Tailoring of biopolymer films for use in soft gel capsules Gelatin and carrageenan mixtures
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The pure mammalian gelatin soft gel capsules on the market today dissolve after a short time in the acidic environment in the ventricle. Problems related to this are loss of functionality of the drug contained in the capsule and discomfort due to reflux when ingesting e.g. capsules containing fish oil. One of the aims of this study was to improve the composition of gelatin soft gel capsules, so the release of capsule content is delayed until it reaches the small intestine. This controlled release will give more efficient delivery of certain acid-sensitive drugs, and reduce discomfort for the consumer. It was also desirable to incorporate fish gelatin (FG) in the capsules, while retaining the gel strength. In order for the systems to be used in capsule production, the gel strength must be adequate for the gels to with stand the strain inflicted on them during the encapsulation process. Based on the promising results of previous work on kappa-carrageenan (κCG)/gelatin mixtures, the approach of this study was to apply iota-carrageenan (ιCG) in mixture with gelatin. The greater net negative charge of ιCG compared to κCG indicated that it would interact stronger with net positively charged gelatin, resulting in stronger films. The second main objective of this work was to gain better understanding of the interaction between ιCG and gelatin and the phase separation that occurs in these mixtures. ιCG/gelatin mixtures of different compositions were tested as films in diffusion/dissolution experiments that mimic the in-vivo conditions in the ventricle, and the rate of release of paracetamol through the films was measured. From small strain oscillatory measurements the gel strength (G’), melting temperature and gelling temperature for the gels was obtained. Differential scanning calorimetry (DSC) was performed on films under different conditions, giving denaturation temperature and enthalpy change related to denaturation on a molecular level and phase transition. The mean percent released paracetamol in the diffusion/dissolution experiments was decreased from 100% for the pure mammalian gelatin (MG) films, to 4.4% for the most acid-resistant MG/ιCG films. The gel strength of the gels with ιCG was lower than for the pure mammalian gelatin, due to lower content of mammalian gelatin. A strong correlation between gel strength and concentration of MG was observed. The FG/ιCG films had relatively low release of paracetamol, but the gel strength was too low for capsule production. Diffusion experiments and rheology measurements were performed on ιCG/MG and κCG/MG systems of constant composition except from varying type of cation present. This revealed that the properties of the ιCG/MG films were relatively independent of the salt concentration and cation type present. In comparison, the κCG/MG systems showed high dependence of the κCG specific cation K+. DSC measurements showed an increase in denaturation temperature for the films with ιCG. This indicates that the ιCG participates in stabilization of the helical junction zones in gelatin, so more energy is required for denaturation of the gel network. Visual observation of type A MG/ιCG and type B MG/ιCG mixtures, as well as of films of the same type in artificial gastric juice, showed increased turbidity when the pH was lower than the IEP of the respective gelatin. This indicates that an associative phase separation occurs due to electrostatic interaction between gelatin and ιCG.