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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Manipulation of Pharmaceutical Polymorphic Transformation Process Using Excipients

Author(s): Beiqian Tian, Zhiyong Ding, Shuyi Zong, Jinyue Yang, Na Wang, Ting Wang, Xin Huang and Hongxun Hao*

Volume 26, Issue 21, 2020

Page: [2553 - 2563] Pages: 11

DOI: 10.2174/1381612826666200213122302

Price: $65


Background: In the pharmaceutical field, it is vital to ensure a consistent product containing a single solid-state form of the active pharmaceutical ingredient (API) in the drug product. However, some APIs are suffering from the risk of transformation of their target forms during processing, formulation and storage.

Methods: The purpose of this review is to summarize the relevant category of excipients and demonstrate the availability and importance of using excipients as a key strategy to manipulate pharmaceutical polymorphic transformation.

Results: The excipient effects on solvent-mediated phase transformations, solid-state transitions and amorphous crystallization are significant. Common pharmaceutical excipients including amino acids and derivatives, surfactants, and various polymers and their different manipulation effects were summarized and discussed.

Conclusion: Appropriate use of excipients plays a role in manipulating polymorphic transformation process of corresponding APIs, with a promising application of guaranteeing the stability and effectiveness of drug dosage forms.

Keywords: Manipulation, APIs, excipients, polymorphic transformation, amorphous, stability.

