← Back to Search
Lipid Extrudates As Novel Sustained Release Systems For Pharmaceutical Proteins.
S. Schulze, G. Winter
Published 2009 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
In order to develop improved lipid-based implants for proteins, the applicability of twin screw extrusion as a manufacturing strategy was investigated. Using lipid blends of low and high melting lipids, extrusion could be performed at moderate temperatures. In addition to the lipids, the implant systems contained 10% rh-interferon alpha-2a (IFN-alpha) co-lyophilised with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and 10% or 20% polyethylene glycol (PEG), respectively. Protein integrity was analysed by SDS-PAGE after extraction. FTIR-spectroscopy was used as a non-invasive method to assess the secondary protein structure of IFN-alpha within the lipid extrudates. Both methods indicate the preservation of the protein structure. Depending on the diameter of the prepared extrudates and on the PEG content of the system, protein release occurred in a sustained manner over 15, 40, or 60 days. Interestingly, extrudates with a smaller diameter revealed a continuous release profile, whereas extrudates with a diameter of 1.9 mm delivered IFN-alpha in a triphasic profile with a burst, lag and linear release phase lasting over 13 or 26 days. In conclusion, lipid implants for proteins can be prepared by twin screw extrusion in an elegant and controllable manner that allows the adjustment of release characteristics.
This paper references
Controlled-release of diclofenac sodium from wax matrix granule
Yasuhiko Miyagawa (1996)
Lipospheres as Delivery Systems for Peptides and Proteins
Achim G√∂pferich (2004)
The Development of a Sustained and Controlled Release Device for Pharmaceutical Proteins based on Lipid Implants
S. Mohl (2004)
Instability, stabilization, and formulation of liquid protein pharmaceuticals.
W. Wang (1999)
Solid lipid extrusion of sustained release dosage forms.
C. Reitz (2007)
Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.
Y. Yamagata (2000)
New Insight into the Role of Polyethylene Glycol Acting as Protein Release Modifier in Lipidic Implants
S. Herrmann (2007)
Sustained Delivery of Proteins for Novel Therapeutic Products
R. Bartus (1998)
Protein secondary structures in water from second-derivative amide I infrared spectra.
A. Dong (1990)
pH and Osmotic Pressure Inside Biodegradable Microspheres During Erosion1
Anette Brunner (2004)
Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide)
Gaozhong Zhu (2000)
Lysozyme distribution and conformation in a biodegradable polymer matrix as determined by FTIR techniques.
M. van de Weert (2000)
Protein stability in controlled-release systems
K. Fu (2000)
Peptide Acylation by Poly(α-Hydroxy Esters)
A. Lucke (2004)
ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly(ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins.
T. Kissel (2002)
Polymorphic Behavior of Sprayed Lipid Micropellets and Its Evaluation by Differential Scanning Calorimetry and Scanning Electron Microscopy
T. Eldem (2004)
Release of Human Serum Albumin from Poly(lactide-co-glycolide) Microspheres
M. Hora (2004)
Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion.
J. Liu (2001)
Lipid implants as drug delivery systems
F. Kreye (2008)
An Investigation into the Effects of Preparation Conditions and Storage on the Rate of Drug Release from Pharmaceutical Glyceride Bases
W. Sutananta (1995)
Comparison of protein loaded poly(?-caprolactone) microparticles prepared by the hot-melt technique
W. Yu (2001)
A novel mathematical model quantifying drug release from lipid implants.
F. Siepmann (2008)
Temperature- and pH-Induced Multiple Partially Unfolded States of Recombinant Human Interferon-α2a: Possible Implications in Protein Stability
V. Sharma (2004)
Melted glyceryl palmitostearate (GPS) pellets for protein delivery.
T. Pongjanyakul (2004)
In vitro investigation of lipid implants as a controlled release system for interleukin-18.
S. Koennings (2006)
Lipids: An alternative material for protein and peptide release
A. Maschke (2004)
Development and characterization of lipid microparticles as a drug carrier for somatostatin.
H. Reithmeier (2001)
Drug release from lipid-based implants: elucidation of the underlying mass transport mechanisms.
C. Guse (2006)
Effects of protein aggregates: An immunologic perspective
A. Rosenberg (2008)
Use of infrared spectroscopy to assess secondary structure of human growth hormone within biodegradable microspheres.
T. H. Yang (1999)
Lipidic implants for controlled release of bioactive insulin: effects on cartilage engineered in vitro.
B. Appel (2006)
Optimization of Spray-Dried and -Congealed Lipid Micropellets and Characterization of Their Surface Morphology by Scanning Electron Microscopy
T. Eldem (2004)
Effect of aging on the release of salbutamol sulfate from lipid matrices.
A. San Vicente (2000)
Towards controlled release of BDNF--manufacturing strategies for protein-loaded lipid implants and biocompatibility evaluation in the brain.
S. Koennings (2007)
Preparing and evaluating delivery systems for proteins.
