Rades, T

Zeitler, JA

PubMed

Apollo (Cambridge)

EDITORIALI n te rdependence o f Dosage Form Mic ro s t ruc tu reand Per fo rmanceJ. Axel Zeitler1 & Thomas Rades2Received: 26 February 2017 /Accepted: 27 February 2017 /Published online: 15 March 2017# The Author(s) 2017Our understanding of quality in pharmaceutical productionhas evolved significantly over the past decade. The quality-by-design initiative has proved to be a catalyst for those workingin the pharmaceutical science community to reconsiderestablished quality testing protocols and focus research onthe effect of processing steps on the quality of dosage forms.With clear progress being made in the implementation ofcontinuous processing into industrial practice there has alsobeen a realisation that pharmaceutical engineering and mate-rials sciences need to be better integrated into existing prac-tice. Traditionally, the pharmaceutical development process,the regulatory process and the testing requirements outlinedin the pharmacopeias place a strong emphasis on chemicalpurity and drug content as well as the safety and efficacy ofthe medicines. It is this context that has dominated the per-ception of quality in our community and with which we are allfamiliar. However, it has become increasingly clear that inorder to achieve stable manufacturing processes that resultin consistent product quality it is now critical to understandthe physical characteristics of drug products in far greaterdetail than is currently the status quo. The microstructure, thatis the physical structure at microscopic scale, determines asignificant range of critical quality attributes of a dosage form,given their nature as complex multi-particulate mixtures ofdrug and excipients. Thus there is a continuing need for betterfundamental understanding of the interdependence of micro-structure and product quality. The lack of sufficiently sensitivemeasurement techniques and the limited awareness of the roleof microstructure for pharmaceutical quality present signifi-cant barriers that restrict the production of drug products ofthe highest quality and within sustainable and economic pro-cesses. It is this lacuna that the current themed issue aims toaddress, through raising awareness, educating and highlight-ing recent developments that the editors believe have the po-tential for having a significant impact on the field.In contrast to the chemical structure of the drug and excip-ients, the microstructure of the dosage form is defined duringthe manufacturing process. The same chemical can exhibit awide range of performance characteristics depending on itsphysical structure, much like crystalline polymorphs, from achemical point of view, are identical but will have differentsolubilities. The role of the microstructure is well illustrated bythe example of dissolution testing of immediate release tabletsthat contain a BCS class I drug. The compendial tests typicallyrequire a high fraction of the drug, e.g. 75 or 80%, to bereleased and dissolved from the dosage form in time periodsof 30–45 min. However, closer inspection of the drug releaseprofiles shows that in the vast majority of cases the drug releasecharacteristics vary enormously in the early stages of the test(e.g. at times <15 min) and the variability of the drug concen-tration only gradually decreases to the ‘acceptable’ thresholdclose to the defined testing point as specified in the respectivecompendial method. This variation in release characteristics isdirectly linked to the disintegration process, which itself isdetermined by the dosage form microstructure. The reviewby D. Markl and J.A. Zeitler outlines the fundamental originsof this link and how a lack of meaningful testing protocols has* J. Axel Zeitlerjaz22@cam.ac.ukThomas Radesthomas.rades@sund.ku.dk1 Department of Chemical Engineering and Biotechnology, University ofCambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK2 Department of Pharmacy, University of Copenhagen, Universitetsparken2, 2100 Copenhagen, DenmarkPharm Res (2017) 34:887–889DOI 10.1007/s11095-017-2137-zresulted in a lack of appreciation of the connection betweenphysical structure and the quality of the dosage form.C.C. Sun further develops the argument by highlightinghow microstructure not only determines the disintegration ofthe dosage form but also its mechanical properties that can beachieved by powder compaction. This is of critical importanceboth in terms of designing the optimal particle characteristicsduring formulation development and selecting the most ap-propriate processing route and conditions. The interplay be-tween process parameters, the microstructure and theresulting product performance are critical for defining andevolving the design space during process development andscale up. Even though the formulation is the same, theresulting dosage form can behave very differently. In otherwords, the microstructure is the key characteristic to under-stand prior to rational