« Previous
Bernstein J. Polymorphism in molecular crystals OxfordClarendon Press. New York: Oxford University Press 2002.
Cruz-Cabeza AJ, Bernstein J. Conformational Polymorphism. Chem Rev 2014; 114: 2170-91.
Raw AS, Furness MS, Gill DS, Adams RC, Holcombe FO, Yu LX. Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs). Adv Drug Deliv Rev 2004; 56: 397-414.
Ouyang L, Zheng T, Shen L. Direct observation of α- to β-glycine transformation during the ionic liquid-mediated crystallization processs. CrystEngComm 2018; 20: 2705-12.
Hachuła B. The nature of hydrogen-bonding interactions in nonsteroidal anti-inflammatory drugs revealed by polarized IR spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc 2018; 188: 189-96.
Bellich B, Di Fonzo S, Tavagnacco L, et al. Myelography Iodinated Contrast Media. 2. Conformational Versatility of Iopamidol in the Solid State. Mol Pharm 2017; 14(2): 468-77.
[] [PMID: 28059514]
Rani J, Raveendran A. Sushila, Chaudhary A, Panda MK, Patra R. Polymorphism in Sn(IV)-Tetrapyridyl Porphyrins with a Halogenated Axial Ligand. Structural, Photophysical, and Morphological Study. Cryst Growth Des 2018; 18: 1437-47.
Ito M, Shiba R, Watanabe M, Iwao Y, Itai S, Noguchi S. Phase transitions of antibiotic clarithromycin forms I, IV and new form VII crystals. Int J Pharm 2018; 547: 258-64.
Gopi SP, Banik M, Desiraju GR. New cocrystals of hydrochlorothiazide: Optimizing solubility and membrane diffusivity. Cryst Growth Des 2017; 17: 308-16.
Williams HD, Trevaskis NL, Charman SA, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev 2013; 65: 315-499.
Song Y, Zhu P, Wu Y, et al. Epsilon-poly-l-lysine decorated ordered mesoporous silica contributes to the synergistic antifungal effect and enhanced solubility of a lipophilic drug. Mater Sci Eng C Mater Biol Appl 2019; 99: 231-40.
Danda LJ de A, Batista L de M, Melo VCS, Soares Sobrinho JL, Soares MF de LR. Combining amorphous solid dispersions for improved kinetic solubility of posaconazole simultaneously released from soluble PVP/VA64 and an insoluble ammonio methacrylate copolymer. Eur J Pharm Sci 2019; 133: 79-85.
Lin S-Y. An overview of famotidine polymorphs: solid-state characteristics, thermodynamics, polymorphic transformation and quality control. Pharm Res 2014; 31(7): 1619-31.
[] [PMID: 24577998]
Novakovic D, Isomaki A, Pleunis B, et al. Understanding dissolution and crystallization with imaging: A surface point of view. Mol Pharm 2018; 15: 5361-73.
Nilsson Lill SO, Widdifield CM, Pettersen A, et al. Elucidating an amorphous form stabilization mechanism for tenapanor hydrochloride: crystal structure analysis using X-ray diffraction, NMR crystallography, and molecular modeling. Mol Pharm 2018; 15(4): 1476-87.
[] [PMID: 29490140]
Bhavana V, Chavan RB, Mannava MKC, Nangia A, Shastri NR. Quantification of niclosamide polymorphic forms - A comparative study by Raman, NIR and MIR using chemometric techniques. Talanta 2019; 199: 679-88.
Xu T, Nahar K, Dave R, Bates S, Morris K. Polymorphic transformation of indomethacin during hot melt extrusion granulation: process and dissolution control. Pharm Res 2018; 35(7): 140.
[] [PMID: 29748722]
Davis TD, Peck GE, Stowell JG, Morris KR, Byrn SR. Modeling and monitoring of polymorphic transformations during the drying phase of wet granulation. Pharm Res 2004; 21: 860-6.
Bouvart N, Palix R-M, Arkhipov SG, Tumanov IA, Michalchuk AAL, Boldyreva EV. Polymorphism of chlorpropamide on liquid-assisted mechanical treatment: choice of liquid and type of mechanical treatment matter. CrystEngComm 2018; 20: 1797-803.
Belenguer AM, Lampronti GI, De Mitri N, Driver M, Hunter CA, Sanders JKM. Understanding the influence of surface solvation and structure on polymorph stability: A combined mechanochemical and theoretical approach. J Am Chem Soc 2018; 140: 17051-9.
Nicoud L, Licordari F, Myerson AS. Estimation of the solubility of metastable polymorphs. Crit Rev 2018; 18: 7228-37.
Wang G, Ma Y, Wang Y, Hao H, Jiang Y. Investigation of solution-mediated phase transformation of cefuroxime acid to its acetonitrile solvate. Org Process Res Dev 2015; 19: 1820-5.
