Effects of pharmaceutical excipients on drug supersaturation in amorphous solid dispersions

WANG Huijian; WANG Yanfei; SU Wei; FU Qiang

doi:10.11665/j.issn.1000-5048.2023123001

Journal of China Pharmaceutical University > 2024 > 55(6): 725-733. > DOI: 10.11665/j.issn.1000-5048.2023123001

WANG Huijian, WANG Yanfei, SU Wei, et al. Effects of pharmaceutical excipients on drug supersaturation in amorphous solid dispersions[J]. J China Pharm Univ, 2024, 55(6): 725 − 733. DOI: 10.11665/j.issn.1000-5048.2023123001

Citation:

PDF (993 KB)

Effects of pharmaceutical excipients on drug supersaturation in amorphous solid dispersions

WANG Huijian¹,
WANG Yanfei¹,
SU Wei¹,
FU Qiang^{1, 2, ,}

1.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016
2.
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China

Funds: This work was supported by the Liaoning Provincial Revitalization Talents Program (XLYC2203044); the Key Research Projects of Liaoning Provincial Department of Education (JYTZD2023142) and the Outstanding Youth Lifting Cultivation Program of Shenyang Pharmaceutical University (YQ202113)

More Information

Received Date: December 29, 2023

Graphical Abstract

Abstract

Abstract

Using the amorphous solid dispersion (ASD) technology, poorly water-soluble drugs can be formulated into high-energy amorphous forms. After oral administration, a kinetic supersaturated solution is formed in the gastrointestinal tract, and oral bioavailability is thus effectively improved. As important components of ASDs, pharmaceutical excipients affect the supersaturation of ASDs. Therefore, it is significant to clarify the effects of various types of pharmaceutical excipients on the supersaturated solutions for the development of ASDs. This paper reviews the effects of polymers, small-molecule excipients, and porous materials on the supersaturated solutions formed after dissoptlution of ASD with an emphasis on the mechanisms of various types of pharmaceutical excipients on the supersaturated solutions, providing theoretical guidance for the rational selection of medicinal excipients in the development of ASDs.
- pharmaceutical excipients,
- amorphous solid dispersion,
- drug supersaturated solution

FullText(HTML)

References (67)

