Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Capillary-Based Techniques for Physical-Chemical Characterization of Drug Substances and Drug Delivery Systems

  • Chapter
  • First Online:
Analytical Techniques in the Pharmaceutical Sciences

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Physical chemical characterization of drug compounds and drug delivery systems is challenging when the amount of material for analysis is limited. Capillary-based methodologies based on capillary electrophoresis (CE) or Taylor Dispersion Analysis (TDA) present a number of advantages as they are characterized by being fast, require a very limited amount of sample material, are easy to automate and highly versatile. Different methods may be applied leading to a range of physical chemical properties being probed for the same sample using the same instrumentation. The term affinity CE covers a range of approaches for assessing important physical chemical parameters such as non-covalent affinity constants, pKa values as well as partition/distribution coefficients measured by quantifying partitioning into microemulsions and micelles. On the other hand, TDA provides data on diffusivities and hydrodynamic radius as well as viscosity. A variant of this technique termed Flow Induced Dispersion Analysis (FIDA) may be used to quantify non-covalent affinity interactions for charged as well as neutral species. The present chapter highlights novel features of capillary based methods in profiling physical chemical properties of drug compounds and drug delivery systems. A number of feasible applications are described, which may serve as an inspiration in delivery science and technology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Albarghouthi MN, Stein TM, Barron AE (2003) Poly-N-hydroxyethylacrylamide as a novel, adsorbed coating for protein separation by capillary electrophoresis. Electrophoresis 24:1166–1175

    Article  CAS  PubMed  Google Scholar 

  • Annovazzi L, Viglio S, Perani E, Luisetti M, Baraniuk J, Casado B, Cetta G, Iadarola P (2004) Capillary electrophoresis with laser-induced fluorescence detection as a novel sensitive approach for the analysis of desmosines in real samples. Electrophoresis 25:683–691

    Article  CAS  PubMed  Google Scholar 

  • Babic S, Horvat AJM, Pavlovic DP, Kastelan-Macan M (2007) Determination of pKa values of active pharmaceutical ingredients. Trends Anal Chem 26:1043–1061

    Article  CAS  Google Scholar 

  • Bello MS, Rezzonico R, Righetti PG (1994) Use of Taylor-Aris dispersion for measurement of a solute diffusion-coefficient in thin capillaries. Science 266:773–776

    Article  CAS  PubMed  Google Scholar 

  • Belongia BM, Baygents JC (1997) Measurements on the diffusion coefficient of colloidal particles by Taylor-Aris dispersion. J Colloid Interface Sci 195:19–31

    Article  CAS  PubMed  Google Scholar 

  • Bendahl L, Hansen SH, Gammelgaard B (2001) Capillaries modified by noncovalent anionic polymer adsorption for capillary zone electrophoresis, micellar electrokinetic capillary chromatography and capillary electrophoresis mass spectrometry. Electrophoresis 22:2565–2573

    Article  CAS  PubMed  Google Scholar 

  • Bielejewska A, Bylina A, Duszczyk K, Fialkowski M, Holyst R (2010) Evaluation of ligand-selector interaction from effective diffusion coefficient. Anal Chem 82:5463–5469

    Article  CAS  PubMed  Google Scholar 

  • Cao LW, Tan XF, Li C, Wu C, Zhang ZD, Deng T, Meng JX (2013) Capillary electrophoresis-laser induced fluorescence detection of GABA and its analogs in human serum with solid-phase extraction and fluorescein-based probes. Anal Methods 5:6000–6008

    Article  CAS  Google Scholar 

  • Cottet H, Biron JP, Martin M (2007a) Taylor dispersion analysis of mixtures. Anal Chem 79:9066–9073

    Article  CAS  PubMed  Google Scholar 

  • Cottet H, Martin M, Papillaud A, Souaid E, Collet H, Commeyras A (2007b) Determination of dendrigraft poly-L-lysine diffusion coefficients by Taylor dispersion analysis. Biomacromolecules 8:3235–3243

    Article  CAS  PubMed  Google Scholar 

  • Cottet H, Biron JP, Cipelletti L, Matmour R, Martin M (2010) Determination of individual diffusion coefficients in evolving binary mixtures by Taylor dispersion analysis: application to the monitoring of polymer reaction. Anal Chem 82:1793–1802

    Article  CAS  PubMed  Google Scholar 

  • Cretich M, Chiari M, Pirri G, Crippa A (2005) Electroosmotic flow suppression in capillary electrophoresis: chemisorption of trimethoxy silane-modified polydimethylacrylamide. Electrophoresis 26:1913–1919