O’Mahony MA, Seaton CC, Croker DM, Veesler S, Rasmuson ÅC, Hodnett BK. Investigation into the mechanism of solution-mediated transformation from FI to FIII carbamazepine: The role of dissolution and the interaction between polymorph surfaces. Cryst Growth Des 2013; 13: 1861-71.
Maher A, Croker DM, Rasmuson ÅC, Hodnett BK. Solution Mediated Polymorphic Transformation. Form II to Form III Piracetam in Ethanol. Cryst Growth Des 2012; 12: 6151-7.
Byrn SR, Pfeiffer RR, Stowell JG, Byrn SR. Solid-state chemistry of drugs 1999.
Zhu B, Zhang Q, Ren G, Mei X. Solid-state characterization and insight into transformations and stability of apatinib mesylate solvates. Cryst Growth Des 2017; 17: 5994-6005.
Zakharov BA, Boldyreva EV. High pressure: A complementary tool for probing solid-state processes. CrystEngComm 2018; 21: 10-22.
Manimunda P, Asif SAS, Mishra MK. Probing stress induced phase transformation in aspirin polymorphs using Raman spectroscopy enabled nanoindentation. Chem Comm 2019; 55: 9200-3.
Zaczek AJ, Catalano L, Naumov P, Korter TM. Mapping the polymorphic transformation gateway vibration in crystalline 1,2,4,5-tetrabromobenzene. Chem Sci 2019; 10: 1332-41.
Fung MH, DeVault M, Kuwata KT, Suryanarayanan R. Drug-excipient interactions. Mol Pharm 2018; 15(3): 1052-61.
[] [PMID: 29309158]
Beran GJ. Modeling polymorphic molecular crystals with electronic structure theory. Chem Rev 2016; 116: 5567-613.
Abraham J. International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use In: Tietje C, Brouder A, Eds. . Handbook of Transnational Economic Governance Regimes.
Chavan RB, Bhargavi N, Lodagekar A, Shastri NR. Near infra red spectroscopy: A tool for solid state characterization. Drug Discov Today 2017; 22: 1835-43.
Antonio M, Maggio RM. Assessment of mefenamic acid polymorphs in commercial tablets using chemometric coupled to MIR and NIR spectroscopies. Prediction of dissolution performance. J Pharm Biomed Anal 2018; 149: 603-11.
Ghazani SM, Marangoni AG. The stability and nature of the form iv polymorph of cocoa butter is dictated by 1-Palmitoyl-2-Oleoyl-3-Stearoyl-Glycerol. Cryst Growth Des 2019; 19(3): 1488-93.
Koranne S, Krzyzaniak JF, Luthra S, Arora KK, Suryanarayanan R. Role of coformer and excipient properties on the solid-state stability of theophylline cocrystals. Cryst Growth Des 2019; 19: 868-75.
Zheng Y, Zhou J, Du F, et al. Formation of mesomorphic polymorph, thermal-induced phase transition, and crystalline structure-dependent degradable and mechanical properties of poly(p-dioxanone). Cryst Growth Des 2019; 19: 166-76.
Bayés-García L, Aguilar-Jiménez M, Calvet T, Koyano T, Sato K. crystallization and melting behavior of cocoa butter in lipid bodies of fresh cacao beans. Cryst Growth Des 2019; 19: 4127-37.
Larkin PJ, Dabros M, Sarsfield B, Chan E, Carriere JT, Smith BC. Polymorph characterization of active pharmaceutical ingredients (APIs) using low-frequency Raman spectroscopy. Appl Spectrosc 2014; 68(7): 758-76.
[] [PMID: 25014842]
Liu L, Cheng Y, Sun X, Pi F. Numerical modeling of polymorphic transformation of oleic acid via near-infrared spectroscopy and factor analysis. Spectrochim Acta A Mol Biomol Spectreosc 2018; 197: 153-58.
Ruggiero MT, Zeitler JA, Korter TM. Concomitant polymorphism and the martensitic-like transformation of an organic crystal. Phys Chem Chem Phys 2017; 19: 28502-6.
Cha J, Gilmor T, Lane P, Ranweiler JS. 12 - Stability Studies. In: Ahuja S, Scypinski S, Eds. . Separation Science and Technology. Academic Press 2011; Vol. 10: pp. 459-505.
Singh H, Khurana LK, Singh R. Pharmaceutical Development. In: Vohora D, Singh G, Eds. . Pharmaceutical Medicine and Translational Clinical Research.. Boston: Academic Press 2018; pp. 33-46.
Poozesh S, Setiawan N, Arce F, et al. Understanding the process-product-performance interplay of spray dried drug-polymer systems through complete structural and chemical characterization of single spray dried particles. Powder Tech 2017; 320: 685-95.
Baaklini G, Dupray V, Coquerel G. Inhibition of the spontaneous polymorphic transition of pyrazinamide γ form at room temperature by co-spray drying with 1,3-dimethylurea. Int J Pharm 2015; 479: 163-70.
