The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

Jingying Liu; Philip C Christophersen; Mingshi Yang; Hanne M Nielsen; Huiling Mu

doi:10.1080/03639045.2017.1361967

The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

Jingying Liu, Philip C Christophersen, Mingshi Yang, Hanne M Nielsen, Huiling Mu

Abstract

OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.

METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.

RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.

CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

Original language	English
Journal	Drug Development and Industrial Pharmacy
Volume	43
Issue number	12
Pages (from-to)	2032-2042
Number of pages	11
ISSN	0363-9045
DOIs	https://doi.org/10.1080/03639045.2017.1361967
Publication status	Published - 2 Dec 2017

Keywords

Administration, Oral
Calorimetry, Differential Scanning
Chemistry, Pharmaceutical
Drug Delivery Systems
Excipients
Lipids
Microscopy, Electron, Scanning
Muramidase
Proteins
Triglycerides
X-Ray Diffraction
Journal Article

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10.1080/03639045.2017.1361967

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The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. / Liu, Jingying; Christophersen, Philip C; Yang, Mingshi et al.

In: Drug Development and Industrial Pharmacy, Vol. 43, No. 12, 02.12.2017, p. 2032-2042.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles",

abstract = "OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.",

keywords = "Administration, Oral, Calorimetry, Differential Scanning, Chemistry, Pharmaceutical, Drug Delivery Systems, Excipients, Lipids, Microscopy, Electron, Scanning, Muramidase, Proteins, Triglycerides, X-Ray Diffraction, Journal Article",

author = "Jingying Liu and Christophersen, {Philip C} and Mingshi Yang and Nielsen, {Hanne M} and Huiling Mu",

year = "2017",

month = dec,

day = "2",

doi = "10.1080/03639045.2017.1361967",

language = "English",

volume = "43",

pages = "2032--2042",

journal = "Drug Development and Industrial Pharmacy",

issn = "0363-9045",

publisher = "Taylor & Francis",

number = "12",

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TY - JOUR

T1 - The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

AU - Liu, Jingying

AU - Christophersen, Philip C

AU - Yang, Mingshi

AU - Nielsen, Hanne M

AU - Mu, Huiling

PY - 2017/12/2

Y1 - 2017/12/2

N2 - OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

AB - OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.METHODS: Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.RESULTS: Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.CONCLUSIONS: Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.

KW - Administration, Oral

KW - Calorimetry, Differential Scanning

KW - Chemistry, Pharmaceutical

KW - Drug Delivery Systems

KW - Excipients

KW - Lipids

KW - Microscopy, Electron, Scanning

KW - Muramidase

KW - Proteins

KW - Triglycerides

KW - X-Ray Diffraction

KW - Journal Article

U2 - 10.1080/03639045.2017.1361967

DO - 10.1080/03639045.2017.1361967

M3 - Journal article

C2 - 28756687

SN - 0363-9045

VL - 43

SP - 2032

EP - 2042

JO - Drug Development and Industrial Pharmacy

JF - Drug Development and Industrial Pharmacy

IS - 12

ER -

The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

Abstract

Keywords

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