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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3165–3176 | Cite as

Development and Characterisation of Modified Release Hard Gelatin Capsules, Based on In Situ Lipid Matrix Formation

  • Gábor Vasvári
  • Bence Csontos
  • Tamás Sovány
  • Géza RegdonJr
  • Attila Bényei
  • Judit Váradi
  • Ildikó Bácskay
  • Zoltán Ujhelyi
  • Pálma Fehér
  • Dávid Sinka
  • Thi Le Phuong Nguyen
  • Miklós Vecsernyés
  • Ferenc Fenyvesi
Research Article
  • 81 Downloads

Abstract

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 WORDS

lipid matrix in situ matrix formation Gelucire 50/13 hard gel capsule dissolution kinetics 

Notes

Acknowledgements

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.

Funding

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.

Supplementary material

12249_2018_1146_MOESM1_ESM.docx (14 kb)
ESM 1 (DOCX 14 kb)
12249_2018_1146_MOESM2_ESM.docx (13 kb)
ESM 2 (DOCX 12 kb)
12249_2018_1146_MOESM3_ESM.jpg (112 kb)
Fig. S1 Diffractograms of the pure APIs, Gelucire 50/13 and the fresh DS1, ACP1 and MNZ1 matrices. A pure DS, B fresh DS1, C pure ACP, D fresh ACP1, E pure MNZ, F fresh MNZ1, G pure GC. The collected frames were integrated, the raw pXRD curves are ordered and their sizes were adjusted to match at the same degree of 2 Theta. (JPG 111 kb)
12249_2018_1146_MOESM4_ESM.jpg (229 kb)
Fig. S2 HPLC assay chromatograms of the 2 years old DS matrices. Chromatograms of the 10× methanolic dilutions of the 2 years old A DS1, B DS2, C DS3. Impurity can be seen on A and B at 5.6 min. (JPG 228 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Gábor Vasvári
    • 1
  • Bence Csontos
    • 1
  • Tamás Sovány
    • 2
  • Géza RegdonJr
    • 2
  • Attila Bényei
    • 3
  • Judit Váradi
    • 1
  • Ildikó Bácskay
    • 1
  • Zoltán Ujhelyi
    • 1
  • Pálma Fehér
    • 1
  • Dávid Sinka
    • 1
  • Thi Le Phuong Nguyen
    • 1
  • Miklós Vecsernyés
    • 1
  • Ferenc Fenyvesi
    • 1
  1. 1.Department of Pharmaceutical TechnologyUniversity of DebrecenDebrecenHungary
  2. 2.Institute of Pharmaceutical Technology and Regulatory AffairsUniversity of SzegedSzegedHungary
  3. 3.Department of Physical ChemistryUniversity of DebrecenDebrecenHungary

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