Lu X, Huang C, Lowinger MB, et al. Molecular interactions in posaconazole amorphous solid dispersions from two-dimensional solid-state NMR spectroscopy. Mol Pharmaceutics 2019; 16: 2579-89.
Peng T-X, Liang D-S, Guo F, et al. Enhanced storage stability of solid lipid nanoparticles by surface modification of comb-shaped amphiphilic inulin derivatives. Coll Surf B Biointer 2019; 181: 369-78.
Schammé B, Couvrat N, Tognetti V, et al. Investigation of drug-excipient interactions in biclotymol amorphous solid dispersions. Mol Pharm 2018; 15: 1112-25.
Chavan RB, Shastri NR. Polymorphic transformation as a result of atovaquone incompatibility with selected excipients. J Thermal Anal Calorimetry 2018; 131: 2129-39.
Deshpande TM, Shi H, Pietryka J, Hoag SW, Medek A. Investigation of polymer/surfactant interactions and their impact on itraconazole solubility and precipitation kinetics for developing spray-dried amorphous solid dispersions. Mol Pharm 2018; 15: 962-74.
Betigeri S, Thakur A, Shukla R, Raghavan K. Effect of polymer additives on the transformation of BMS-566394 anhydrate to the dihydrate form. Pharm Res 2008; 25: 1043-51.
Antonio M, Calvo NL, Maggio RM. Chemometric study of the excipients’ influence on polymorphic-behavior. Mefenamic acid as case of study. J Pharm Biomed Anal 2019; 170: 8-15.
Paisana MC, Wahl MA, Pinto JF. An insight into the impact of polymers on the hydrate conversion of olanzapine form I in aqueous suspensions. J Pharm Sci 2017; 106: 1786-94.
Dempah KE, Barich DH, Kaushal AM, et al. Investigating gabapentin polymorphism using solid-state NMR spectroscopy. AAPS PharmSciTech 2013; 14: 19-28.
Shi N-Q, Jin Y, Zhang Y, et al. The influence of cellulosic polymer’s variables on dissolution/solubility of amorphous felodipine and crystallization inhibition from a supersaturated state. AAPS PharmSciTech 2018; 20(12)
Doreth M, Löbmann K, Priemel P, et al. Influence of PVP molecular weight on the microwave assisted in situ amorphization of indomethacin. Eur J Pharm Biopharm 2018; 122: 62-9.
Mo Y, Dang L, Wei H. l-Glutamic Acid Polymorph Control Using Amino Acid Additives. Ind Eng Chem Res 2011; 50: 10385-92.
Shimizu T, Yoshiura H, Nagano H, Hirasawa I. Effect of specific amino acids on controlling crystal pseudopolymorphism of L-Arginine hydrochloride. Chem Eng Technol 2014; 37: 1427-30.
Zhang J, Cao X, Ji S, Lan P, Liao A. Solubility and transformation behavior of l-phenylalanine anhydrate with amino acid additives. J Therm Anal Calori 2018; 131: 1777-81.
Li Z, Shi P, Yang Y, et al. Tuning crystallization and stability of the metastable polymorph of dl-methionine by a structurally similar additive. CrystEngComm 2019; 21: 3731-9.
Wang J, Yang L, Li D, et al. Investigating the mechanism of l-valine in improving the stability of gabapentin combining chemical analysis experiments with computational pharmacy. AAPS Pharm Sci Tech 2019; 20(114)
Lee EH, Byrn SR. Stabilization of metastable flufenamic acid by inclusion of mefenamic acid: solid solution or epilayer? J Pharm Sci 2010; 99(9): 4013-22.
[] [PMID: 20589947]
Airaksinen S, Luukkonen P, Jørgensen A, Karjalainen M, Rantanen J, Yliruusi J. Effects of excipients on hydrate formation in wet masses containing theophylline. J Pharm Sci 2003; 92: 516-28.
Krūkle-Bērziņa K, Actiņš A. The effect of excipients on the stability and phase transition rate of xylazine hydrochloride and zopiclone. J Pharm Biomed Anal 2015; 107: 168-74.
Tinmanee R, Stamatis SD, Ueyama E, Morris KR, Kirsch LE. Polymorphic and covalent transformations of gabapentin in binary excipient mixtures after milling-induced stress. Pharm Res 2018; 35: 39.
Tinmanee R, Larsen SC, Morris KR, Kirsch LE. Quantification of gabapentin polymorphs in gabapentin/excipient mixtures using solid state 13C NMR spectroscopy and X-ray powder diffraction. J Pharm Biomed Anal 2017; 146: 29-36.
Forgan RS, Smaldone RA, Gassensmith JJ, et al. Nanoporous carbohydrate metal-organic frameworks. J Am Chem Soc 2012; 134: 406-17.
