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Formulation and physico-chemical characterisation of novel films and wafers for mucosal drug delivery

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  • Qd Chemistry
  • Chemistry
  • Earth Science
  • Pharmacology


Development of novel drug delivery systems has become a major research endeavour in the pharmaceutical industry. Drug administration via the traditional oral route (GIT) presents certain challenges including enzymatic and acid break down of labile drugs and first pass metabolism in the liver. The research reported in this thesis involved the development of solvent cast films and freeze-dried wafers for the potential delivery of drugs via the buccal mucosa. The formulations were prepared from two polymers (κ-carrageenan (CAR) 911 and poloxamer 407 (P407)), two types of plasticizers (glycerol (GLY)) and various grades of polyethylene glycol (PEG) using paracetamol (PM), ibuprofen (IBU) and indomethacin (IND) as model drugs. The investigations involved extensive evaluation/characterisation of the initial formulation components and their optimum combinations to obtain the desired formulation by employing various physico-chemical characterisation techniques. Texture analysis was used to investigate the tensile properties (percent elongation and elastic modulus) of the films, the resistance of the films upon stretching as well as the behaviour of the films during handling. In the case of the wafers, texture analysis was used to determine the compressibility as well as in vitro mucoadhesive characteristics. The stability of both the initial components and within the formulated films or wafers was studied using thermal analysis (HSM, TGA and DSC). Thermogravimetric analysis (TGA) was used to estimate the residual water content of both formulations. XRPD was used to assess the different forms (amorphous or crystalline) of the various components, including the model drugs. Scanning electron microscopy provided topographic information with regard to surface architecture of the films and wafers. The drug loaded films and wafers were further characterised for chemical stability of the drugs, after storage at room temperature for twelve months and drug dissolution profiles using simulated saliva as dissolution medium. The results of the preliminary development and optimization experiments showed that gels prepared with 2.5% (w/w) CAR 911, in combination with 4% (w/w) P407 and 5.5% (w/w) PEG 600 produced a flexible film with ‘ideal’ characteristics and was selected for drug incorporation. However, the concentration of PEG was increased to 6% (w/w) in the presence of 1.6% w/w PM, and 6.5% (w/w) PEG with 0.6% (w/w) IND and 0.8% w/w IBU (concentrations relative total drug weight of film matrix). The initial results from the wafers demonstrated that a flexible wafer, obtained by freeze-drying (incorporating an annealing step), could be produced from a gel containing 2% (w/w) CAR 911 in combination with 4% (w/w) P407 and 4.4% (w/w) PEG 600. Addition of 0.8% (w/w) IBU also increased the flexibility of the wafer approximately two fold, whilst the flexibility of 1.8% (w/w) PM and 0.6% (w/w) IND loaded wafers was slightly reduced. TGA experiments indicated a water content of approximately 5% and 1% for films and wafers, respectively. SEM experiments revealed an even surface without any macroscopic pores for the film whilst the microstructure of the wafer was observed as being porous. The data from DSC experiments demonstrated interactions between P407 and PEG 600 during film formation. Furthermore, the conversion of the originally added model crystalline drugs into the amorphous form within the film and wafers was ascertained by DSC and confirmed by XRPD.

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