Abstract
Particles may be found in a wide range of topical pharmaceutical products, whether as active substances, as functional excipients, or as a constituent part of the drug product, as in the case of emulsion droplets. Formulation of a drug substance as solid particulates introduces a dependence on the dissolution of the drug substance to exert its therapeutic benefit, but at the same time offers the possibility of more sustained drug delivery to the target tissue than may be obtained from a solution formulation. Particles may be employed as emulsifiers (Pickering emulsions) and as thickening agents in gel formulations. Finally, particles may be emulsion droplets in cream or lotion formulations, which usually contain one or more active ingredients dissolved in the dispersed phase. In all of these applications, various attributes of the solid particles may be critical to the functionality of the formulation. These attributes, and the principal techniques used for characterizing particulates for these purposes, are described in this chapter. Also reviewed are the unit operations particularly associated with the manufacture of such products, including mixing, material incorporation and size reduction.
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Notes
- 1.
In this book the symbol D is used for particle size. E.g. to number-based distributions a (second) subscript 0 is given; the mean size is expressed as 〈D1;0〉 and the median size as D50,0; to volume-based distributions a (second) subscript 3 is given; the mean size is expressed as 〈D4;3〉, the median size as D50,3.
- 2.
D10,0, D50,0 and D90,0 are used as symbols for the 10th, 50th and 90th percentile sizes of a number-based distribution, D10,3, D50,3 and D90,3 as the symbols for the 10th, 50th and 90th percentile sizes of a volume-based distribution.
References
Barua S, Mitragotri S (2014) Challenges associated with penetration of nanoparticles across cell and tissue barriers: a review of current status and future prospects. Nano Today 9:223–243
Block LH (2002) Non parenteral liquids and semisolids. In: Levin M (ed) Pharmaceutical scale up. Marcel Dekker Inc., New York
Chen S, Øye G, Sjöblom J (2005) Rheological properties of silica particle suspensions in mineral oil. J Dispers Sci Tech 26:791–798
Dinsmore AD, Hsu MF, Nikolaides MG, Marquez M, Bausch AR, Weitz DA (2002) Colloidosomes: selectively permeable capsules composed of colloidal particles. Science 298:1006–1009
Einstein A (1911) Berichtigung zu meiner arbeit: eine neue bestimmung der moleküldimensionen. Ann Phys 339:591–592
Fairhurst D (2014) An overview of physical (particulate) sunscreens. In: Merkus HG, Meesters GMH (eds) Particulate products: tailoring properties for optimal performance. Springer, Netherlands
Farris RJ (1968) Prediction of the viscosity of multimodal suspensions from unimodal viscosity data. Trans Soc Rheol 12:281–301
Frelichowska J, Bolzinger M-A, Pelletier J, Valour J-P, Chevalier Y (2009) Topical delivery of lipophilic drugs from o/w Pickering emulsions. Int J Pharm 371:56–63
Frelichowska J, Bolzinger M-A, Valour J-P, Mouaziz H, Pelletier J, Chevalier Y (2009) Pickering w/o emulsions: drug release and topical delivery. Int J Pharm 368:7–15
Ghate D, Edelhauser HF (2006) Ocular drug delivery. Expert Opin Drug Deliv 3:275–287
Goupale DC, Rajkapoor B (2011) Evaluation of physical stability of oleogels containing diclofenac diethylamine. Res J Pharm Biol Chem Sci 2:92–99
Iacocca RG, Burcham CL, Hilden LR (2010) Particle engineering: a strategy for establishing drug substance physical property specifications during small molecule development. J Pharm Sci 99:51–75
International Conference on Harmonization (2010) Analytical sieving general chapter, Q4B annex 12. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q4B_Annex_12/Step4/Q4B_Annex_12_Step_4.pdf
Jun C (2001) Improved paste formulations. International Patent Application WO2001060409
Kassem MA, Abdel Rahman AA, Ghorab MM, Ahmed MB, Khalil RM (2007) Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 340:126–133
Kennedy JRM, Kent KE, Brown JR (2015) Rheology of dispersions of xanthan gum, locust bean gum and mixed biopolymer gel with silicon dioxide nanoparticles. Mat Sci Eng C 48:347–353
Lu Z, Fassihi R (2015) Influence of colloidal silicon dioxide on gel strength, robustness, and adhesive properties of diclofenac gel formulation for topical application. AAPS PharmSciTech 16:636–644
Malloy A, Carr B (2006) Nanoparticle tracking analysis—the Halo™ system. Part Part Syst Charact 23:197–204
