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Evaluation of the resistance of a geopolymer-based drug delivery system to tampering
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Material in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Material in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in medicine)
2014 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 465, no 1-2, 169-174 p.Article in journal (Refereed) Published
Abstract [en]

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users.

Place, publisher, year, edition, pages
2014. Vol. 465, no 1-2, 169-174 p.
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-219255DOI: 10.1016/j.ijpharm.2014.02.029ISI: 000333675100022OAI: oai:DiVA.org:uu-219255DiVA: diva2:698822
Funder
Swedish Research Council
Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Geopolymer-based drug formulations for oral delivery of opioids
Open this publication in new window or tab >>Geopolymer-based drug formulations for oral delivery of opioids
2014 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Opioid therapy for chronic pain generally use controlled release formulations to deliver analgesic drugs around-the-clock. Controlled release dosage forms can enlarge the therapeutic effect by controlling the rate and site of release. However, with high drug content, opioid formulations are easily targeted for non-medical use. With the increasing concern of opioid abuse, tamper-resistance becomes an important attribute for opioid controlled-release dosage forms. Geopolymers have been studied as drug carrier for opioids to improve the tamper-resistance but there are still some issues, such as curing condition and fast drug release in acid, have not been studied in detail yet. This thesis focuses on the optimization and evaluation of the geopolymer-based formulation on its controlled-release and tamper-resistance properties with the aim of achieving optimal therapeutic outcomes and reducing abuse potential.

In this work, we showed some further improvement and evaluations on geopolymer-based drug formulations. The mechanical strength and porosity of geopolymers could be influenced by the curing conditions: high humidity for at least 48 hours could improve its mechanical strength, but elevated temperature only accelerated the geopolymerization but promoted water evaporation, leading to shrinkage and crack formation. Incorporating pH-sensitive organic polymers could improve the acid resistance of geopolymer formulation and thus reduce the risk of dose dumping. Comparing to a commercial opioid tablet, the geopolymer matrix have higher mechanical strength and could offer better resistance against physical manipulation and extraction under heating. The results provided solid experimental support on the potential for geopolymer as matrix for oral opioid delivery systems.

Place, publisher, year, edition, pages
Uppsala: Uppsala University, Department of Engineering Sciences, 2014
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-219259 (URN)
Presentation
2014-03-14, 13:28 (English)
Supervisors
Funder
Swedish Research Council
Available from: 2014-02-27 Created: 2014-02-25 Last updated: 2014-07-24Bibliographically approved
2. Ceramic Materials for Administration of Potent Drugs
Open this publication in new window or tab >>Ceramic Materials for Administration of Potent Drugs
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aimed to investigate and document the potential of applying ceramics in two specific drug delivery applications: tamper-resistant opioid formulations and transdermal enhancement protrusions.

Geopolymers were developed into the matrix for a tamper-resistant formulation, aiming to protect drug substances from non-medical abuse. The synthesis conditions and excipients composition of the geopolymer-based formulation were modified in this work to facilitate a stable and extended drug delivery. Results showed that 37ºC 100% humidity for 48 hours were applicable conditions to obtain geopolymer with suitable mechanical strength and porosity. Moreover, it was found that the integration of poly(methyl acrylate) into the geopolymer-based formulation could reduce the drug release at low pH and, meanwhile, maintain the mechanical strength. Therefore, the geopolymer-based drug formulations concluded from these studies were applied in oral and transdermal delivery systems. Evidence of the tamper-resistance of geopolymer-based oral and transdermal formulations was documented and compared to the corresponding commercial opioid formulations. The results provided experimental support for the positive effects of geopolymers as drug carriers for the tamper-resistance of oral and transdermal delivery systems.

Self-setting bioceramics, calcium phosphate and calcium sulfate were fabricated into transdermal enhancement protrusions in this work for the first time. Results showed that, under mild conditions, both bioceramics could form pyramid-shaped needles in the micron size. The drug release from these needles could be controlled by the bulk surface area, porosity and degradation of the bioceramics. An in vitro insertion test showed that the bioceramic microneedles had enough mechanical strength to insert into skin. Further optimization on the geometry of needles and the substrate material was also performed. The higher aspect-ratio needles with a flexible and self-swellable substrate could release most of the drug content within 4 hours and could penetrate through the stratum corneum by manual insertion. This study explored the potential application of bioceramics in transdermal enhancement protrusions and showed promising indication of their future developments.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1235
Keyword
Tamper-resistance, Oral formulation, Transdermal formulation, Biomaterials, Microneedles
National Category
Biomaterials Science Ceramics
Identifiers
urn:nbn:se:uu:diva-245031 (URN)978-91-554-9188-8 (ISBN)
Public defence
2015-04-28, Polhemssalen, Lägerhyddsvägen 2, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2015-04-07 Created: 2015-02-24 Last updated: 2015-04-17

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Cai, BingEngqvist, HåkanBredenberg, Susanne

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