L. Jorgensen (2006)
Continuous release of rh-interferon α-2a from triglyceride matrices
S. Mohl (2004)
Improving enzymes by using them in organic solvents
Alexander M. Klibanov (2001)
Stabilization and Controlled Release of Bovine Serum Albumin Encapsulated in Poly(D, L-lactide) and Poly(ethylene glycol) Microsphere Blends
W. Jiang (2004)
FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres.
K. Fu (1999)
Encyclopedia of Pharmaceutical Technology
J. Swarbrick (2006)
Visual Evidence of Acidic Environment Within Degrading Poly(lactic-co-glycolic acid) (PLGA) Microspheres
K. Fu (2004)
Continuous Release of rh-Interferon α-2a from Triglyceride Implants: Storage Stability of the Dosage Forms
S. Mohl (2006)
Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers
C. Pérez (2002)
Understanding and increasing protein stability.
C. O. Fágáin (1995)
Biodegradable polymers for protein and peptide drug delivery.
W. Gombotz (1995)
Mathematical modeling of bioerodible, polymeric drug delivery systems.
J. Siepmann (2001)
Fourier Transform Infrared Spectroscopy
O. Faix (1992)
This paper is referenced by
Lipid‐coated mannitol core microparticles for sustained release of protein
B. Wang (2018)
Hot Melt Extrusion for Sustained Protein Release: Matrix Erosion and In Vitro Release of PLGA-Based Implants
Anne Cossé (2016)
Parenteral controlled drug delivery by novel direct injectable polymer (DIPO) - in situ forming implant
A. G. Rodrigues (2018)
Biopharmaceutical characterisation of insulin and recombinant human growth hormone loaded lipid submicron particles produced by supercritical gas micro-atomisation.
S. Salmaso (2009)
Development of lipid based depot formulations using interferon-beta-1b as a model protein
Christian Neuhofer (2015)
Solid lipid excipients - matrix agents for sustained drug delivery.
Y. Rosiaux (2014)
The development of PVP-based solid dispersions using hot melt extrusion for the preparation of immediate release formulations
Siok Yee Chan (2013)
Extruded lipid implants for intravitreal use - protein stability, release kinetics and process design
Moritz Vollrath (2017)
Industrial ram extrusion as innovative tool for the development of biodegradable sustained release implants
Martina Sprengholz (2014)
Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants
R. Shamma (2012)
Drug release mechanisms of cast lipid implants.
F. Kreye (2011)
Pharmazeutisches Produktdesign: Gezielte Freisetzung von Wirkstoffen durch unterschiedliche Extrusionstechniken
P. Kleinebudde (2011)
Encapsulation via Hot-Melt Extrusion
H. Patil (2015)
Development of microparticles for sustained release of proteins based on lipid and silica materials
B. Wang (2017)
MALDI-TOF MS imaging of controlled release implants.
F. Kreye (2012)
Controlled release implants based on cast lipid blends.
F. Kreye (2011)
Enhancing bioavailability through thermal processing.
Justin M Keen (2013)
An Approach to Modeling Protein Release from Lipid Implants
R. Blagoeva (2011)
The Development of Sustained Release Formulation for Pharmaceutical Proteins based on Vesicular Phospholipid Gels
W. Tian (2010)
Comparison of residence time models for pharmaceutical twin-screw-extrusion processes
Jens Wesholowski (2019)
Release pathways of interferon α2a molecules from lipid twin screw extrudates revealed by single molecule fluorescence microscopy.
Gerhard Sax (2012)
Production of laminar extrudates containing particles of a model drug processed by supercritical fluids
Gonçalo E. Oliveira (2015)
Lipid-based intravesical drug delivery systems with controlled release of trospium chloride for the urinary bladder.
M. Haupt (2013)
Novel pH-sensitive lipid-polymer composite microspheres of 10-hydroxycamptothecin exhibiting colon-specific biodistribution and reduced systemic absorption.
L. Gan (2013)
The preparation of lipid-based drug delivery system using melt extrusion.
G. Chauhan (2020)
Coupling purification and in situ immobilization process of monoclonal antibodies to clenbuterol for immunosensor application.
H. Cao (2015)
Formation of mannitol core microparticles for sustained release with lipid coating in a mini fluid bed system
B. Wang (2017)
Effect of excipients on encapsulation and release of insulin from spray‐dried solid lipid microparticles
Chengyu Wu (2018)
Methodology of oral formulation selection in the pharmaceutical industry.
M. Kuentz (2016)
In-vivo biodegradation of extruded lipid implants in rabbits.
Gerhard Sax (2012)
Lipid–polymer composite microspheres for colon-specific drug delivery prepared using an ultrasonic spray freeze-drying technique
Yiping Gao (2011)
Vesicular phospholipid gel-based depot formulations for pharmaceutical proteins: development and in vitro evaluation.
W. Tian (2010)See more