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Badal Tejedor, MariaORCID iD iconorcid.org/0000-0001-5894-7123
Publications (4 of 4) Show all publications
Badal Tejedor, M., Nordgren, N., Schuleit, M., Millqvist-Fureby, A. & Rutland, M. W. (2019). AFM colloidal probe measurements implicate capillary condensation in punch-particle surface interactions during tableting. Paper presented at National Meeting of the American-Chemical-Society (ACS), MAR 31-APR 04, 2019, Orlando, FL. Abstracts of Papers of the American Chemical Society, 257
Open this publication in new window or tab >>AFM colloidal probe measurements implicate capillary condensation in punch-particle surface interactions during tableting
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2019 (English)In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 257Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Manufacturing, Surface and Joining Technology
Identifiers
urn:nbn:se:kth:diva-257614 (URN)000478860504727 ()
Conference
National Meeting of the American-Chemical-Society (ACS), MAR 31-APR 04, 2019, Orlando, FL
Note

QC 20190918

Available from: 2019-09-18 Created: 2019-09-18 Last updated: 2019-09-18Bibliographically approved
Badal Tejedor, M., Pazesh, S., Nordgren, N., Schuleit, M., Rutland, M. W., Alderborn, G. & Millqvist-Fureby, A. (2018). Milling induced amorphisation andrecrystallization of α-lactose monohydrate. International Journal of Pharmaceutics, 537(1-2), 140-147
Open this publication in new window or tab >>Milling induced amorphisation andrecrystallization of α-lactose monohydrate
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2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 537, no 1-2, p. 140-147Article in journal (Refereed) Published
Abstract [en]

Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the alpha-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed alpha-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between un-processed a-lactose, 1 h and 20 h milled lactose and spray dried lactose were detected from SEM and AFM images. Additionally, AFM was used to simultaneously characterize particle surface amorphicity by measuring energy dissipation. Extensive surface amorphicity was detected after 1 h of milling while prolonged milling times showed only a moderate particle surface amorphisation. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1 h milled lactose and a fully amorphous thermal profile for the 20 h milled lactose. The temperature profiles however, were shifted somewhat in the comparison to the amorphous reference, particularly after extended milling, suggesting a different amorphous state compared to the spraydried material. Water loss during milling was measured with TGA, showing lower water content for the lactose amorphized through milling compared to spray dried amorphous lactose. The combined results suggest a surface-bulk propagation of the amorphicity during milling in combination with a different amorphous structural conformation to that of the amorphous spray dried lactose. The hardened surface may be due to either surface crystallization of lactose or to formation of a low-water glass transition.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
tableting, milling, lactose, amorphisation, recrystallization, mechanical properties, atomic force microscopy, differential scanning calorimetry, TGA
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:kth:diva-220332 (URN)10.1016/j.ijpharm.2017.12.021 (DOI)000424263700016 ()29262302 (PubMedID)2-s2.0-85038844261 (Scopus ID)
Note

QC 20171219

Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-02-22Bibliographically approved
Badal Tejedor, M., Nordgren, N., Schuleit, M., Millqvist-Fureby, A. & Rutland, M. W. (2017). AFM Colloidal Probe Measurements Implicate Capillary Condensation in Punch-Particle Surface Interactions during Tableting. Langmuir, 33(46), 13180-13188
Open this publication in new window or tab >>AFM Colloidal Probe Measurements Implicate Capillary Condensation in Punch-Particle Surface Interactions during Tableting
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2017 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, no 46, p. 13180-13188Article in journal (Refereed) Published
Abstract [en]