    Article  CAS  PubMed  Google Scholar 

  • Dribek M, Le Potier I, Rodrigues A, Pallandre A, Fattal E, Taverna M (2007) Determination of binding constants of vasoactive intestinal peptide to poly(amidoamine) dendrimers designed for drug delivery using ACE. Electrophoresis 28:2191–2220

    Article  CAS  PubMed  Google Scholar 

  • El Deeb S, Wätzig H, Abd El-Hady D (2013) Capillary electrophoresis to investigate biopharmaceuticals and pharmaceutically-relevant binding properties. Trends Anal Chem 48:112–131

    Article  CAS  Google Scholar 

  • Filipe V, Hawe A, Carpenter JF, Jiskoot W (2013) Analytical approaches to assess the degradation of therapeutic proteins. Trends Anal Chem 49:118–125

    Article  CAS  Google Scholar 

  • Franzen U, Østergaard J (2012) Physico-chemical characterization of liposomes and drug substance-liposome interactions in pharmaceutics using capillary electrophoresis and electrokinetic chromatography. J Chromatogr A 1267:32–44

    Article  CAS  PubMed  Google Scholar 

  • Franzen U, Jorgensen L, Larsen C, Heegaard NHH, Østergaard J (2009) Determination of liposome-buffer distribution coefficients of charged drugs by capillary electrophoresis frontal analysis. Electrophoresis 30:2711–2719

    Article  CAS  PubMed  Google Scholar 

  • Franzen U, Vermehren C, Jensen H, Ostergaard J (2011) Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis. Electrophoresis 32:738–748

    Article  CAS  PubMed  Google Scholar 

  • Gilges M, Kleemiss MH, Schomburg G (1994) Capillary zone electrophoresis separations of basic and acidic proteins using poly(vinyl alcohol) coatings in fused-silica capillaries. Anal Chem 66:2038–2046

    Article  CAS  Google Scholar 

  • Hawe A, Hulse WL, Jiskoot W, Forbes RT (2011) Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates. Pharm Res 28:2302–2310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heegaard NHH, Kennedy RT (1999) Identification, quantitation, and characterization of biomolecules by capillary electrophoretic analysis of binding interactions. Electrophoresis 20:3122–3133

    Article  CAS  PubMed  Google Scholar 

  • Heegaard NHH, Schou C, Østergaard J (2008) Analysis of proteins in solution using affinity capillary electrophoresis. In: Zachariou M (ed) Affinity chromatography: methods and protocols, 2nd edn. Humana Press, Totowa, pp 303–338

    Chapter  Google Scholar 

  • Henchoz Y, Bard B, Guillarme D, Carrupt P-A, Veuthey J-L, Martel S (2009) Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution. Anal Bioanal Chem 394:707–729

    Article  CAS  PubMed  Google Scholar 

  • Holm R, Schönbeck C, Askjær S, Jensen H, Westh P, Østergaard J (2011) Complexation of tauro- and glyco-conjugated bile salts with α-cyclodextrin and hydroxypropyl-α-cyclodextrin studied by affinity capillary electrophoresis and molecular modelling. J Sep Sci 34:3221–3230

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim A, Ohshima H, Allison SA, Cottet H (2012) Determination of effective charge of small ions, polyelectrolytes and nanoparticles by capillary electrophoresis. J Chromatogr A 1247:154–164

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim A, Meyrueix R, Pouliquen G, Chan YP, Cottet H (2013) Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis. Anal Bioanal Chem 405:5369–5379

    Article  CAS  PubMed  Google Scholar 

  • Ishihama Y, Nakamura M, Miwa T, Kajima T, Asakawa N (2002) A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery. J Pharm Sci 91:933–942

    Article  CAS  PubMed  Google Scholar 

  • Jensen H, Ostergaard J (2010) Flow induced dispersion analysis quantifies noncovalent interactions in nanoliter samples. J Am Chem Soc 132:4070–4071

    Article  CAS  PubMed  Google Scholar 

  • Jensen H, Østergaard J, Thomsen AE, Hansen SH (2007) CE frontal analysis based on simultaneous UV and contactless conductivity detection: a general setup for studying noncovalent interactions. Electrophoresis 28:322–327

    Article  CAS  PubMed  Google Scholar 

  • Jensen H, Larsen SW, Larsen C, Østergaard J (2013) Physicochemical profiling of drug candidates using capillary-based techniques. J Drug Del Tech 23:333–345

    Article  CAS  Google Scholar 

  • Jensen SS, Jensen H, Cornett C, Møller EH, Østergaard J (2014) Insulin diffusion and self-association characterized by real-time UV imaging and Taylor dispersion analysis. J Pharm Biomed Anal 92:203–210