design.The review by Y. Sun and J. Østergaard complements thisdiscussion by highlighting opportunities that can be realisedby replacing traditional UV spectroscopy with modern UVimaging methods for the analysis of the dissolution process.This methodology makes it possible to understand better theinteraction between drug and excipients within the formula-tion and how this can result in different structures (for examplein gels, which strongly affect the drug release characteristics ofthe dosage form). The study by A. Hu et al. highlights thisthesis further by providing more in-depth insights into thephysicochemical changes that take place within the dosageform during dissolution from a matrix system. Using quanti-tative magnetic resonance imaging (MRI) experiments andconfocal microscopy it is possible to rationalise the structuralchanges in hydrophilic polymer matrices during drug release.It also sheds light on our understanding of how structuralchanges affect the mass transport of dissolution liquid intothe gel structure and drug out of the dosage form.An attractive and increasingly popular practice in solidstate formulation development is using amorphous drug toincrease the bioavailability of poorly soluble drug compounds.But, given that amorphous drug substances are inherentlymetastable and will eventually convert into a less soluble crys-talline form, it is of critical importance to be able to detectcrystalline material with sufficient sensitivity and to under-stand what triggers the crystallisation process. At present, atypical quality control method will attempt to measure thetotal crystallinity of the entire sample. This is problematicfor a number of reasons. Besides the fact that most measure-ments do not sample the entire volume of a dosage form thereis no technique that can reliably detect trace amounts of crys-talline material in a bulk sample with sufficient sensitivity.However, even a trace of crystalline material that is spatiallyconfined to a small area of the dosage form can act as anucleation site from which crystallisation can take place rap-idly and throughout the dosage form. The contribution byP.T. Mah et al. provides a fascinating insight into the spatialdistribution of crystallinity induced by compression of anamorphous drug substance. The authors were able to demon-strate that, while the presence of excipients did affect the rateof surface crystallisation, it was not able to preventcrystallisation upon tableting. It is important to highlight herethat a physical mixture of drug/excipient was used for thisstudy rather than a solid dispersion. The measurements werepreformed using a combination of well-established physicalsurface characterisation techniques such as scanning electronmicroscopy and attenuated total reflection (ATR) infraredspectroscopy as well as sum frequency generation microscopy(a highly sensitive optical measurement technique that canreliably detect crystallinity of non-centrosymmetric samples).M. Alhijjaj et al. use the example of an amorphoussolid dispersion prepared using a hot melt extrusion pro-cess to study the stability of the amorphous drug withinthe polymer matrix. This combination of formulationand process is one of the preferred industrial platformsfor realising amorphous dosage forms. By using advancedthermal analysis rout ines combined with X-raymicrotomography the authors were able to confirm thatthe crystallisation process is preceded by a phase separa-tion process and the crystal nuclei clearly form fromwithin in the drug domains. The combination of thermalcharacterisation and spatial resolution of the process pro-vides a unique insight into how the physical structurepresets the conditions for the crystallisation process.Following the theme of amorphous stabil ity, K.Punčochová et al. further emphasise how different imag-ing techniques based on vibrational spectroscopy, as wellas MRI, can be used to analyse the drug release processfrom a solid dispersion formulation. Even if the formula-tion is stable and the drug molecules are successfully keptin their amorphous state, the solubility advantage can belost during the drug release process in the patient’sgastro-intestinal tract. This complex process includesmass transport of dissolution liquid into the matrix,swelling, dissolution and supersaturation as well as masstransport out of the drug/polymer matrix. The authorsshow how it is possible to detect the onset of unwantedcrystallisation using the imaging approach during formu-lation development and how this information can beused to develop a systematic strategy for it.The next two contributions turn the focus of this themeissue from the formulation and its microstructure at themolecular and domain level to the next larger length scale:the inter-particle scale in granular materials and its effecton tablet structure following compaction. S. van den Banand D.J. Goodwin describe the development of a highshear wet granulation process to