How is carbamazepine synthesized

Controlled release and selective adsorption of carbamazepine using mesoporous silicates

Controlled Release and Selective Adsorption of Carbamazepine with Mesoporous Silica Materials

Please always quote using this URN: urn: nbn: de: bvb: 29-opus4-130474

Carina Bütterich

  • The aim of this work was to develop a drug delivery system based on mesoporous silicates for the rapid or controlled release of poorly water-soluble drugs. The focus was on the anti-epileptic carbamazepine (CBZ for short), a model active ingredient of BCS class II, which, due to its low water solubility, leaves the human body unchanged by up to 30% and therefore without a therapeutic effect [53]. Therefore, within the scope of this work, various mesoporous silicates were first synthesized, characterized and checked for use as an active ingredient storage system for CBZ. Carrier materials of the M41S were used and the aim of this work was the development of a drug carrier system based on mesoporous silicates for the rapid or controlled release of poorly water-soluble drugs. The focus was on the anti-epileptic carbamazepine (CBZ for short), a model active ingredient of BCS class II, which, due to its low water solubility, leaves the human body unchanged by up to 30% and therefore without a therapeutic effect [53]. Therefore, within the scope of this work, various mesoporous silicates were first synthesized, characterized and checked for use as an active ingredient storage system for CBZ. Carrier materials of the M41S and SBA families as well as the mesocellular foam MCF were evaluated. Furthermore, these materials have been functionalized with organic groups on the pore walls or in the pore walls in the form of periodic mesoporous organosilicates (English: Periodic Mesoporous Organosilica, short: PMO). The influence of the loading time was carried out using the MCM-41 as an example. The results from the series of tests mentioned show that a loading time of 1 hour is sufficient. An extension of the contact time up to 2.5 h leads neither to an increase in the loading amount nor to a further decrease in the CBZ crystallinity. A comparison of the inorganic M41S materials loaded with CBZ showed that an NSA value <1 is associated with a CBZ crystallinity below 10%. An NSA value << 1 is associated with a higher CBZ crystallinity, which suggests that the pores are blocked by CBZ. This cannot be generalized for the functionalized materials. In addition, MCM-48 samples with different template contents were loaded with CBZ. The reduction in the template content led to an increase in the NSA value with decreasing CBZ crystallinity in the MCM-48 material loaded with CBZ. A closer examination of other MCM-48 materials with different amounts of template residue in the pores therefore seems to make sense. To determine the storage stability of the CBZ introduced into the mesoporous silicates, the solids were stored under exclusion of light at room temperature and at 8 ° C. After three months, the CBZ crystallinity in the MCM-48 CBZ materials, SBA-15 CBZ and SBA 16 ethane PMO CBZ had increased. In the samples MCM 48-as CBZ and MCF CBZ, the CBZ crystallinity remained unchanged over the same time. Further storage of MCM-41-CBZ led to further amorphization of the CBZ. The mesoporous materials loaded with CBZ were investigated in in vitro release experiments. For the release rate constant k, the following sequence resulted for the M41S materials loaded with CBZ: MCM-48-APTMS
  • The aim of this thesis was to develop an active ingredient carrier system based on mesoporous silica for the rapid or controlled release of poorly water-soluble drugs. The focus was on the antiepileptic drug carbamazepine (short: CBZ), a model drug of the BCS class II. Due to ist low water solubility this drug is excreted up to almost 30% unaltered in the faeces and thus remains without therapeutic effect [53 ] Therefore, as part of this thesis, various mesoporous silica materials were first synthesized, characterized and tested for use as an active ingredient storage system for CBZ. Carrier materials from the M41S and SBA family, as well as the mesocellular foam MCF, were evaluated. The aim of this thesis was to develop an active ingredient carrier system based on mesoporous silica for the rapid or controlled release of poorly water-soluble drugs. The focus was on the antiepileptic drug carbamazepine (short: CBZ), a model drug of the BCS class II. Due to ist low water solubility this drug is excreted up to almost 30% unaltered in the faeces and thus remains without therapeutic effect [53 ] Therefore, as part of this thesis, various mesoporous silica materials were first synthesized, characterized and tested for use as an active ingredient storage system for CBZ. Carrier materials from the M41S and SBA family, as well as the mesocellular foam MCF, were evaluated. Furthermore, these mesoporous silica materials were functionalized with organic groups on the pore walls or in the pore walls in the form of periodic mesoporous organosilicas (short: PMOs). The influence of the loading time was carried out on MCM-41. The results show that a loading time of 1 h is sufficient. Extending the contact time up to 2.5 h does not lead to an increase in the amount of loading or to a further reduction of the CBZ crystallinity. A comparison of the inorganic M41S materials loaded with CBZ showed a correlation between an NSA value <1 and a CBZ crystallinity below 10%. An NSA value << 1 is associated with higher CBZ crystallinity, which suggests CBZ blocking the pores of the mesoporous silica. This cannot be generalized for the functionalized materials. In addition, MCM-48 samples with varying template content were loaded with CBZ. The reduction in template content led to an increase in the NSA value with decreasing CBZ crystallinity in the MCM-48 material loaded with CBZ. Researching further MCM-48 materials with different amounts of template residue in the pores would therefore be wise. In order to determine the storage stability of the CBZ encapsulated into the mesoporous silicas, the solids were stored under light exclusion at room temperature and refrigerated at 8 ° C. After three months, the CBZ crystallinity had increased in the materials MCM-48 CBZ, SBA-15 CBZ and SBA 16 Ethane PMO CBZ. In the samples MCM-48-as CBZ and MCF CBZ, the CBZ crystallinity remained unchanged over the same period. Further storage of MCM-41-CBZ led to a further amorphization of the CBZ. The mesoporous silica materials loaded with CBZ were evaluated in in-vitro dissolution tests. For the release rate constant k, the order of M41S materials loaded with CBZ was the following MCM-48-APTMS