Physical analysis of solid solution formulations

Student thesis: Doctoral Thesis

Abstract

Amorphous solid dispersion is one of the techniques used for enhancing dissolution rate of drugs with low aqueous solubility. The physical stability of the amorphous solid dispersion is the main challenge for their formulation development and commercialisation by pharmaceutical industry. The aims of the project were to prepare amorphous solid solution of a poorly aqueous soluble drug using different molecular weight mixtures of PEG and PEG mixed with other polymers such as PVP and poloxamers, the formulations were prepared using melt method, solvent evaporation and quench cooled from melt method. Also, to find a system with controlled instability to study the impact of various features on the stability of the formulation. A series of physicochemical characterisation techniques were used to evaluate the different formulations such as XRPD, VT XRPD, DSC, dissolution and microscopy.The cooling temperature of the formulation from melt has a great impact on forming amorphous CBZ in PEG mixture. PEG 300 did show the ability to reduce the crystallinity in the other PEG used and to reduce the enthalpy of CBZ recrystallisation which indicates that less crystals been formed. The higher the PEG concentration in the formulation, the more stable the CBZ amorphous form. The best performing formulations in terms of controlling the recrystallisation of the CBZ from melt were the PEG 4000 and 6000 mixed with PEG 300, but their dissolution profile was not as good as the formulations with one PEG. The substitution of just5% of PEG weight with PVP did show an increase in CBZ amorphous form stability.The quench cooling method did not show any decomposition of CBZ and that was proven by the HPLC method used.CBZ amorphous solid solution can be achieved by formulating the drug with PEGusing melt method and the addition of secondary polymer such as PVP to the formulation at low concentration can inhibit the CBZ recrystallisation from the glassy/ liquid state and increases CBZ physical stability.
Date of Award3 Oct 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorGavin Halbert (Supervisor) & Steven Ford (Supervisor)

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