Adhesion of the powders to the punches is a common issue during tableting. This phenomenon is known as sticking and affects the quality of the manufactured tablets. Defective tablets increase the cost of the manufacturing process. Thus, the ability to predict the tableting performance of the formulation blend before the process is scaled-up is important. The adhesive propensity of the powder to the tableting tools is mostly governed by the surface surface adhesive interactions. Atomic force microscopy (AFM) colloidal probe is a surface characterization technique that allows the measurement of the adhesive interactions between two materials of interest. In this study, AFM steel colloidal probe measurements were performed on ibuprofen, MCC (microcrystalline cellulose), alpha-lactose monohydrate, and spray-dried lactose particles as an approach to modeling the punch particle surface interactions during tableting. The excipients (lactose and MCC) showed constant, small, attractive, and adhesive forces toward the steel surface after a repeated number of contacts. In comparison, ibuprofen displayed a much larger attractive and adhesive interaction increasing over time both in magnitude and in jump-in/jump-out separation distance. The type of interaction acting on the excipient steel interface can be related to a van der Waals force, which is relatively weak and short-ranged. By contrast, the ibuprofen steel interaction is described by a capillary force profile. Even though ibuprofen is not highly hydrophilic, the relatively smooth surfaces of the crystals allow "contact flooding" upon contact with the steel probe. Capillary forces increase because of the "harvesting" of moisture due to the fast condensation kinetics leaving a residual condensate that contributes to increase the interaction force after each consecutive contact. Local asperity contacts on the more hydrophilic surface of the excipients prevent the flooding of the contact zone, and there is no such adhesive effect under the same ambient conditions. The markedly different behavior detected by force measurements clearly shows the sticky and nonsticky propensity of the materials and allows a mechanistic description.

National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-220277 (URN)10.1021/acs.langmuir.7b02189 (DOI)000416498800003 ()29048171 (PubMedID)2-s2.0-85034836128 (Scopus ID)
Note

QC 20180108

Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-01-08Bibliographically approved
Badal Tejedor, M. (2017). Interfacial and material aspects of powders with relevance to pharmaceutical tableting performance. (Doctoral dissertation). Stockholm: KTH Royal Institute of Technology
Open this publication in new window or tab >>Interfacial and material aspects of powders with relevance to pharmaceutical tableting performance
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tablets are the most common forms of drug administration. They are convenient to administer and easy to manufacture. However, problems associated with the adhesion of the powders to the tableting tools are common. This phenomenon is known as sticking and even though it has been well documented and studied, it remains poorly understood. The many factors that contribute to good performance of the powders make the sticking problem difficult to solve.

The goal of this study is to establish a relationship between the properties measured at the nanoscale to the overall tablet mechanical properties, tablet performance and powder pre-processing induced modifications. By using atomic force microscopy (AFM) we aim to develop an analytical method to characterize the mechanical and adhesive properties of the pharmaceutical powders at the nanoscale. Other methodologies such as scanning electron microscopy (SEM), thermal analyses (DSC, TGA) and tablet strength test were also used. The materials used in this study are commonly used excipients, a sticky drug and magnesium stearate (MgSt). Two different approaches offered by AFM were employed: sharp tip imaging and colloidal probe force measurements. Nano-mechanical properties of the materials were evaluated with a sharp tip cantilever showing that higher adhesion correlates with higher tablet cohesion and that both are significantly affected by the presence of MgSt. AFM characterization of the particle surface mechanical properties at the nanoscale was also used to detect the crystallinity and amorphicity levels of the materials. New approaches to presenting such data considering the particle heterogeneity and to track the dynamics of surface recrystallization are revealed. Adhesive interactions between a steel sphere and sticky and non-sticky powders were performed with the colloidal probe technique. Sticky materials presented a higher adhesion against the steel surface, and reveal the mechanism of stickiness.

This work thus contributes to the provision of predictability of the performance of formulations at an early stage of the development process.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. p. 92
Series
TRITA-CHE-Report, ISSN 1654-1081 ; 2017:14
Keywords
atomic force microscopy, excipients, surface characterization, tableting, milling, amorphisation
National Category
Materials Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kth:diva-203125 (URN)978-91-7729-293-7 (ISBN)
Public defence
2017-03-24, F3, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20170315

Available from: 2017-03-15 Created: 2017-03-13 Last updated: 2017-12-18Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-5894-7123

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