Manoharan C, Basarkar A, Singh J (2010) Various pharmaceutical disperse systems. In: Kulshreshtha AK, Singh ON, Wall GM (eds) Pharmaceutical suspensions: from formulation development to manufacturing. Springer, New York
Marku D, Wahlgren M, Rayner M, Sjöö M, Timgren A (2012) Characterization of starch Pickering emulsions for potential applications in topical formulations. Int J Pharm 428:1–7
Mathias NR, Hussain MA (2010) Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J Pharm Sci 99:1–20
Merkus HG (2009) Particle size measurements: fundamentals, practice quality. Springer, Netherlands
Merkus HG (2014) Basic information for design of particulate products. In: Merkus HG, Meesters GMH (eds) Particulate products: tailoring properties for optimal performance. Springer, Netherlands
Merkus HG, Meesters GMH (eds) (2014) Particulate products: tailoring properties for optimal performance. Springer, Netherlands
Michniak-Kohn BB, Wertz PW, Al-Khalili M, Meidan VM (2005) Skin: physiology and penetration pathways. In: Rosen MR (ed) Delivery system handbook for personal care and cosmetic products. William Andrew Publishing, Norwich, NY
Murthy SN, Shivakumar HN (2009) Topical and transdermal drug delivery. In: Kulkarni VS (ed) Handbook of non-invasive drug delivery systems: science and technology. William Andrew Publishing, Oxford
Newman MD, Stotland M, Ellis JI (2009) The safety of nanosized particles in titanium dioxide and zinc oxide based sunscreens. J Am Acad Dermatol 61:685–692
Oh M-H, So J-H, Yang S-M (1999) Rheological evidence for the silica-mediated gelation of xanthan gum. J Coll Interfac Sci 216:320–328
Oliveira F, Monteiro SR, Barros-Timmons A, Lopes-da-Silva JA (2010) Weak-gel formation in dispersions of silica particles in a matrix of a non-ionic polysaccharide: Structure and rheological characterization. Carbohyd Polym 82:1219–1227
Pashkovski EE, Masters JG, Mehreteab A (2003) Viscoelastic scaling of colloidal gels in polymer solutions. Langmuir 19:3589–3595
Pathak Y, Thassu D (2010) Scale up and technology transfer of pharmaceutical suspensions. In: Kulshreshtha AK, Singh ON, Wall GM (eds) Pharmaceutical suspensions: from formulation development to manufacturing. Springer, New York
Pickering SU (1907) Emulsions. J Chem Soc 91:2001–2021
Ramsden W (1903) Separation of solids in the surface-layers of solutions and suspensions. Proc R Soc London 72:156–164
Ranade VV, Cannon JB (2011) Transmucosal and ocular drug delivery. In: Drug delivery systems, 3rd ed. CRC Press, Boca Raton
Rawle AF (2010) Analytical tools for suspension characterization. In: Kulshreshtha AK, Singh ON, Wall GM (eds) Pharmaceutical suspensions, from formulation development to manufacturing. Springer, New York
Schroën K, Berton-Carabin CC (2016) Emulsification: established and future technologies. In: Merkus HG, Meesters GMH (eds) Production, handling and characterization of particulate materials. Springer, Netherlands
Schulman JH, Leja J (1954) Control of contact angles at the oil-water-solid interfaces; emulsions stabilized by solid particles (BaSO4). Trans Faraday Soc 50:598–605
TGA OTC Medicines Section (2009) A review of the scientific literature on the safety of nanoparticulate titanium dioxide or zinc oxide in sunscreens. https://www.tga.gov.au/sites/default/files/sunscreens-nanoparticles-2009.pdf. Accessed 27 Feb 2017
Trompette JL, Charnay C, Partyka S (1998) Storage stability and rheological behavior of talc-polyacrylylglycinamide gelified suspensions. Langmuir 14:4475–4481
van Duynhoven JPM, Maillet B, Schell J, Tronquet M, Goudappel G-JW, Trezza E, Bulbarello A, van Dusschoten D (2007) A rapid benchtop NMR method for determination of droplet size distributions in food emulsions. Eur J Lipid Sci Technol 109:1095–1103
Vermeir L, Sabatino P, Balcaen M, Declerck A, Dewettinck K, Martins JC, Van der Meeren P (2016) Effect of molecular exchange on water droplet size analysis in W/O emulsions as determined by diffusion NMR. J Coll Interfac Sci 463:128–136
Zhang Q, Archer LA (2004) Optical polarimetry and mechanical rheometry of poly(ethylene oxide)-silica dispersions. Macromol 37:1928–1936
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Harris, D. (2018). Particulates in Semi-Solid Pharmaceutical Products. In: Merkus, H., Meesters, G., Oostra, W. (eds) Particles and Nanoparticles in Pharmaceutical Products. AAPS Advances in the Pharmaceutical Sciences Series, vol 29. Springer, Cham. https://doi.org/10.1007/978-3-319-94174-5_12
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