achieve granules with awide range of densities. This work is a prime example of aquality-by-design driven process development and how thiscan be realised at production scale. Clearly the density of888 Axel Zeitler and Radesthe granules is of critical importance and largely accords tothe microstructure in the subsequent compaction process.Using the tablets produced from these granules as an ex-ample, D. Markl et al. show how the bulk porosity of atablet can be measured non-destructively and withoutany prior sample preparation using terahertz spectroscopy.The authors argue that porosity is a key critical qualityattribute for immediate release tablets, and one that is farbetter suited to predict disintegration of dissolution char-acteristics than, for example, tablet hardness.In the final two articles, attention shifts away from tradi-tional solid dosage forms to emerging drug delivery technolo-gies based on 3D printing.M. Edinger et al. introduce a proof-of-concept study of how Raman spectroscopy and imagingmethods can be used in inkjet-printed drug delivery systemsto resolve the drug distribution within the dosage form.Finally, with the example of a set of 3D printed dosage formsprepared using the fused deposition modelling technique, D.Markl et al. demonstrate the significant discrepancy in inter-nal structure between the computer aided design models andthe actual structures that can be realised using such technolo-gy. Whilst there is considerable enthusiasm in the pharmaceu-tical community to take advantage of the exciting opportuni-ties in 3D printing a meaningful discussion regarding theunique requirements to define dosage form quality is yet totake place and, as demonstrated by this work, microstructurewill have to be a central concern.That new dosage forms and processing techniques requirenew analytical technologies as meaningful descriptors of qual-ity is a key message expressed by all contributors to this issue.The tools currently described or required by thepharmacopoeiae are no longer fit for purpose as, typically,they do not allow us to quantify the role or effect of the mi-crostructure for the performance of the formulation or dosageform. There needs to be a shared motivation in pharmaceu-tical development and engineering to develop the tools thatthe pharmaceutical industry need in order to meet two keychallenges of our time: improved drug product quality and ashift to continuous manufacturing. The ability to rationallydesign, reproduce and reliably detect a well-defined micro-structure will be essential to these endeavours, not least toimplement meaningful process analytical technologies andcontrol strategies into the manufacturing process.OpenAccessThis article is distributed under the terms of theCreative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which per-mits unrestricted use, distribution, and reproduction in anymedium, provided you give appropriate credit to the originalauthor(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made.Dr Axel Zeitler FRSC isR e a d e r i n C h em i c a lE n g i n e e r i n g a t t h eDepartment of ChemicalE n g i n e e r i n g a n dBiotechnology, Universityof Cambridge, where hehas l ed the Teraher tzApplications Group since2010. Prior to this DrZeitler completed his PhDwith Professor ThomasRades at the School of Pharmacy, University of Otago,New Zealand and held research posi t ions at theCavendish Laboratory, University of Cambridge, UK andTeraView Ltd. Dr Zeitler is the recipient of the 2016Science Award by the Royal Pharmaceutical Society. Heis a Fellow of Gonville and Caius College, Cambridge.Professor Dr. Dr. h.c.Thomas Rades is theR e s e a r c h C h a i r i nPharmaceutical Design andDrug De l i v e r y in theDepartment of Pharmacy,University of Copenhagen(since 2012). In 1994 he re-ceived a PhD from theTechnical University ofBraunschweig, Germany forhis work on thermotropicand lyotropic liquid crystalline drugs. After working as aResearch Scientist in the Preclinical Development andFormulation at F. Hoffmann-La Roche in Basel, Switzerland,he became a Senior Lecturer in Pharmaceutical Sciences atOtago in 1999 and from 2003 to 2012 held the Chair inPharmaceutical Sciences in Otago. Professor Rades has devel-oped an international reputation for his research in drug deliveryand physical characterisation of drugs. Professor Rades is anEditor of the Journal of Pharmaceutical Sciences and theEuropean Journal of Pharmaceutics and Biopharmaceutics. Heholds an honorary doctorate of Åbo Akademi University,Finland, a visiting professorship at the Department of Medicineat the University of Adelaide, Australia and an honorary profes-sorship at the University of Otago, New Zealand. He is anEminent Fellow of the Academy of Pharmaceutical Sciences, aFellow of theNewZealand Institute of Chemistry and amemberof the College of Fellows of the Controlled Release Society.Interdependence of Dosage Form Microstructure and Performance 889

