Development and Characterisation of Modified Release Hard Gelatin Capsules, Based on In Situ Lipid Matrix Formation
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A new technology was developed to form extended release hard gelatin capsules, based on the lipid matrix formation of Gelucire 50/13 and cetostearyl alcohol. Matrices were formed in situ by filling pulverised lipids, ethylcellulose and active ingredients such as diclofenac sodium, acetaminophen and metronidazol into capsules and heating at 63°C for 11 min. Effects of heating were investigated also on the brittleness of capsule shells. Inhibition of the evaporation of water reduced capsule damage. Dissolution tests and texture analysis were performed to discover the release and mechanical profiles of the matrices. Tests were repeated after 1 month storage and results were compared. Gelucire 50/13 alone prolonged drug release but cetostearyl alcohol slowed drug liberation even further. Drug release from all compositions was found to follow first-order kinetic. Significant softening of the matrices was detected during storage in composition containing only Gelucire 50/13, ethylcellulose and diclofenac sodium. Thermal analysis and IR tests were also performed to discover physicochemical interactions between active pharmaceutical ingredients and excipients. Thermal analysis confirmed a notable interaction between diclofenac sodium and Gelucire 50/13 which could be the cause of the observed softening. In conclusion, modified release hard gelatin capsules were developed by a simple and fast monolithic lipid matrix formation method.
KEY WORDSlipid matrix in situ matrix formation Gelucire 50/13 hard gel capsule dissolution kinetics
Ágnes Hajdu from Azelis Hungary is acknowledged for providing the continuous contact with Gattefossé and suppling Gelucire samples. Last but not least, Erik Schwendtner from Colorcon Hungary is gratefully thanked for providing free sample and information about the applications of different Ethocel grades.
This paper was supported by the János Bolyai Research Scholarsip of the Hungarian Academy of sciences (BO/00290/16/5). The publication is supported by the EFOP-3.6.1-16-2016-00022 projects. The project is co-financed by the European Union and the European Social Fund. This research was also supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of GINOP-2.3.2-15-2016-00043.
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