References

[1]	Kalepu S, Nekkanti V. Insoluble drug delivery strategies: review of recent advances and business prospects[J]. Acta Pharm Sin B, 2015, 5(5): 442-453. doi: 10.1016/j.apsb.2015.07.003
[2]	Sverdlov Arzi R, Sosnik A. Electrohydrodynamic atomization and spray-drying for the production of pure drug nanocrystals and co-crystals[J]. Adv Drug Deliv Rev, 2018, 131: 79-100. doi: 10.1016/j.addr.2018.07.012
[3]	Qiao N, Li MZ, Schlindwein W, et al. Pharmaceutical cocrystals: an overview[J]. Int J Pharm, 2011, 419(1/2): 1-11.
[4]	Trubitsyn G, Nguyen VN, di Tommaso C, et al. Impact of covalently Nile Red and covalently Rhodamine labeled fluorescent polymer micelles for the improved imaging of the respective drug delivery system[J]. Eur J Pharm Biopharm, 2019, 142: 480-487. doi: 10.1016/j.ejpb.2019.07.020
[5]	Bazzo GC, Pezzini BR, Stulzer HK. Eutectic mixtures as an approach to enhance solubility, dissolution rate and oral bioavailability of poorly water-soluble drugs[J]. Int J Pharm, 2020, 588: 119741. doi: 10.1016/j.ijpharm.2020.119741
[6]	Shi Q, Li F, Yeh S, et al. Physical stability of amorphous pharmaceutical solids: nucleation, crystal growth, phase separation and effects of the polymers[J]. Int J Pharm, 2020, 590: 119925. doi: 10.1016/j.ijpharm.2020.119925
[7]	Bhujbal SV, Mitra B, Jain U, et al. Pharmaceutical amorphous solid dispersion: a review of manufacturing strategies[J]. Acta Pharm Sin B, 2021, 11(8): 2505-2536. doi: 10.1016/j.apsb.2021.05.014
[8]	Thi TD, van Speybroeck M, Barillaro V, et al. Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS[J]. Eur J Pharm Sci, 2009, 38(5): 479-488. doi: 10.1016/j.ejps.2009.09.012
[9]	Zhao ZJ, Higashi K, Ueda K, et al. Revealing the mechanism of morphological variation of amorphous drug nanoparticles formed by aqueous dispersion of ternary solid dispersion[J]. Int J Pharm, 2021, 607: 120984. doi: 10.1016/j.ijpharm.2021.120984
[10]	Budiman A, Citraloka ZG, Muchtaridi M, et al. Inhibition of crystal nucleation and growth in aqueous drug solutions: impact of different polymers on the supersaturation profiles of amorphous drugs-the case of alpha-mangostin[J]. Pharmaceutics, 2022, 14(11): 2386. doi: 10.3390/pharmaceutics14112386
[11]	Gao P, Guyton ME, Huang TH, et al. Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations[J]. Drug Dev Ind Pharm, 2004, 30(2): 221-229. doi: 10.1081/DDC-120028718
[12]	Zhang W, Hate SS, Russell DJ, et al. Impact of surfactant and surfactant-polymer interaction on desupersaturation of clotrimazole[J]. J Pharm Sci, 2019, 108(10): 3262-3271. doi: 10.1016/j.xphs.2019.05.035
[13]	Rahman M, Coelho A, Tarabokija J, et al. Synergistic and antagonistic effects of various amphiphilic polymer combinations in enhancing griseofulvin release from ternary amorphous solid dispersions[J]. Eur J Pharm Sci, 2020, 150: 105354. doi: 10.1016/j.ejps.2020.105354
[14]	Budiman A, Nurani NV, Laelasari E, et al. Effect of drug-polymer interaction in amorphous solid dispersion on the physical stability and dissolution of drugs: the case of alpha-mangostin[J]. Polymers, 2023, 15(14): 3034. doi: 10.3390/polym15143034
[15]	He Y, Liu HF, Bian WQ, et al. Molecular interactions for the curcumin-polymer complex with enhanced anti-inflammatory effects[J]. Pharmaceutics, 2019, 11(9): 442. doi: 10.3390/pharmaceutics11090442
[16]	Yu JY, Kim JA, Joung HJ, et al. Preparation and characterization of curcumin solid dispersion using HPMC[J]. J Food Sci, 2020, 85(11): 3866-3873. doi: 10.1111/1750-3841.15489
[17]	Li J, Fan N, Li C, et al. The tracking of interfacial interaction of amorphous solid dispersions formed by water-soluble polymer and nitrendipine[J]. Appl Surf Sci, 2017, 420: 136-144. doi: 10.1016/j.apsusc.2017.05.123