    Article  CAS  PubMed  Google Scholar 

  • Jia Z (2005) Physicochemical profiling by capillary electrophoresis. Curr Pharm Anal 1:45–56

    Article  Google Scholar 

  • Jia Z, Choi DK, Chokshi H (2013) Determination of drug-polymer binding constants by affinity capillary electrophoresis for aryl propionic acid derivatives and related compounds. J Pharm Sci 102:960–966

    Article  CAS  PubMed  Google Scholar 

  • Kok WT (2000) Capillary electrophoresis: instrumentation and operation. Chromatographia 51:S5–S89

    Article  Google Scholar 

  • Kostal V, Katzenmeyer J, Arriaga EA (2008) Capillary electrophoresis in bioanalysis. Anal Chem 80:4533–4550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kraak JC, Busch S, Poppe H (1992) Study of protein-drug binding using capillary zone electrophoresis. J Chromatogr 608:257–264

    Article  CAS  PubMed  Google Scholar 

  • Kuban P, Hauser PC (2011) Capacitively coupled contactless conductivity detection for microseparation techniques—recent developments. Electrophoresis 32:30–42

    Article  CAS  PubMed  Google Scholar 

  • Le Saux T, Cottet H (2008) Size-based characterization by the coupling of capillary electrophoresis to Taylor dispersion analysis. Anal Chem 80:1829–1832

    Article  PubMed  Google Scholar 

  • Li SK, Liddell MR, Wen H (2011) Effective electrophoretic mobilities and charges of anti-VEGF proteins determined by capillary zone electrophoresis. J Pharm Biomed Anal 55:603–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin C-E (2004) Determination of critical micelle concentration of surfactants by capillary electrophoresis. J Chromatogr A 1037:467–478

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Dahdouh F, Salgado M, Gomez FA (2009) Recent advances in affinity capillary electrophoresis (2007). J Pharm Sci 98:394–410

    Article  CAS  PubMed  Google Scholar 

  • Mrestani Y, El-Mokdad N, Ruttinger HH, Neubert R (1998) Characterization of partitioning behavior of cephalosporins using microemulsion and micellar electrokinetic chromatography. Electrophoresis 19:2895–2899

    Article  CAS  PubMed  Google Scholar 

  • Mrestani Y, Behbood L, Härtl A, Neubert RHH (2010) Microemulsion and mixed micelle for oral administration as new drug formulations for highly hydrophilic drugs. Eur J Pharm Biopharm 74:219–222

    Article  CAS  PubMed  Google Scholar 

  • Neubert RHH, Rüttinger H-H (2003) Affinity capillary electrophoresis in pharmaceutics and biopharmaceutics. Marcel Dekker, New York

    Book  Google Scholar 

  • Nguyen TTTN, Østergaard J, Sturup S, Gammelgaard B (2012) Investigation of a liposomal oxaliplatin drug formulation by capillary electrophoresis hyphenated to inductively coupled plasma mass spectrometry (CE-ICP-MS). Anal Bioanal Chem 402:2131–2139

    Article  CAS  PubMed  Google Scholar 

  • Nguyen TTTN, Østergaard J, Sturup S, Gammelgaard B (2013a) Determination of platinum drug release and liposome stability in human plasma by CE-ICP-MS. Int J Pharm 449:95–102

    Article  CAS  PubMed  Google Scholar 

  • Nguyen TTTN, Østergaard J, Sturup S, Gammelgaard B (2013b) Metallomics in drug development: characterization of a liposomal cisplatin drug formulation in human plasma by CE-ICP-MS. Anal Bioanal Chem 405:1845–1854

    Article  CAS  PubMed  Google Scholar 

  • Oravcová J, Böhs B, Lindner W (1996) Drug-protein binding studies. New trends in analytical and experimental methodology. J Chromatogr B 677:1–28

    Article  Google Scholar 

  • Ôrnskov E, Linusson A, Folestad S (2003) Determination of dissociation constants of labile drug compounds by capillary electrophoresis. J Pharm Biomed Anal 33:379–391

    Article  PubMed  Google Scholar 

  • Örnskov E, Gottfries J, Erickson M, Folestad S (2005) Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions. J Pharm Pharmacol 57:435–442

    Article  PubMed  Google Scholar 

  • Østergaard J, Moeller EH (2010) Ghrelin–liposome interactions. Characterization of liposomal formulations of an acylated 28-amino acid peptide using capillary electrophoresis. Electrophoresis 31:339–345

