Protein release from poly(lactide-co-glycolide) implants prepared by hot-melt extrusion: Thioester formation as a reason for incomplete release

Ghalanbor, Zahra; Körber, Martin; Bodmeier, Roland

doi:10.1016/j.ijpharm.2012.09.015

Cited by 44 publications

(39 citation statements)

References 20 publications

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“…In another study by the same group, they used bovine serum albumin (BSA) as a model drug to prepare BSA-PLGA implants using HME with a special focus on identifying the reasons for incomplete release (93). The implant was prepared using a syringe-die extrusion device.…”

Section: Implantsmentioning

confidence: 99%

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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Abstract. Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

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Section: Implantsmentioning

confidence: 99%

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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“…Aliphatic polyesters have been comprehensively reviewed [31,[33][34][35][36]. They can be developed from a variety of monomers using various synthetic routes, resulting in polymers of variable molecular weight and degradation kinetics such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(e-caprolactone) (PCL) or copolymers such as poly(lactide-co-glycolide) with different lactide:glycolide ratios [37][38][39] and copolymers of ecaprolactone and L,D-lactide or glycolide [40]. Aliphatic polyesters degrade mainly by bulk erosion, usually having nonlinear and discontinuous erosion kinetics [41], which makes it difficult to predict the drug release kinetics.…”

Section: Aliphatic Polyestersmentioning

confidence: 99%

“…By contrast, in another study by the same group, BSA encapsulated into PLGA implants by HME resulted in an incomplete release. Ghalanbor et al revealed that the reason for an incomplete release of BSA from implants was acylation of BSA by thioester formation [38]. A complete and faster release was achieved by increasing the porosity and loading of implants [38] or by the incorporation of plasticizers, which increased the freevolume of the polymer [72].…”

Section: Biodegradable Water-insoluble Polymersmentioning

confidence: 99%

“…Ghalanbor et al revealed that the reason for an incomplete release of BSA from implants was acylation of BSA by thioester formation [38]. A complete and faster release was achieved by increasing the porosity and loading of implants [38] or by the incorporation of plasticizers, which increased the freevolume of the polymer [72]. Stanković et al prepared implants by low temperature extrusion (558C), using a novel multiblock copolymer composed of PCL in the semi-crystalline block and PCL-PEG in the amorphous block (PCL-PEG/PCL).…”

Section: Biodegradable Water-insoluble Polymersmentioning

confidence: 99%

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Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

Stanković

Frijlink

Hinrichs

2015

Drug Discovery Today

107

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“…A major issue in the meltprocessing of biomacromolecules is the high temperatures necessary, typically within the range of 95 -200 C. These elevated temperatures can cause the biomacromolecules to aggregate and denature within the polymer melt and remain once cooled [2]. The aggregation can result in loss of the desired activity of the biomacromolecule once released, irregular release profiles, or segregation of the biomacromolecule within the matrix resulting in diminished overall composite mechanical properties.…”

mentioning

confidence: 99%

Analysis of Polymer-Biomacromolecule Composites in the Solid-State via Energy Dispersive Spectroscopy-Scanning Electron Microscopy

2017

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The analysis and mapping of the dispersion of biomacromolecules within solid-state polymeric materials prepared via melt-processing is important in understanding the aggregation behavior in response to different loading levels, additives, and biochemical properties of the biomacromolecules. The presence of biomacromolecules can impart new properties to the material, such as flame retardant properties, or therapeutic value through controlled release from the polymer matrix [1]. A major issue in the meltprocessing of biomacromolecules is the high temperatures necessary, typically within the range of 95 -200 C. These elevated temperatures can cause the biomacromolecules to aggregate and denature within the polymer melt and remain once cooled [2]. The aggregation can result in loss of the desired activity of the biomacromolecule once released, irregular release profiles, or segregation of the biomacromolecule within the matrix resulting in diminished overall composite mechanical properties.The particular biomacromolecules of interest for this study were deoxyribonucleic acid (DNA) and viruslike particles (VLPs) as additives. The DNA was melt-processed with low-density polyethylene (LDPE) to impart flame retardant properties and the VLPs were melt-processed with poly(lactic-co-glycolic acid) (PLGA) to create sustained release depot systems. Backscattered electron (BSE) imaging is not sufficient to distinguish the difference between polymer and biomacromolecule because both largely consist of carbon. Another limitation with BSE imaging is the mass contrast can be easily overwhelmed by topographic contrast. However, energy dispersive spectroscopy (EDS) in scanning electron microscopy (SEM) is a valuable tool for biomacromolecule detection. Using the distinct chemical signatures in biomacromolecules, such as nitrogen, sulfur, and phosphorus, biomacromolecule dispersion can be successfully detected [3]. Here we report the impact of sample preparation and collection conditions on EDS mapping for DNA and VLP elemental signatures.The effects of freeze-fracturing versus cryo-microtoming surface preparation on the apparent dispersion of DNA within the LDPE matrix was investigated at two different concentrations of DNA. Cryomicrotoming the surface enhanced the ability to correctly discern and co-localize the elemental signals from DNA within the LDPE matrix. The interplay between image quality and signal intensity for VLPs embedded within PLGA was also explored in this study. PLGA deteriorates rapidly under high voltages, however higher voltages are necessary to yield signal from the relatively low-loading levels of VLPs and the elemental percent of VLP that is a distinguishable elemental signal. The effective voltage necessary for mapping the signal, while allowing for the preservation of the SEM image and visualization of the distribution of VLPs within the PLGA matrix was determined. These studies demonstrate the power of EDS-SEM for mapping biomacromolecules in solid-state polymer matrices and highlights considerations in...

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Protein release from poly(lactide-co-glycolide) implants prepared by hot-melt extrusion: Thioester formation as a reason for incomplete release

Cited by 44 publications

References 20 publications

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

Analysis of Polymer-Biomacromolecule Composites in the Solid-State via Energy Dispersive Spectroscopy-Scanning Electron Microscopy

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