Interdependence of Dosage Form Microstructure and Performance

J. Axel Zeitler

Thomas Rades

Crossref

Pharmaceutical Research

Axel Zeitler, J

Rades, Thomas

Copenhagen University Research Information System

u n i ve r s i t y  o f  co pe n h ag e n  Københavns UniversitetInterdependence of Dosage Form Microstructure and PerformanceAxel Zeitler, J; Rades, ThomasPublished in:Pharmaceutical ResearchDOI:10.1007/s11095-017-2137-zPublication date:2017Document versionPublisher's PDF, also known as Version of recordDocument license:CC BYCitation for published version (APA):Axel Zeitler, J., & Rades, T. (2017). Interdependence of Dosage Form Microstructure and Performance.Pharmaceutical Research, 34(5), 887-889. https://doi.org/10.1007/s11095-017-2137-zDownload date: 03. Feb. 2020EDITORIALI n te rdependence o f Dosage Form Mic ro s t ruc tu reand Per fo rmanceJ. Axel Zeitler1 & Thomas Rades2Received: 26 February 2017 /Accepted: 27 February 2017 /Published online: 15 March 2017# The Author(s) 2017Our understanding of quality in pharmaceutical productionhas evolved significantly over the past decade. The quality-by-design initiative has proved to be a catalyst for those workingin the pharmaceutical science community to reconsiderestablished quality testing protocols and focus research onthe effect of processing steps on the quality of dosage forms.With clear progress being made in the implementation ofcontinuous processing into industrial practice there has alsobeen a realisation that pharmaceutical engineering and mate-rials sciences need to be better integrated into existing prac-tice. Traditionally, the pharmaceutical development process,the regulatory process and the testing requirements outlinedin the pharmacopeias place a strong emphasis on chemicalpurity and drug content as well as the safety and efficacy ofthe medicines. It is this context that has dominated the per-ception of quality in our community and with which we are allfamiliar. However, it has become increasingly clear that inorder to achieve stable manufacturing processes that resultin consistent product quality it is now critical to understandthe physical characteristics of drug products in far greaterdetail than is currently the status quo. The microstructure, thatis the physical structure at microscopic scale, determines asignificant range of critical quality attributes of a dosage form,given their nature as complex multi-particulate mixtures ofdrug and excipients. Thus there is a continuing need for betterfundamental understanding of the interdependence of micro-structure and product quality. The lack of sufficiently sensitivemeasurement techniques and the limited awareness of the roleof microstructure for pharmaceutical quality present signifi-cant barriers that restrict the production of drug products ofthe highest quality and within sustainable and economic pro-cesses. It is this lacuna that the current themed issue aims toaddress, through raising awareness, educating and highlight-ing recent developments that the editors believe have the po-tential for having a significant impact on the field.In contrast to the chemical structure of the drug and excip-ients, the microstructure of the dosage form is defined duringthe manufacturing process. The same chemical can exhibit awide range of performance characteristics depending on itsphysical structure, much like crystalline polymorphs, from achemical point of view, are identical but will have differentsolubilities. The role of the microstructure is well illustrated bythe example of dissolution testing of immediate release tabletsthat contain a BCS class I drug. The compendial tests typicallyrequire a high fraction of the drug, e.g. 75 or 80%, to bereleased and dissolved from the dosage form in time periodsof 30–45 min. However, closer inspection of the drug releaseprofiles shows that in the vast majority of cases the drug releasecharacteristics vary enormously in the early stages of the test(e.g. at times <15 min) and the variability of the drug concen-tration only gradually decreases to the ‘acceptable’ thresholdclose to the defined testing point as specified in the respectivecompendial method. This variation in release characteristics isdirectly linked to the disintegration process, which itself isdetermined by the dosage form microstructure. The reviewby D. Markl and J.A. Zeitler outlines the fundamental originsof this link and how a lack of meaningful testing protocols has* J. Axel Zeitlerjaz22@cam.ac.ukThomas Radesthomas.rades@sund.ku.dk1 Department of Chemical Engineering and Biotechnology, University ofCambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK2 Department of Pharmacy, University of Copenhagen, Universitetsparken2, 2100 Copenhagen, DenmarkPharm Res (2017) 34:887–889DOI 10.1007/s11095-017-2137-zresulted in a lack of appreciation of the connection betweenphysical structure and the quality of the dosage form.C.C. Sun further develops the argument by highlightinghow microstructure not only determines the disintegration ofthe dosage form but also its mechanical properties that can beachieved by powder compaction. This is of critical importanceboth in terms of designing the optimal particle characteristicsduring formulation development and selecting the most ap-propriate processing route