Lin S-Y, Hsu C-H, Ke W-T. Solid-state transformation of different gabapentin polymorphs upon milling and co-milling. Int J Pharm 2010; 396: 83-90.
Sonoda Y, Hirayama F, Arima H, Yamaguchi Y, Saenger W, Uekama K. Selective crystallization of the metastable form IV polymorph of tolbutamide in the presence of 2,6-Di- O -methyl-β-cyclodextrin in aqueous solution. Cryst Growth Des 2006; 6: 1181-5.
Ishiguro T, Hirayama F, Iohara D, Uekama K. Prominent inhibitory effect of 2-hydroxybutyl-β-cyclodextrin on solution-mediated polymorphic transition of chlorpropamide. Chem Letters 2008; 37: 816-7.
Ishiguro T, Hirayama F, Iohara D, Arima H, Kaneto Uekama. Crystallization and polymorphic transitions of chlorpropamide in aqueous 2-hydroxybutyl-β-cyclodextrin solution. Eur J Pharm Sci 2010; 39: 248-55.
Paaver U, Lust A, Mirza S, et al. Insight into the solubility and dissolution behavior of piroxicam anhydrate and monohydrate forms. Int J Pharm 2012; 431: 111-9.
Kirchmeyer W, Grassmann O, Wyttenbach N, Alsenz J, Kuentz M. Miniaturized X-ray powder diffraction assay (MixRay) for quantitative kinetic analysis of solvent-mediated phase transformations in pharmaceutics. J Pharma Biomed Anal 2016; 131: 195-201.
Huang C, Klinzing G, Procopio A, et al. understanding compression-induced amorphization of crystalline posaconazole. Mol Pharm 2019; 16: 825-33.
Kirchmeyer W, Wyttenbach N, Alsenz J, Kuentz M. Influence of excipients on solvent-mediated hydrate formation of piroxicam studied by dynamic imaging and fractal analysis. Cryst Growth Des 2015; 15: 5002-10.
Smets MMH, Baaklini G, Tijink A, et al. Inhibition of the vapor-mediated phase transition of the high temperature form of pyrazinamide. Cryst Growth Des 2018; 18: 1109-16.
Bertoni S, Albertini B, Ferraro L, Beggiato S, Dalpiaz A, Passerini N. Exploring the use of spray congealing to produce solid dispersions with enhanced indomethacin bioavailability: In vitro characterization and in vivo study. Eur J Pharm Biopharm 2019; 139: 132-41.
Zhang J, Wu C-Y, Pan X, Wu C. On identification of critical material attributes for compression behaviour of pharmaceutical diluent powders. Materials (Basel) 2017; 10(845)
Rowe RC, Ed. Handbook of pharmaceutical excipients. London: APhA, (PhP) Pharmaceutical Press 2009.
Wildfong PLD, Morris KR, Anderson CA, Short SM. Demonstration of a shear-based solid-state phase transformation in a small molecular organic system: Chlorpropamide. J Pharm Sci 2007; 96(5): 1100-13.
[] [PMID: 17455336]
Thakral NK, Thakral S, Stephenson GA, Sedlock R, Suryanarayanan R. Compression-induced polymorphic transformation in tablets: role of shear stress and development of mitigation strategies. J Pharm Sci 2019; 108(1): 476-84.
[] [PMID: 30248335]
Juban A, Briançon S, Puel F. Processing-induced-transformations (PITs) during direct compression: Impact of tablet composition and compression load on phase transition of caffeine. Int J Pharm 2016; 501: 253-64.
Thakral S, Garcia-Barriocanal J, Thakral NK. Effect of processing conditions and excipients on dehydration kinetics of sodium naproxen hydrate in formulation. Int J Pharm 2019; 557: 221-8.
Otsuka M, Ohfusa T, Matsuda Y. Effect of binders on polymorphic transformation kinetics of carbamazepine in aqueous solution. Coll Surf B: Biointer 2000; 17: 145-52.
Potter CB, Kollamaram G, Zeglinski J, Whitaker DA, Croker DM, Walker GM. Investigation of polymorphic transitions of piracetam induced during wet granulation. Eur J Pharm Biopharm 2017; 119: 36-46.
Yao C, Li Y, Wang L, et al. Tuning the solution-mediated concomitant phase transformation outcome of the piroxicam monohydrate by two hydroxyl-containing additives: hydroxypropyl cellulose and H2O. Cryst Growth Des 2019; 19: 583-90.
Qu H, Louhi-Kultanen M, Kallas J. Additive Effects on the Solvent-Mediated Anhydrate/Hydrate Phase Transformation in a Mixed Solvent. Cryst Growth Des 2007; 7: 724-9.
Skrdla PJ. Physicochemically relevant modeling of nucleation-and-growth kinetics. investigation of additive effects on the solvent-mediated phase transformation of carbamazepine. Cryst Growth Des 2008; 8: 4185-9.
