Modification of the tri-phasic drug release pattern of leuprolide acetate-loaded poly(lactide-co-glycolide) microparticles

Luan, Xiaosong; Bodmeier, Roland

doi:10.1016/j.ejpb.2005.12.010

Cited by 40 publications

(19 citation statements)

References 24 publications

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“…Drug release from the prepared microspheres followed the triphasic pattern previously described by other authors (34), resulting in a near-to-zero-order release pattern. Optimization of the release properties of the prepared microspheres took place through the variation of formulation parameters, such as PLGA concentration, in addition to emulsifier type and concentration.…”

Section: In Vitro Drug Release Profilesmentioning

confidence: 75%

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

et al. 2010

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Abstract. This study aimed at preparation of a sustained-release steroidal treatment for chronic inflammatory conditions, such as rheumatoid arthritis. To achieve such a goal, biodegradable polylactide-co-glycolide prednisolone-loaded microspheres were prepared using o/w emulsion solvent evaporation method. Formulation parameters were adjusted so as to optimize the microsphere characteristics. The prepared microspheres exhibited smooth and intact surfaces, with average size range not exceeding 65 µm. The encapsulation efficiency percent of most microsphere formulations fell within the range of 25-68%. Drug release from these microspheres took place over 4 weeks, with nearto-zero-order patterns. Two successful formulations were chosen for the treatment of unilateral arthritis, induced in mice using Freund's complete adjuvant (FCA). Inflammatory signs of adjuvant arthritis included severe swelling of the FCA-injected limbs, in addition to many histopathological lesions. These included inflammatory cell infiltration, synovial hyperplasia, cartilage, and bone erosion. Parenteral administration of the selected formulae dramatically reduced the swelling of the FCA-injected limbs. In addition, histological examination revealed that the microsphere treatment protocol efficiently protected cartilages and bones of mice, injected with FCA initial and booster doses, from erosion. These results could not be achieved by a single prednisolone dose of 5 mg/kg.

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Section: In Vitro Drug Release Profilesmentioning

confidence: 75%

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

et al. 2010

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“…After formation of the depot, drug molecules are blocked by double diffusion barriers whereby the drug must diffuse through microspheres to the SAIB depot first and then diffuse from the SAIB depot into the media, leading to a steady and slow drug release profile. Meanwhile, due to the application of low molecular weight PLGA and the decreased particle size (<10 μm), the ultra-small microspheres will ensure continuous and complete drug release as reported in the literature (15)(16)(17)(18)(19). As a result, the microsphere/SAIB hybrid depot can not only reduce the burst release of SAIB but also significantly prolong the drug release period of microspheres prepared with low molecular weight PLGA, rendering the hybrid depot a useful and practical long-term drug delivery system.…”

Section: Introductionmentioning

confidence: 97%

“…It is therefore essential to improve the triphasic drug release behavior of PLGA microspheres to provide continuous release without a lag-release phase to maintain the therapeutic effect of the drug in PLGA microspheres. To date, many efforts have been made to eliminate the lagphase and thus obtain continuous drug release: (1) increasing the water penetration by co-encapsulation of a pore agent in microspheres such as Mg(OH) 2 (6), stearic acid (14), and medium chain triglyceride (15), (2) improving the hydrophilic nature of PLGA by using low molecular weight PLGA (15)(16)(17), (3) and controlling the drug release by diffusion by preparing small-sized microspheres (e.g., smaller than 20 μm for small molecules) (18,19). Although the above approaches all successfully eliminate the lag-release phase by increasing the drug diffusion rate during the initial stage, problems, such as burst release and a significantly shortened drug release period caused by those approaches, have occurred.…”

Section: Introductionmentioning

confidence: 99%

A Uniform Ultra-Small Microsphere/SAIB Hybrid Depot with Low Burst Release for Long-Term Continuous Drug Release

Xia

Tang

et al. 2015

Pharm Res

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“…The release profile of the drug may be influenced by many parameters such as physicochemical properties and drug loading, variations of polymer molecular weight, lactic-to-glycolic ratio, microencapsulation conditions, and in vitro test protocols (14,15). This particular system usually shows a triphasic release profile characterized by an initial burst of the drug near the surface or associated with pores after polymer wetting, usually defined as the amount released during the first 24 h (15), a lag phase until sufficient polymer erosion has taken place, and a secondary burst with approximately zero-order release kinetics (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Release Testing of PLGA Microspheres with Franz Diffusion Cells

Herrera¹,

Tesoriero²,

Hermida³

2012

Dissolution Technol.

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In the present study, two methods were used to evaluate the in vitro release of leuprolide acetate (LA) from poly(lactide-co-glycolide) (PLGA) microspheres: Franz diffusion cells, typically referred to as "vertical diffusion cells" (VDC), and rotating bottle apparatus (RBA), both modified with a dialysis membrane. This hydrosoluble peptide was chosen as a model drug to study different possibilities of in vitro testing and analyze the variables that affect drug release, respecting sink and physiological conditions. Microspheres were prepared with a conventional double emulsion-solvent evaporation method using PLGA (50:50) with a relatively low molecular weight. Comprehensive stability tests for LA were performed in the conditions used for in vitro release assays. In phosphate-buffered saline (PBS), LA showed no significant degradation, but in an acidic medium, it degraded dramatically. The release profile of the delivery system was governed mainly by diffusion as explained by the low molecular weight of the polymer and the high water solubility of the peptide. The in vitro release profiles were triphasic in vertical diffusion cells and biphasic in the rotating bottle apparatus. The release kinetics was enhanced in RBA with respect to VDC, probably because the constant movement of a suspension of loose microspheres in a large volume and the large membrane area facilitated drug migration. The smoother, triphasic profiles obtained with VDC can be explained by the partial confinement of microspheres, which is similar to the described in vivo behavior of an injectable delivery system.

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Modification of the tri-phasic drug release pattern of leuprolide acetate-loaded poly(lactide-co-glycolide) microparticles

Cited by 40 publications

References 24 publications

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

Prednisolone-Loaded PLGA Microspheres. In Vitro Characterization and In Vivo Application in Adjuvant-Induced Arthritis in Mice

A Uniform Ultra-Small Microsphere/SAIB Hybrid Depot with Low Burst Release for Long-Term Continuous Drug Release

In Vitro Release Testing of PLGA Microspheres with Franz Diffusion Cells

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