and conditions. The interplay be-tween process parameters, the microstructure and theresulting product performance are critical for defining andevolving the design space during process development andscale up. Even though the formulation is the same, theresulting dosage form can behave very differently. In otherwords, the microstructure is the key characteristic to under-stand prior to rational design.The review by Y. Sun and J. Østergaard complements thisdiscussion by highlighting opportunities that can be realisedby replacing traditional UV spectroscopy with modern UVimaging methods for the analysis of the dissolution process.This methodology makes it possible to understand better theinteraction between drug and excipients within the formula-tion and how this can result in different structures (for examplein gels, which strongly affect the drug release characteristics ofthe dosage form). The study by A. Hu et al. highlights thisthesis further by providing more in-depth insights into thephysicochemical changes that take place within the dosageform during dissolution from a matrix system. Using quanti-tative magnetic resonance imaging (MRI) experiments andconfocal microscopy it is possible to rationalise the structuralchanges in hydrophilic polymer matrices during drug release.It also sheds light on our understanding of how structuralchanges affect the mass transport of dissolution liquid intothe gel structure and drug out of the dosage form.An attractive and increasingly popular practice in solidstate formulation development is using amorphous drug toincrease the bioavailability of poorly soluble drug compounds.But, given that amorphous drug substances are inherentlymetastable and will eventually convert into a less soluble crys-talline form, it is of critical importance to be able to detectcrystalline material with sufficient sensitivity and to under-stand what triggers the crystallisation process. At present, atypical quality control method will attempt to measure thetotal crystallinity of the entire sample. This is problematicfor a number of reasons. Besides the fact that most measure-ments do not sample the entire volume of a dosage form thereis no technique that can reliably detect trace amounts of crys-talline material in a bulk sample with sufficient sensitivity.However, even a trace of crystalline material that is spatiallyconfined to a small area of the dosage form can act as anucleation site from which crystallisation can take place rap-idly and throughout the dosage form. The contribution byP.T. Mah et al. provides a fascinating insight into the spatialdistribution of crystallinity induced by compression of anamorphous drug substance. The authors were able to demon-strate that, while the presence of excipients did affect the rateof surface crystallisation, it was not able to preventcrystallisation upon tableting. It is important to highlight herethat a physical mixture of drug/excipient was used for thisstudy rather than a solid dispersion. The measurements werepreformed using a combination of well-established physicalsurface characterisation techniques such as scanning electronmicroscopy and attenuated total reflection (ATR) infraredspectroscopy as well as sum frequency generation microscopy(a highly sensitive optical measurement technique that canreliably detect crystallinity of non-centrosymmetric samples).M. Alhijjaj et al. use the example of an amorphoussolid dispersion prepared using a hot melt extrusion pro-cess to study the stability of the amorphous drug withinthe polymer matrix. This combination of formulationand process is one of the preferred industrial platformsfor realising amorphous dosage forms. By using advancedthermal analysis rout ines combined with X-raymicrotomography the authors were able to confirm thatthe crystallisation process is preceded by a phase separa-tion process and the crystal nuclei clearly form fromwithin in the drug domains. The combination of thermalcharacterisation and spatial resolution of the process pro-vides a unique insight into how the physical structurepresets the conditions for the crystallisation process.Following the theme of amorphous stabil ity, K.Punčochová et al. further emphasise how different imag-ing techniques based on vibrational spectroscopy, as wellas MRI, can be used to analyse the drug release processfrom a solid dispersion formulation. Even if the formula-tion is stable and the drug molecules are successfully keptin their amorphous state, the solubility advantage can belost during the drug release process in the patient’sgastro-intestinal tract. This complex process includesmass transport of dissolution liquid into the matrix,swelling, dissolution and supersaturation as well as masstransport out of the drug/polymer matrix. The authorsshow how it is possible to detect the onset of unwantedcrystallisation using the imaging approach during formu-lation development and how this information can beused to develop a systematic strategy for it.The next two contributions turn the focus of this themeissue from the formulation and its microstructure at themolecular and domain level to the next larger length scale:the inter-particle scale in granular materials and its effecton tablet structure following compaction. S. van den Banand D.J. Goodwin describe