    Article  PubMed  Google Scholar 

  • Østergaard J, Heegaard NHH (2003) Capillary electrophoresis frontal analysis: principles and applications for the study of drug-plasma protein binding. Electrophoresis 24:2903–2913

    Article  PubMed  Google Scholar 

  • Østergaard J, Heegaard NHH (2006) Bioanalytical interaction studies executed by preincubation affinity capillary electrophoresis. Electrophoresis 27:2590–2608

    Article  PubMed  Google Scholar 

  • Østergaard J, Jensen H (2009) Simultaneous evaluation of ligand binding properties and protein size by electrophoresis and Taylor dispersion analysis in capillaries. Anal Chem 81:8694–8698

    Article  Google Scholar 

  • Østergaard J, Schou C, Larsen C, Heegaard NHH (2002) Evaluation of capillary electrophoresis frontal analysis for the study of low molecular weight drug-human serum albumin interactions. Electrophoresis 23:2842–2853

    Article  PubMed  Google Scholar 

  • Østergaard J, Hansen SH, Larsen C, Schou C, Heegaard NHH (2003a) Determination of octanol-water partition coefficients for carbonate esters and other small organic molecules by microemulsion electrokinetic chromatography. Electrophoresis 24:1038–1046

    Article  PubMed  Google Scholar 

  • Østergaard J, Schou C, Larsen C, Heegaard NHH (2003b) Effect of dextran as a run buffer additive in drug-protein binding studies using capillary electrophoresis frontal analysis. Anal Chem 75:207–214

    Article  PubMed  Google Scholar 

  • Østergaard J, Hansen SH, Jensen H, Thomsen AE (2005) Pre-equilibrium capillary zone electrophoresis or frontal analysis: advantages of plateau peak conditions in affinity capillary electrophoresis. Electrophoresis 26:4050–4054

    Article  PubMed  Google Scholar 

  • Østergaard J, Jensen H, Holm R (2012) Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether-ss-cyclodextrin. J Sep Sci 35:2764–2772

    Article  PubMed  Google Scholar 

  • Pascoe RJ, Masucci JA, Foley JP (2006) Investigation of vesicle electrokinetic chromatography as an in vitro assay for the estimation of intestinal permeability of pharmaceutical drug candidates. Electrophoresis 27:793–804

    Article  CAS  PubMed  Google Scholar 

  • Poole SK, Patel S, Dehring K, Workman H, Poole CF (2004) Determination of acid dissociation constants by capillary electrophoresis. J Chromatogr A 1037:445–454

    Article  CAS  PubMed  Google Scholar 

  • Progent F, Taverna M, Le Potier I, Gopée F, Ferrier D (2002) A study on the binding between polymers and peptides, using affinity capillary electrophoresis, applied to polymeric drug delivery systems. Electrophoresis 23:938–944

    Article  CAS  PubMed  Google Scholar 

  • Sanger van de Griend CE, Groningsson K, Arvidsson T (1997) Enantiomeric separation of a tetrapeptide with cyclodextrin—extension of the model for chiral capillary electrophoresis by complex formation of one enantiomer molecule with more than one chiral selector molecules. J Chromatogr A 782:271–279

    Article  Google Scholar 

  • Schipper BR, Ramstad T (2005) Determination of the binding constant between alprostadil and alpha-cyclodextrin by capillary electrophoresis: implication for a freeze-dried formulation. J Pharm Sci 94:1528–1537

    Article  CAS  PubMed  Google Scholar 

  • Sharma U, Gleason NJ, Carbeck JD (2005) Diffusivity of solutes measured in glass capillaries using Taylor’s analysis of dispersion and a commercial CE instrument. Anal Chem 77:806–813

    Article  CAS  PubMed  Google Scholar 

  • Taylor G (1953) Dispersion of soluble matter in solvent flowing slowly through a tube. Proc R Soc London Ser A 219:186–203

    Article  CAS  Google Scholar 

  • Taylor G (1954) Conditions under which dispersion of a solute in a stream of solvent can be used to measure molecular diffusion. Proc R Soc London Ser A 225:473–477

    Article  CAS  Google Scholar 

  • Terabe S, Otsuka K, Ichikawa K, Tsuchiya A, Ando T (1984) Electrokinetic separations with micellar solutions and open-tubular capillaries. Anal Chem 56:111–113

    Article  CAS  Google Scholar 

  • Terabe S, Otsuka K, Ando T (1985) Electrokinetic chromatography with micellar solution and open-tubular capillary. Anal Chem 57:834–841

    Article  CAS  Google Scholar 

  • Trainor GL (2007) The importance of plasma protein binding in drug discovery. Expert Opin Drug Discov 2:54–61

