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Geopolymer-based drug formulations for oral delivery of opioids
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Material in Medicine)
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: urn:nbn:se:uu:diva-219259OAI: oai:DiVA.org:uu-219259DiVA: diva2:698839
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
List of papers
1. Evaluation of the resistance of a geopolymer-based drug delivery system to tampering
Open this publication in new window or tab >>Evaluation of the resistance of a geopolymer-based drug delivery system to tampering
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.

National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-219255 (URN)10.1016/j.ijpharm.2014.02.029 (DOI)000333675100022 ()
Funder
Swedish Research Council
Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2017-12-05Bibliographically approved
2. The effect of curing conditions on compression strength and porosity of metakaolin-based geopolymers
Open this publication in new window or tab >>The effect of curing conditions on compression strength and porosity of metakaolin-based geopolymers
2013 (English)In: Developments in Strategic Materials and Computational Design IV, John Wiley & Sons, 2013Conference paper, Published paper (Refereed)
Abstract [en]

Geopolymers have been suggested to use as construction, waste treatment and fire proof materials and even drug delivery material due to its excellent mechanical strength, chemical stability and flame resistance. The aim of this study was to investigate the influence of temperature, time and humidity during curing on mechanical strength and porosity of geopolymers.

The geopolymer precursor paste was obtained by mixing metakaolin, waterglass and de-ionized water. The paste was molded into cylindrical rubber moulds (6  12 mm) and cured under different conditions: i.e. temperatures (ambient temperature, 37°C and 90°C), humidity and time (24, 48 and 96 hours). The compressive strength was determined using a universal testing machine. Helium pycnometer was used to measure the porosity. Via x-ray diffraction the phase composition of the cured samples was determined.

Elongated curing slightly decreased the total porosity of the tested geopolymers. Higher curing temperature increased the compressive strength after 24 hour but did not affect strength for longer curing times. In general, the samples cured in moisture had higher mechanical strength than those cured in air. But low compression strength of samples cured under high temperature and long time showed that some water content in geopolymer was essential to retaining its microstructure.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Series
Ceramic Engineering and Science Proceedings
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-219258 (URN)10.1002/9781118807743.ch5 (DOI)
Conference
37th International Conference and Expo on Advanced Ceramics and Composites; 27 Jan - 1 Feb 2013; Daytona Beach, Fia., USA
Funder
Swedish Research Council
Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2015-04-17Bibliographically approved
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