ghorab M, Ahmed M, Khalil R. Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 2007; 340(1-2): 126-33.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.011] [PMID: 17600645]
[26]
Oliveira PFM, Willart JF, Siepmann J, Siepmann F, Descamps M. Using milling to explore physical states: The amorphous and polymorphic forms of dexamethasone. Cryst Growth Des 2018; 18(3): 1748-57.
[http://dx.doi.org/10.1021/acs.cgd.7b01664]
[27]
Passerini N, Albertini B, González-Rodríguez ML, Cavallari C, Rodriguez L. Preparation and characterisation of ibuprofen–poloxamer 188 granules obtained by melt granulation. Eur J Pharm Sci 2002; 15(1): 71-8.
[http://dx.doi.org/10.1016/S0928-0987(01)00210-X] [PMID: 11803133]
[28]
Shi X, Ding Z, Bao J, Wang C. Preparation and in vitro/vivo evaluation of new celecoxib solid dispersions with co-carrier containing aerosil and poloxamer 188. Pharm Chem J 2021; 54(10): 1033-9.
[http://dx.doi.org/10.1007/s11094-021-02316-0]
[29]
Youshia J, Ali ME, Lamprecht A. Artificial neural network based particle size prediction of polymeric nanoparticles. Eur J Pharm Biopharm 2017; 119: 333-42.
[http://dx.doi.org/10.1016/j.ejpb.2017.06.030] [PMID: 28694160]
[30]
Berbel Manaia E, Paiva Abuçafy M, Chiari-Andréo BG, Lallo Silva B, Oshiro-Júnior JA, Chiavacci L. Physicochemical characterization of drug nanocarriers. Int J Nanomedicine 2017; 12: 4991-5011.
[http://dx.doi.org/10.2147/IJN.S133832] [PMID: 28761340]
[31]
Delage S, Couvrat N, Sanselme M, Cartigny Y, Coquerel G. Stability of solid phases in the dexamathasone acetate/water system. MATEC Web of Conferences 2013 3: 01036.
[http://dx.doi.org/10.1051/matecconf/20130301036]
[32]
Schnitzler E, Carvalho-Filho MAS, Stadler CC, Volpato AM, Ionashiro M. Application of differential scanning calorimetry (dsc) in the thermal characterization of dexamethasone acetate, excipients and dexamethasone cream. Eclét Quím 2001; 26(0): 41-52.
[http://dx.doi.org/10.1590/S0100-46702001000100003]
[33]
El-Kamel A, El-Habashy S, Allam A. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: Formulation and in vitro/in vivo evaluation. Int J Nanomedicine 2016; 11: 2369-80.
[http://dx.doi.org/10.2147/IJN.S93354] [PMID: 27307735]
[34]
Li Y, Zhao X, Zu Y, Zhang Y. Preparation and characterization of paclitaxel nanosuspension using novel emulsification method by combining high speed homogenizer and high pressure homogenization. Int J Pharm 2015; 490(1-2): 324-33.
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.070] [PMID: 26027492]
[35]
Shoormeij Z, Taheri A, Homayouni A. Preparation and physicochemical characterization of meloxicam orally fast disintegration tablet using its solid dispersion. Braz J Pharm Sci 2018; 53(4): 176.
[http://dx.doi.org/10.1590/s2175-97902017000400176]
[36]
Mura P, Gratteri P, Faucci MT. Compatibility studies of multicomponent tablet formulations: DSC and experimental mixture design. J Therm Anal Calorim 2002; 68(2): 541-51.
[http://dx.doi.org/10.1023/A:1016048021064]
[37]
Barzegar-Jalali M, Alaei-Beirami M, Javadzadeh Y, et al. Comparison of physicochemical characteristics and drug release of diclofenac sodium–eudragit® RS100 nanoparticles and solid dispersions. Powder Technol 2012; 219: 211-6.
[http://dx.doi.org/10.1016/j.powtec.2011.12.046]
[38]
Jain S, Datta M. Oral extended release of dexamethasone: Montmorillonite–PLGA nanocomposites as a delivery vehicle. Appl Clay Sci 2015; 104: 182-8.
[http://dx.doi.org/10.1016/j.clay.2014.11.028]
[39]
Nanaki S, Eleftheriou RM, Barmpalexis P, Kostoglou M, Karavas E, Bikiaris D. Aprepitant drug in ternary pharmaceutical solid dispersions with Soluplus® and poloxamer 188 prepared by melt mixing. Sci 2019; 1(1): 29.
[http://dx.doi.org/10.3390/sci1010029]
[40]
Fischer SM, Brandl M, Fricker G. Effect of the non-ionic surfactant Poloxamer 188 on passive permeability of poorly soluble drugs across Caco-2 cell monolayers. Eur J Pharm Biopharm 2011; 79(2): 416-22.
[http://dx.doi.org/10.1016/j.ejpb.2011.04.010] [PMID: 21549839]

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