Wikström H, Carroll WJ, Taylor LS. Manipulating theophylline monohydrate formation during high-shear wet granulation through improved understanding of the role of pharmaceutical excipients. Pharm Res 2008; 25: 923-35.
Liu Y, Gao H, Xu H, Ren F, Ren G. Influence of temperature, solvents, and excipients on crystal transformation of agomelatine. Organic Process Res Dev 2016; 20: 1559-65.
Tian F, Sandler N, Aaltonen J, et al. Influence of polymorphic form, morphology, and excipient interactions on the dissolution of carbamazepine compacts. J Pharm Sci 2007; 96: 584-94.
Zhang S, Britten JF, Chow AHL, Lee TWY. Impact of crystal structure and polymer excipients on the melt crystallization kinetics of itraconazole polymorphs. Cryst Growth Des 2017; 17: 3433-42.
Li N, Taylor LS. Tailoring supersaturation from amorphous solid dispersions. J Control Release 2018; 279: 114-25.
Jenning V, Schafer-Korting M, Gohla S. Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. J Control Release 2000; 66: 115-26.
Whittam JH, Rosano HL. Physical aging of even saturated monoacid triglycerides. J Am Oil Chem Soc 1975; 52: 128-33.
Joseph S, Rappolt M, Schoenitz M, et al. Stability of the metastable α-polymorph in solid triglyceride drug-carrier nanoparticles. Langmuir 2015; 31: 6663-74.
Rosenblatt KM, Bunjes H. Poly(vinyl alcohol) as emulsifier stabilizes solid triglyceride drug carrier nanoparticles in the α-modification. Mol Pharm 2009; 6: 105-20.
Gift AD, Southard LA, Riesberg AL. Influence of polymeric excipient properties on crystal hydrate formation kinetics of caffeine in aqueous slurries. J Pharm Sci 2012; 101: 1755-62.
Gift AD, Luner PE, Luedeman L, Taylor LS. Manipulating hydrate formation during high shear wet granulation using polymeric excipients. J Pharm Sci 2009; 98: 4670-83.
Scaramuzza D, Schneider Rauber G, Voinovich D, Hasa D. Dehydration without Heating. Use of Polymer-Assisted Grinding for Understanding the Stability of Hydrates in the Presence of Polymeric Excipients. Cryst Growth Des 2018; 18: 5245-53.
Vitz J, Majdanski TC, Meier A, Lutz PJ, Schubert US. Polymerization of ethylene oxide under controlled monomer addition via a mass flow controller for tailor made polyethylene oxides. Polymer Chem 2016; 7: 4063-71.
Schmidt AG, Wartewig S, Picker KM. Polyethylene oxides: Protection potential against polymorphic transitions of drugs? J Raman Spectroscopy 2004; 35: 360-7.
Raijada D, Arnfast L, Bond AD, et al. Dehydration of nitrofurantoin monohydrate during melt extrusion. Cryst Growth Des 2017; 17: 3707-15.
Zhang J, Shi Q, Tao J, Peng Y, Cai T. Impact of polymer enrichment at the crystal-liquid interface on crystallization kinetics of amorphous solid dispersions. Mol Pharm 2019; 16: 1385-96.
Paisana MC, Wahl MA, Pinto JF. Effect of polymers in moisture sorption and physical stability of polymorphic olanzapine. Eur J Pharm Sci 2017; 97: 257-68.
Paisana M, Wahl M, Pinto J. Role of polymeric excipients in the stabilization of olanzapine when exposed to aqueous environments. Molecules 2015; 20: 22364-82.
Nunes C, Mahendrasingam A, Suryanarayanan R. Investigation of the multi-step dehydration reaction of theophylline monohydrate using 2-dimensional powder X-ray diffractometry. Pharm Res 2006; 23: 2393-404.
Nair R, Gonen S, Hoag SW. Influence of polyethylene glycol and povidone on the polymorphic transformation and solubility of carbamazepine. Int J Pharm 2002; 240: 11-22.
Tian F, Saville DJ, Gordon KC, et al. The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension. J Pharm Pharmacol 2007; 59: 193-201.
Kalitnik AA, Karetin YA, Kravchenko AO, Khasina EI, Yermak IM. Influence of carrageenan on cytokine production and cellular activity of mouse peritoneal macrophages and its effect on experimental endotoxemia. J Biomed Mater Res A 2017; 105: 1549-57.
Volod’ko AV, Davydova VN, Chusovitin E, et al. Soluble chitosan-carrageenan polyelectrolyte complexes and their gastroprotective activity. Carbohydr Polym 2014; 101: 1087-93.
Schmidt AG, Wartewig S, Picker KM. Potential of carrageenans to protect drugs from polymorphic transformation. Eur J Pharm Biopharm 2003; 56: 101-5.

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