[18]	Guzmán ML, Manzo RH, Olivera ME. Eudragit E100 as a drug carrier: the remarkable affinity of phosphate ester for dimethylamine[J]. Mol Pharm, 2012, 9(9): 2424-2433. doi: 10.1021/mp300282f
[19]	Yu DY, Li JH, Wang HX, et al. Role of polymers in the physical and chemical stability of amorphous solid dispersion: a case study of carbamazepine[J]. Eur J Pharm Sci, 2022, 169: 106086. doi: 10.1016/j.ejps.2021.106086
[20]	Thakral S, Thakral NK, Majumdar DK. Eudragit: a technology evaluation[J]. Expert Opin Drug Deliv, 2013, 10(1): 131-149. doi: 10.1517/17425247.2013.736962
[21]	Saboo S, Bapat P, Moseson DE, et al. Exploring the role of surfactants in enhancing drug release from amorphous solid dispersions at higher drug loadings[J]. Pharmaceutics, 2021, 13(5): 735. doi: 10.3390/pharmaceutics13050735
[22]	França MT, Nicolay Pereira R, Klüppel Riekes M, et al. Investigation of novel supersaturating drug delivery systems of chlorthalidone: the use of polymer-surfactant complex as an effective carrier in solid dispersions[J]. Eur J Pharm Sci, 2018, 111: 142-152. doi: 10.1016/j.ejps.2017.09.043
[23]	Fung MH, Suryanarayanan R. Effect of organic acids on molecular mobility, physical stability, and dissolution of ternary ketoconazole spray-dried dispersions[J]. Mol Pharm, 2019, 16(1): 41-48. doi: 10.1021/acs.molpharmaceut.8b00593
[24]	Fung MH, DeVault M, Kuwata KT, et al. Drug-excipient interactions: effect on molecular mobility and physical stability of ketoconazole-organic acid coamorphous systems[J]. Mol Pharm, 2018, 15(3): 1052-1061. doi: 10.1021/acs.molpharmaceut.7b00932
[25]	Fung M, Be Rziņš KR, Suryanarayanan R. Physical stability and dissolution behavior of ketoconazole-organic acid coamorphous systems[J]. Mol Pharm, 2018, 15(5): 1862-1869. doi: 10.1021/acs.molpharmaceut.8b00035
[26]	Almotairy A, Almutairi M, Althobaiti A, et al. Effect of pH modifiers on the solubility, dissolution rate, and stability of telmisartan solid dispersions produced by hot-melt extrusion technology[J]. J Drug Deliv Sci Technol, 2021, 65: 102674. doi: 10.1016/j.jddst.2021.102674
[27]	Semjonov K, Salm M, Lipiäinen T, et al. Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions[J]. Int J Pharm, 2018, 541(1/2): 188-197.
[28]	Thenmozhi K, Yoo YJ. Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems[J]. Drug Dev Ind Pharm, 2017, 43(9): 1501-1509. doi: 10.1080/03639045.2017.1321658
[29]	Cai CF, Liu MH, Li Y, et al. A silica-supported solid dispersion of bifendate using supercritical carbon dioxide method with enhanced dissolution rate and oral bioavailability[J]. Drug Dev Ind Pharm, 2016, 42(3): 412-417. doi: 10.3109/03639045.2015.1071833
[30]	Takeuchi H, Nagira S, Yamamoto H, et al. Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method[J]. Int J Pharm, 2005, 293(1/2): 155-164.
[31]	Planinšek O, Kovačič B, Vrečer F. Carvedilol dissolution improvement by preparation of solid dispersions with porous silica[J]. Int J Pharm, 2011, 406(1/2): 41-48.
[32]	Yan HM, Jia XB, Zhang ZH, et al. Study on porous starch as solid dispersion carrier of total Epimedium flavonoids[J]. China J Chin Mater Med (中国中药杂志), 2015, 40(9): 1723-1726.
[33]	Lucio D, Zornoza A, Martínez-Ohárriz MC. Role of microstructure in drug release from chitosan amorphous solid dispersions[J]. Int J Mol Sci, 2022, 23(23): 15367. doi: 10.3390/ijms232315367
[34]	Fujimoto Y, Hirai N, Takatani-Nakase T, et al. Preparation and evaluation of solid dispersion tablets by a simple and manufacturable wet granulation method using porous calcium silicate[J]. Chem Pharm Bull, 2016, 64(4): 311-318. doi: 10.1248/cpb.c15-00838
[35]	Milović M, Simović S, Lošić D, et al. Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier[J]. Eur J Pharm Sci, 2014, 63: 226-232. doi: 10.1016/j.ejps.2014.07.010