    Article  Google Scholar 

  • Vespalec R, Bocek P (2000) Calculation of stability constants for the chiral selector-enantiomer interactions from electrophoretic mobilities. J Chromatogr A 875:431–445

    Article  CAS  PubMed  Google Scholar 

  • Vuignier K, Schappler J, Veuthey J-L, Carrupt P-A, Martel S (2010a) Improvement of a capillary electrophoresis/frontal analysis (CE/FA) method for determining binding constants: discussion on relevant parameters. J Pharm Biomed Anal 53:1288–1297

    Article  CAS  PubMed  Google Scholar 

  • Vuignier K, Schappler J, Veuthey J-L, Carrupt P-A, Martel S (2010b) Drug-protein binding: a critical review of analytical tools. Anal Bioanal Chem 398:53–66

    Article  CAS  PubMed  Google Scholar 

  • Vuignier K, Veuthey J-L, Carrupt P-A, Schappler J (2012) Characterization of drug-protein interactions by capillary electrophoresis hyphenated to mass spectrometry. Electrophoresis 33:3306–3315

    Article  CAS  PubMed  Google Scholar 

  • Wan H, Holmen AG (2009) High throughput screening of physicochemical properties and in vitro ADME profiling in drug discovery. Comb Chem High Throughput Screen 12:315–329

    Article  CAS  PubMed  Google Scholar 

  • Wan H, Östlund Ã…, Jönsson S, Lindberg W (2005) Single run measurements of drug-protein binding by high-performance frontal analysis capillary electrophoresis and mass spectrometry. Rapid Commun Mass Spectrom 19:1603–1610

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Sun J, Liu H, Wang Y, He Z (2007) Prediction of human drug absorption using liposome electrokinetic chromatography. Chromatographia 65:173–177

    Article  Google Scholar 

  • Wang YJ, Sun J, Liu HZ, Liu JF, Zhang LQ, Liu K, He ZG (2009) Predicting skin permeability using liposome electrokinetic chromatography. Analyst 134:267–272

    Article  CAS  PubMed  Google Scholar 

  • Xian DL, Huang KL, Liu SQ, Xiao JY (2008) Quantitative retention-activity relationship studies by liposome electrokinetic chromatography to predict skin permeability. Chin J Chem 26:671–676

    Article  CAS  Google Scholar 

  • Ye FB, Jensen H, Larsen SW, Yaghmur A, Larsen C, Ostergaard J (2012) Measurement of drug diffusivities in pharmaceutical solvents using Taylor dispersion analysis. J Pharm Biomed Anal 61:176–183

    Article  CAS  PubMed  Google Scholar 

  • Ye F, Xie Y, Jensen H, Larsen SW, Yaghmur A, Larsen C, Østergaard J (2013) Interaction of amino acid and dipeptide â-naphthylamide derivatives with hyaluronic acid and human serum albumin studied by capillary electrophoresis frontal analysis. Chromatographia 76:49–57

    Article  CAS  Google Scholar 

  • Zavaleta J, Chinchilla D, Brown A, Ramirez A, Calderon V, Sogomonyan T, Gomez FA (2006) Recent developments in affinity capillary electrophoresis: a review. Curr Anal Chem 2:35–42

    Article  CAS  Google Scholar 

  • Zölls S, Tantipolphan R, Wiggenhorn M, Winter G, Jiskoot W, Friess W, Hawe A (2012) Particles in therapeutic protein formulations, part 1: overview of analytical methods. J Pharm Sci 101:914–935

    Article  PubMed  Google Scholar 

  • Zou T, Oukacine F, Le Saux T, Cottet H (2010) Neutral coatings for the study of polycation/multicharged anion interactions by capillary electrophoresis: application to dendrigraft poly-L-lysines with negatively multicharged molecules. Anal Chem 82:7362–7368

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen, 2100, Denmark

    Jesper Østergaard, Susan W. Larsen & Henrik Jensen

Authors
  1. Jesper Østergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan W. Larsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henrik Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henrik Jensen .

Editor information

Editors and Affiliations

  1. Bioneer: FARMA Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Anette Müllertz

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, Seychelles

    Yvonne Perrie

  3. Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Thomas Rades

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Controlled Release Society

About this chapter

Cite this chapter

Østergaard, J., Larsen, S.W., Jensen, H. (2016). Capillary-Based Techniques for Physical-Chemical Characterization of Drug Substances and Drug Delivery Systems. In: Müllertz, A., Perrie, Y., Rades, T. (eds) Analytical Techniques in the Pharmaceutical Sciences. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-4029-5_14

Download citation

Publish with us

Policies and ethics

Search

Navigation