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Title: Optimization of drug carrier interactions in spray dried solid dispersions
Author: Al-Obaidi, Hisham Kadhim Hashim
ISNI:       0000 0004 2668 2150
Awarding Body: University College London
Current Institution: University College London (University of London)
Date of Award: 2008
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The poor aqueous solubility of hydrophobic drugs has always been a challenge for formulation scientists. One approach to increase the dissolution rate of hydrophobic drugs is the use of solid dispersion that involves the molecular mixing of the drug with hydrophilic polymers. In addition to increased wettability of the drug, the drug can be prepared in the amorphous form which is associated with higher dissolution rate than the crystalline form. However, this form is physically unstable and materials tend to form the more stable crystalline form. In this thesis, the focus was on increasing the physical stability of amorphous hydrophobic drugs. The hypothesis was based on hydrogen bonding between the drug and the polymer. The model drugs contained proton acceptor groups in order to test the hypothesis. A third polymer was used as a linker to form hydrogen bonds with the drug and the polymer. Griseofulvin, progesterone and pheninedione were used as model drugs while poly [N-(2-hydroxypropyl)methacrylate] (PHPMA) was used as the linker molecule since it contains proton acceptor and donor groups while polyvinyl pyrrolidone (PVP) was used as the third polymer. The drug, PHPMA and PVP were spray dried to prepare amorphous solid dispersions. The results showed that the griseofulvin is more stable than the other two model drugs as confirmed by XRPD. Using the Flory-Huggins model, it was possible to calculate the entropy, enthalpy and free energy of mixing the drug with PHPMA. The results coincided with the stability data which suggest that PHPMA increases the miscibility of the drug with PVP. The above solid dispersions were compared against other solid dispersions containing cellulose based polymers since these polymers could form hydrogen bonding with the drug. The dissolution studies were carried on to investigate the mechanisms of drug release from the solid dispersion. The factors which could influence the strength of hydrogen bonding were investigated. These included the concentration of the drug and polymers, the solvents used, incorporation of surfactants, order of adding the drug and polymers and the spray drying parameters. The results showed that significant differences could be obtained when one of these factors is varied.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available