[36]	Zhang W, Noland R, Chin S, et al. Impact of polymer type, ASD loading and polymer-drug ratio on ASD tablet disintegration and drug release[J]. Int J Pharm, 2021, 592: 120087. doi: 10.1016/j.ijpharm.2020.120087
[37]	Takano R, Maurer R, Jacob L, et al. Formulating amorphous solid dispersions: impact of inorganic salts on drug release from tablets containing itraconazole-HPMC extrudate[J]. Mol Pharm, 2020, 17(8): 2768-2778. doi: 10.1021/acs.molpharmaceut.9b01109
[38]	Goddeeris C, Willems T, van den Mooter G. Formulation of fast disintegrating tablets of ternary solid dispersions consisting of TPGS 1000 and HPMC 2910 or PVPVA 64 to improve the dissolution of the anti-HIV drug UC 781[J]. Eur J Pharm Sci, 2008, 34(4/5): 293-302.
[39]	Xi HM, Ren J, Novak JM, et al. The effect of inorganic salt on disintegration of tablets with high loading of amorphous solid dispersion containing copovidone[J]. Pharm Res, 2020, 37(4): 70. doi: 10.1007/s11095-020-2772-7
[40]	Koranne S, Lalge R, Suryanarayanan R. Modulation of microenvironmental acidity: a strategy to mitigate salt disproportionation in drug product environment[J]. Mol Pharm, 2020, 17(4): 1324-1334. doi: 10.1021/acs.molpharmaceut.0c00024
[41]	Nie HC, Xu W, Ren J, et al. Impact of metallic stearates on disproportionation of hydrochloride salts of weak bases in solid-state formulations[J]. Mol Pharm, 2016, 13(10): 3541-3552. doi: 10.1021/acs.molpharmaceut.6b00630
[42]	Démuth B, Galata DL, Szabó E, et al. Investigation of deteriorated dissolution of amorphous itraconazole: description of incompatibility with magnesium stearate and possible solutions[J]. Mol Pharm, 2017, 14(11): 3927-3934. doi: 10.1021/acs.molpharmaceut.7b00629
[43]	Li JH, Wang YH, Yu DY. Effects of additives on the physical stability and dissolution of polymeric amorphous solid dispersions: a review[J]. AAPS PharmSciTech, 2023, 24(7): 175. doi: 10.1208/s12249-023-02622-8
[44]	Miller DA, DiNunzio JC, Yang W, et al. Enhanced in vivo absorption of itraconazole via stabilization of supersaturation following acidic-to-neutral pH transition[J]. Drug Dev Ind Pharm, 2008, 34(8): 890-902. doi: 10.1080/03639040801929273
[45]	Ueda K, Higashi K, Yamamoto K, et al. Equilibrium state at supersaturated drug concentration achieved by hydroxypropyl methylcellulose acetate succinate: molecular characterization using (1)H NMR technique[J]. Mol Pharm, 2015, 12(4): 1096-1104. doi: 10.1021/mp500588x
[46]	Hanada M, Jermain SV, Thompson SA, et al. Ternary amorphous solid dispersions containing a high-viscosity polymer and mesoporous silica enhance dissolution performance[J]. Mol Pharm, 2021, 18(1): 198-213. doi: 10.1021/acs.molpharmaceut.0c00811
[47]	Kallakunta VR, Sarabu S, Bandari S, et al. Stable amorphous solid dispersions of fenofibrate using hot melt extrusion technology: effect of formulation and process parameters for a low glass transition temperature drug[J]. J Drug Deliv Sci Technol, 2020, 58: 101395. doi: 10.1016/j.jddst.2019.101395
[48]	Kawakami K, Usui T, Hattori M. Understanding the glass-forming ability of active pharmaceutical ingredients for designing supersaturating dosage forms[J]. J Pharm Sci, 2012, 101(9): 3239-3248. doi: 10.1002/jps.23166
[49]	Xie T, Taylor LS. Dissolution performance of high drug loading celecoxib amorphous solid dispersions formulated with polymer combinations[J]. Pharm Res, 2016, 33(3): 739-750. doi: 10.1007/s11095-015-1823-y
[50]	Li N, Mosquera-Giraldo LI, Borca CH, et al. A comparison of the crystallization inhibition properties of bile salts[J]. Cryst Growth Des, 2016, 16(12): 7286-7300. doi: 10.1021/acs.cgd.6b01470
[51]	Chen J, Ormes JD, Higgins JD, et al. Impact of surfactants on the crystallization of aqueous suspensions of celecoxib amorphous solid dispersion spray dried particles[J]. Mol Pharm, 2015, 12(2): 533-541. doi: 10.1021/mp5006245