the development of a highshear wet granulation process to achieve granules with awide range of densities. This work is a prime example of aquality-by-design driven process development and how thiscan be realised at production scale. Clearly the density of888 Axel Zeitler and Radesthe granules is of critical importance and largely accords tothe microstructure in the subsequent compaction process.Using the tablets produced from these granules as an ex-ample, D. Markl et al. show how the bulk porosity of atablet can be measured non-destructively and withoutany prior sample preparation using terahertz spectroscopy.The authors argue that porosity is a key critical qualityattribute for immediate release tablets, and one that is farbetter suited to predict disintegration of dissolution char-acteristics than, for example, tablet hardness.In the final two articles, attention shifts away from tradi-tional solid dosage forms to emerging drug delivery technolo-gies based on 3D printing.M. Edinger et al. introduce a proof-of-concept study of how Raman spectroscopy and imagingmethods can be used in inkjet-printed drug delivery systemsto resolve the drug distribution within the dosage form.Finally, with the example of a set of 3D printed dosage formsprepared using the fused deposition modelling technique, D.Markl et al. demonstrate the significant discrepancy in inter-nal structure between the computer aided design models andthe actual structures that can be realised using such technolo-gy. Whilst there is considerable enthusiasm in the pharmaceu-tical community to take advantage of the exciting opportuni-ties in 3D printing a meaningful discussion regarding theunique requirements to define dosage form quality is yet totake place and, as demonstrated by this work, microstructurewill have to be a central concern.That new dosage forms and processing techniques requirenew analytical technologies as meaningful descriptors of qual-ity is a key message expressed by all contributors to this issue.The tools currently described or required by thepharmacopoeiae are no longer fit for purpose as, typically,they do not allow us to quantify the role or effect of the mi-crostructure for the performance of the formulation or dosageform. There needs to be a shared motivation in pharmaceu-tical development and engineering to develop the tools thatthe pharmaceutical industry need in order to meet two keychallenges of our time: improved drug product quality and ashift to continuous manufacturing. The ability to rationallydesign, reproduce and reliably detect a well-defined micro-structure will be essential to these endeavours, not least toimplement meaningful process analytical technologies andcontrol strategies into the manufacturing process.OpenAccessThis article is distributed under the terms of theCreative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which per-mits unrestricted use, distribution, and reproduction in anymedium, provided you give appropriate credit to the originalauthor(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made.Dr Axel Zeitler FRSC isR e a d e r i n C h em i c a lE n g i n e e r i n g a t t h eDepartment of ChemicalE n g i n e e r i n g a n dBiotechnology, Universityof Cambridge, where hehas l ed the Teraher tzApplications Group since2010. Prior to this DrZeitler completed his PhDwith Professor ThomasRades at the School of Pharmacy, University of Otago,New Zealand and held research posi t ions at theCavendish Laboratory, University of Cambridge, UK andTeraView Ltd. Dr Zeitler is the recipient of the 2016Science Award by the Royal Pharmaceutical Society. Heis a Fellow of Gonville and Caius College, Cambridge.Professor Dr. Dr. h.c.Thomas Rades is theR e s e a r c h C h a i r i nPharmaceutical Design andDrug De l i v e r y in theDepartment of Pharmacy,University of Copenhagen(since 2012). In 1994 he re-ceived a PhD from theTechnical University ofBraunschweig, Germany forhis work on thermotropicand lyotropic liquid crystalline drugs. After working as aResearch Scientist in the Preclinical Development andFormulation at F. Hoffmann-La Roche in Basel, Switzerland,he became a Senior Lecturer in Pharmaceutical Sciences atOtago in 1999 and from 2003 to 2012 held the Chair inPharmaceutical Sciences in Otago. Professor Rades has devel-oped an international reputation for his research in drug deliveryand physical characterisation of drugs. Professor Rades is anEditor of the Journal of Pharmaceutical Sciences and theEuropean Journal of Pharmaceutics and Biopharmaceutics. Heholds an honorary doctorate of Åbo Akademi University,Finland, a visiting professorship at the Department of Medicineat the University of Adelaide, Australia and an honorary profes-sorship at the University of Otago, New Zealand. He is anEminent Fellow of the Academy of Pharmaceutical Sciences, aFellow of theNewZealand Institute of Chemistry and amemberof the College of Fellows of the Controlled Release Society.Interdependence of Dosage Form Microstructure and Performance 889

English

https://www.repository.cam.ac.uk/bitstream/1810/264298/1/Zeitler.pdf

Interdependence of Dosage Form Microstructure and Performance

Abstract

Similar works

Full text

Available Versions

Apollo (Cambridge)

Crossref

Copenhagen University Research Information System