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Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs II – The Digestion of Trilaurin Protects Desmopressin from Proteolytic Degradation

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ABSTRACT

Purpose

To investigate the in vitro release and degradation of desmopressin from saturated triglyceride microparticles under both lipolytic and proteolytic conditions.

Methods

The release of desmopressin from different solid lipid microparticles in the absence and presence of a microbial lipase and protease was determined. Trilaurin (TG12), trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18) were used as lipid excipients to produce solid lipid microparticles.

Results

In the presence of lipase, the rate of drug release from different lipid particles was in the order of TG14 > TG16 > TG18, which is the same rank order as the lipid degradation rate. A reverse rank order was found for the protection of desmopressin from enzymatic degradation due to spatial separation of desmopressin from the protease. TG12 accelerated the release of desmopressin from all lipid particles when added as either drug-free microparticles to the lipolysis medium or incorporated in TG16 particles. Additionally, TG12 particles protected desmopressin from degradation when present in the lipolysis medium with the other lipid microparticles.

Conclusions

TG12 is a very interesting lipid for oral lipid formulations containing peptides and proteins as it alters release and degradation of the incorporated desmopressin. The present study demonstrates the possibility of bio-relevant in vitro evaluation of lipid-based solid particles.

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ACKNOWLEDGMENTS AND DISCLOSURES

Dorthe Ørbæk (University of Copenhagen, Denmark) is acknowledged for her technical assistance with SEM imaging.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Philip Carsten Christophersen, Long Zhang, Anette Müllertz, Hanne Mørck Nielsen, Mingshi Yang & Huiling Mu

  2. Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Anette Müllertz

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  1. Philip Carsten Christophersen
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  2. Long Zhang
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  3. Anette Müllertz
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  4. Hanne Mørck Nielsen
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  5. Mingshi Yang
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  6. Huiling Mu
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Correspondence to Huiling Mu.

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Christophersen, P.C., Zhang, L., Müllertz, A. et al. Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs II – The Digestion of Trilaurin Protects Desmopressin from Proteolytic Degradation. Pharm Res 31, 2420–2428 (2014). https://doi.org/10.1007/s11095-014-1337-z

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  • DOI: https://doi.org/10.1007/s11095-014-1337-z

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