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Lipid Based Formulations in Hard Gelatin and HPMC Capsules: a Physical Compatibility Study

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Abstract

Purpose

To investigate the compatibility between hard gelatin and HPMC capsules with a range of different isotropic lipid based formulations containing multiple excipients.

Methods

The miscibility was investigated for 350 systems applying five different oils (Labrafac ™ lipophile WL1349, Maisine® CC, Captex 300 EP/NF, olive oil, and Capmul MCM EP/NF), five different surfactans (Labrasol ® ALF, Labrafil M 2125 CS, Kolliphor ® ELP, Kolliphor ® HS 15, Tween 80) and three different cosolvents (propylene glycol, polyethylene glycol 400, and Transcutol ® HP). For the isotropic systems capsule compatibility was investigated in both gelatin and HPMC capsules at 25°C at 40% and 60% relative humidity by examining physical damages to the capsules and weight changes after storage.

Results

The miscibility of lipid based vehicles was best when the formulation contained monoglycerides and surfactants with a hydrophilic–lipophilic balance value <12. Gelatin capsules in general resulted in a better compatibility when compared to HPMC capsules for the evaluated formulations. Addition of water to the formulation improved the capsule compatibility for both capsule types. The expected capsule mass change could partly be predicted in binary systems using the provided data of the single excipients weighted for its formulation proportion.

Conclusions

The capsule compatibility was driven by the components incorporated into the formulations, where more was compatible with gelatin than HPMC capsules. Prediction of the mass change from individual excipient contributions can provide a good first estimate if a vehicle is compatible with a capsule, however, this needs to be proved experimentally.

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Author notes

    Authors and Affiliations

    1. Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium

      Niklas J. Koehl, Sanket Shah, Ingrid Djouka Tenekam, Sien Vingerhoets & René Holm

    2. Quantitative Sciences, Janssen Research and Development, Johnson and Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium

      Tatsiana Khamiakova & Hans Coppenolle

    3. Open Analytics NV, Jupiterstraat 20, 2600, Antwerp, Belgium

      Nicolas Sauwen

    4. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark

      René Holm

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    1. Niklas J. Koehl
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    Correspondence to René Holm.

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    Niklas J. Koehl and Sanket Shah contributed equally to this work.

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    Koehl, N.J., Shah, S., Tenekam, I.D. et al. Lipid Based Formulations in Hard Gelatin and HPMC Capsules: a Physical Compatibility Study. Pharm Res 38, 1439–1454 (2021). https://doi.org/10.1007/s11095-021-03088-8

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