[52]	Harmon P, Galipeau K, Xu W, et al. Mechanism of dissolution-induced nanoparticle formation from a copovidone-based amorphous solid dispersion[J]. Mol Pharm, 2016, 13(5): 1467-1481. doi: 10.1021/acs.molpharmaceut.5b00863
[53]	Schram CJ, Taylor LS, Beaudoin SP. Influence of polymers on the crystal growth rate of felodipine: correlating adsorbed polymer surface coverage to solution crystal growth inhibition[J]. Langmuir, 2015, 31(41): 11279-11287. doi: 10.1021/acs.langmuir.5b02486
[54]	Zhang S, Britten JF, Chow AHL, et al. Impact of crystal structure and polymer excipients on the melt crystallization kinetics of itraconazole polymorphs[J]. Cryst Growth Des, 2017, 17(6): 3433-3442. doi: 10.1021/acs.cgd.7b00375
[55]	Pui Y, Chen YJ, Chen HJ, et al. Maintaining supersaturation of nimodipine by PVP with or without the presence of sodium lauryl sulfate and sodium taurocholate[J]. Mol Pharm, 2018, 15(7): 2754-2763. doi: 10.1021/acs.molpharmaceut.8b00253
[56]	Yang RC, Zhang GGZ, Kjoller K, et al. Phase separation in surfactant-containing amorphous solid dispersions: orthogonal analytical methods to probe the effects of surfactants on morphology and phase composition[J]. Int J Pharm, 2022, 619: 121708. doi: 10.1016/j.ijpharm.2022.121708
[57]	França MT, Marcos TM, Pereira RN, et al. Could the small molecules such as amino acids improve aqueous solubility and stabilize amorphous systems containing griseofulvin [J] ? Eur J Pharm Sci, 2020, 143 : 105178.
[58]	Jiang H, Zhang DK, Han X, et al. Research progress of solid dispersion of porous material as carrier to improve the dissolution rate of poorly water-soluble drugs[J]. Chin Pharm J (中国药学杂志), 2017, 52(17): 1477-1482.
[59]	Numpilai T, Muenmee S, Witoon T. Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen[J]. Mater Sci Eng C Mater Biol Appl, 2016, 59: 43-52. doi: 10.1016/j.msec.2015.09.095
[60]	Santos HA, Peltonen L, Limnell T, et al. Mesoporous materials and nanocrystals for enhancing the dissolution behavior of poorly water-soluble drugs[J]. Curr Pharm Biotechnol, 2013, 14(10): 926-938.
[61]	Mah PT, Peltonen L, Novakovic D, et al. The effect of surfactants on the dissolution behavior of amorphous formulations[J]. Eur J Pharm Biopharm, 2016, 103: 13-22. doi: 10.1016/j.ejpb.2016.03.007
[62]	de Martins RM, da Silva CA, Becker CM, et al. Interaction of (hydroxypropyl) cellulose with anionic surfactants in dilute regime[J]. Colloid Polym Sci, 2006, 284(12): 1353-1361. doi: 10.1007/s00396-006-1497-4
[63]	Shi Q, Cheng J, Li F, et al. Molecular mobility and crystal growth in amorphous binary drug delivery systems: effects of low-concentration poly(ethylene oxide)[J]. AAPS PharmSciTech, 2020, 21(8): 317. doi: 10.1208/s12249-020-01869-9
[64]	Zhang J, Shi Q, Tao J, et al. Impact of polymer enrichment at the crystal-liquid interface on crystallization kinetics of amorphous solid dispersions[J]. Mol Pharm, 2019, 16(3): 1385-1396. doi: 10.1021/acs.molpharmaceut.8b01331
[65]	Zhang J, Shi Q, Guo MS, et al. Melt crystallization of indomethacin polymorphs in the presence of poly(ethylene oxide): selective enrichment of the polymer at the crystal-liquid interface[J]. Mol Pharm, 2020, 17(6): 2064-2071. doi: 10.1021/acs.molpharmaceut.0c00220
[66]	Yao X, Benson EG, Gui Y, et al. Surfactants accelerate crystallization of amorphous nifedipine by similar enhancement of nucleation and growth independent of hydrophilic-lipophilic balance[J]. Mol Pharm, 2022, 19(7): 2343-2350. doi: 10.1021/acs.molpharmaceut.2c00156
[67]	Kapourani A, Tzakri T, Valkanioti V, et al. Drug crystal growth in ternary amorphous solid dispersions: effect of surfactants and polymeric matrix-carriers[J]. Int J Pharm X, 2021, 3: 100086.

