CLSM As Quantitative Method to Determine the Size of Drug Crystals in a Solid Dispersion

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2011 May 25

PMID 21607777

Citations 3

Authors

Hans de Waard

Martin J T Hessels

Maarten Boon

Klaas A Sjollema

Wouter L J Hinrichs

Anko C Eissens

Henderik W Frijlink

Affiliations

Soon will be listed here.

Abstract

Purpose: To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion.

Methods: Crystals of the autofluorescent drug dipyridamole were incorporated in a matrix of crystalline mannitol by physical mixing or freeze-drying. Laser diffraction analysis and dissolution testing were used to validate the particle size that was found by CLSM.

Results: The particle size of the pure drug as determined by laser diffraction and CLSM were similar (D(50) of approximately 22 μm). CLSM showed that the dipyridamole crystals in the crystalline dispersion obtained by freeze-drying of less concentrated solutions were of sub-micron size (0.7 μm), whereas the crystals obtained by freeze-drying of more concentrated solutions were larger (1.3 μm). This trend in drug crystal size was in agreement with the dissolution behavior of the tablets prepared from these products.

Conclusion: CLSM is a useful technique to determine the particle size in a powder mixture. Furthermore, CLSM can be used to determine the drug crystal size over a broad size distribution. A limitation of the method is that the drug should be autofluorescent.

Citing Articles

Computational Support to Explore Ternary Solid Dispersions of Challenging Drugs Using Coformer and Hydroxypropyl Cellulose.

Niederquell A, Herzig S, Schonenberger M, Stoyanov E, Kuentz M Mol Pharm. 2024; 21(11):5619-5631.

PMID: 39388157 PMC: 11539070. DOI: 10.1021/acs.molpharmaceut.4c00592.

The Use of Global Sensitivity Analysis to Assess the Oral Absorption of Weakly Basic Compounds: A Case Example of Dipyridamole.

Kesharwani S, Louit G, Ibrahim F Pharm Res. 2024; 41(5):877-890.

PMID: 38538971 DOI: 10.1007/s11095-024-03688-0.

Multi-walled carbon nanotube-based systems for improving the controlled release of insoluble drug dipyridamole.

Zhu W, Huang H, Dong Y, Han C, Sui X, Jian B Exp Ther Med. 2019; 17(6):4610-4616.

PMID: 31105789 PMC: 6507520. DOI: 10.3892/etm.2019.7510.

References

Wu W, Nancollas G . Determination of interfacial tension from crystallization and dissolution data: a comparison with other methods. Adv Colloid Interface Sci. 2000; 79(2-3):229-79. DOI: 10.1016/s0001-8686(98)00072-4. View

Verma S, Gokhale R, Burgess D . A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm. 2009; 380(1-2):216-22. DOI: 10.1016/j.ijpharm.2009.07.005. View

Driscoll D, Etzler F, Barber T, Nehne J, Niemann W, Bistrian B . Physicochemical assessments of parenteral lipid emulsions: light obscuration versus laser diffraction. Int J Pharm. 2001; 219(1-2):21-37. DOI: 10.1016/s0378-5173(01)00626-3. View

Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M . In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol. J Control Release. 2008; 130(1):29-37. DOI: 10.1016/j.jconrel.2008.05.013. View

Hu J, Johnston K, Williams 3rd R . Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev Ind Pharm. 2004; 30(3):233-45. DOI: 10.1081/ddc-120030422. View

Amidon G, Lennernas H, Shah V, Crison J . A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995; 12(3):413-20. DOI: 10.1023/a:1016212804288. View

Iuliano L, Piccheri C, Coppola I, Pratico D, Micheletta F, Violi F . Fluorescence quenching of dipyridamole associated to peroxyl radical scavenging: a versatile probe to measure the chain breaking antioxidant activity of biomolecules. Biochim Biophys Acta. 2000; 1474(2):177-82. DOI: 10.1016/s0304-4165(00)00017-9. View

Bugay D . Characterization of the solid-state: spectroscopic techniques. Adv Drug Deliv Rev. 2001; 48(1):43-65. DOI: 10.1016/s0169-409x(01)00101-6. View

Kostewicz E, Brauns U, Becker R, Dressman J . Forecasting the oral absorption behavior of poorly soluble weak bases using solubility and dissolution studies in biorelevant media. Pharm Res. 2002; 19(3):345-9. DOI: 10.1023/a:1014407421366. View

10.

Doub W, Adams W, Spencer J, Buhse L, Nelson M, Treado P . Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension nasal spray formulations: a progress report. Pharm Res. 2007; 24(5):934-45. DOI: 10.1007/s11095-006-9211-2. View

11.

Patterson J, James M, Forster A, Lancaster R, Butler J, Rades T . The influence of thermal and mechanical preparative techniques on the amorphous state of four poorly soluble compounds. J Pharm Sci. 2005; 94(9):1998-2012. DOI: 10.1002/jps.20424. View

12.

Burger A, Henck J, Hetz S, Rollinger J, Weissnicht A, Stottner H . Energy/temperature diagram and compression behavior of the polymorphs of D-mannitol. J Pharm Sci. 2000; 89(4):457-68. DOI: 10.1002/(SICI)1520-6017(200004)89:4<457::AID-JPS3>3.0.CO;2-G. View

13.

Hou D, Xie C, Huang K, Zhu C . The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials. 2003; 24(10):1781-5. DOI: 10.1016/s0142-9612(02)00578-1. View

14.

Lipinski C, Lombardo F, Dominy B, Feeney P . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1-3):3-26. DOI: 10.1016/s0169-409x(00)00129-0. View

15.

de Waard H, Beer T, Hinrichs W, Vervaet C, Remon J, Frijlink H . Controlled crystallization of the lipophilic drug fenofibrate during freeze-drying: elucidation of the mechanism by in-line Raman spectroscopy. AAPS J. 2010; 12(4):569-75. PMC: 2976986. DOI: 10.1208/s12248-010-9215-z. View

16.

de Waard H, Hinrichs W, Frijlink H . A novel bottom-up process to produce drug nanocrystals: controlled crystallization during freeze-drying. J Control Release. 2008; 128(2):179-83. DOI: 10.1016/j.jconrel.2008.03.002. View

17.

Lobenberg R, Amidon G . Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm. 2000; 50(1):3-12. DOI: 10.1016/s0939-6411(00)00091-6. View

18.

Pygall S, Whetstone J, Timmins P, Melia C . Pharmaceutical applications of confocal laser scanning microscopy: the physical characterisation of pharmaceutical systems. Adv Drug Deliv Rev. 2007; 59(14):1434-52. DOI: 10.1016/j.addr.2007.06.018. View

19.

Keck C, Muller R . Size analysis of submicron particles by laser diffractometry--90% of the published measurements are false. Int J Pharm. 2008; 355(1-2):150-63. DOI: 10.1016/j.ijpharm.2007.12.004. View

20.

Moschwitzer J, Achleitner G, Pomper H, Muller R . Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology. Eur J Pharm Biopharm. 2004; 58(3):615-9. DOI: 10.1016/j.ejpb.2004.03.022. View