[1]	WANG Shihao, LIU Lifeng, DING Yang, LI Suxin. Research progress of pH-responsive drug delivery systems in cancer immunotherapy[J]. Journal of China Pharmaceutical University, 2024, 55(4): 522-529. DOI: 10.11665/j.issn.1000-5048.2024011902
[2]	WU Yaqi, LI Meng, XING Haonan, CHEN Daquan, ZHENG Aiping. Research progress of nasal mucosal immunization vaccine against COVID-19[J]. Journal of China Pharmaceutical University, 2022, 53(6): 643-650. DOI: 10.11665/j.issn.1000-5048.20220602
[3]	BAO Xiaoqiang. Effects of co-culture supernatant of Lactobacillus casei and Bacillus subtiliis natto on intestinal microecology, mucosal barrier function and immune function in mice with antibiotic-associated diarrhea[J]. Journal of China Pharmaceutical University, 2020, 51(1): 92-98. DOI: 10.11665/j.issn.1000-5048.20200114
[4]	JIANG Liangliang, JIANG Tao, LUO Jianhua, YAO Wenbing, TIAN Hong. A novel human immune system mice model for assessing the immunogenicity of cancer vaccines[J]. Journal of China Pharmaceutical University, 2019, 50(6): 734-742. DOI: 10.11665/j.issn.1000-5048.20190615
[5]	HE Yu, TIAN Hong, DAI Xin, YAO Wenbing, GAO Xiangdong. Immunogenicity of HER2 vaccine containing p-nitrophenylalanine[J]. Journal of China Pharmaceutical University, 2018, 49(3): 369-375. DOI: 10.11665/j.issn.1000-5048.20180317
[6]	HAO Tianyun, GAO Yuan, WEI Yuanfeng, ZHANG Jianjun, QIAN Shuai. Strategies in transdermal and mucosal drug delivery systems:role of lyotropic liquid crystal[J]. Journal of China Pharmaceutical University, 2018, 49(2): 173-180. DOI: 10.11665/j.issn.1000-5048.20180206
[7]	NING Hongyu, JIANG Tao, ZHANG Rui, HE Yu, YAO Wenbing, TIAN Hong. Effects of immunogenic HER2 on the differentiation of T-cell in mouse[J]. Journal of China Pharmaceutical University, 2018, 49(1): 102-108. DOI: 10.11665/j.issn.1000-5048.20180115
[8]	LU Wei-dong, LIN Yi-ju, DAI Yun-bo, YANG Xuan-xiang, MA Bo. Preparation and immunogenicity of influenza vaccine lyophilized liposomes[J]. Journal of China Pharmaceutical University, 2009, 40(3): 218-221.
[10]	Study on the Immunogenity of Antigen and Antigenic Epitope Displayed by Phage Display of pIII and pVIII[J]. Journal of China Pharmaceutical University, 2004, (6): 100-105.

Cited By

Cited by

Periodical cited type(1)

敖日格乐. 蝎毒抗菌肽在病原微生物感染中的作用. 中国病原生物学杂志. 2024(12): 1521-1524 .

Other cited types(0)

Get Citation

PDF

XML

Article views (509) PDF downloads (53) Cited by(1)

Turn off MathJax

Article Contents

Abstract

References

Effects of pharmaceutical excipients on drug supersaturation in amorphous solid dispersions