In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres

Pu, Chenguang; Wang, Qiao; Zhang, Hongjuan; Gou, Jingxin; Guo, Yuting; Tan, Xinyi; Xie, Bin; Yin, Na; He, Huan; Wang, Yanjiao; Yin, Tian

doi:10.1007/s11095-017-2258-4

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…In cases of cyclosporine A and norquetiapine, their EE values were 57.5 ± 3.0% and 48.3 ± 3.0%, respectively [26,27]. There are also a couple of studies encapsulating progesterone into PLGA microspheres via methylene chloride-based solvent evaporation methods [28,29]. Its EE values ranged from 78.2 to 84.6%.…”

Section: Characterization Of Plga Microspheres Prepared Using Ethyl Fmentioning

confidence: 99%

Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry

Shim

Sah

2020

Pharmaceutics

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Thermogravimetry does not give specific information on residual organic solvents in polymeric matrices unless it is hyphenated with the so-called evolved gas analysis. The purpose of this study was to apply, for the first time, derivative thermogravimetry (DTG) to characterize a residual solvent and a drug in poly-d,l-lactide-co-glycolide (PLGA) microspheres. Ethyl formate, an ICH class 3 solvent, was used to encapsulate progesterone into microspheres. DTG provided a distinct peak, displaying the onset and end temperatures at which ethyl formate started to evolve from to where it completely escaped out of the microspheres. DTG also gave the area and height of the solvent peak, as well as the temperature of the highest mass change rate of the microspheres. These derivative parameters allowed for the measurement of the amount of residual ethyl formate in the microspheres. Interestingly, progesterone affected not only the residual solvent amount but also these derivative parameters. Another intriguing finding was that there was a linear relationship between progesterone content and the peak height of ethyl formate. The residual solvent data calculated by DTG were quite comparable to those measured by gas chromatography. In summary, DTG could be an efficient and practical quality control tool to evaluate residual solvents and drugs in various polymeric matrices.

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Section: Characterization Of Plga Microspheres Prepared Using Ethyl Fmentioning

confidence: 99%

Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry

Shim

Sah

2020

Pharmaceutics

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“…C max of the implant occurred at approximately 12th day, and the mean plasma concentration–time profile of the microsphere (F 1-5) showed two peaks, among which the first little peak at the 12th day and the second peak at the 42nd day were mainly caused by GOS dispersed in the PLGA depot in a multihydrogel core, respectively (Figure ). The two peak plasma concentration profiles enabled the microspheres prepared by F 1-5 and F 1-10 to achieve AUC 0– t that is 9.36-fold and 7.52-fold greater than that of the Zoladex implant . The increased relative bioavailability could be ascribed to the higher plasma concentration peak by Poloxamer hydrogel depot .…”

Section: Resultsmentioning

confidence: 96%

“…The obtained data were analyzed using a noncompartmental method with Drug and Statistics (DAS) software (version 2.0, Mathematical Pharmacology Professional Committee of China, Shanghai, China). The area under a curve (AUC) was calculated according to the trapezoidal rule, and the absorption fraction ( f ) was acquired by eq . …”

Section: Methodsmentioning

confidence: 99%

Goserelin Acetate Loaded Poloxamer Hydrogel in PLGA Microspheres: Core–Shell Di-Depot Intramuscular Sustained Release Delivery System

Pan

Zhang

et al. 2019

Mol. Pharmaceutics

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This study aimed to prepare and optimize goserelin acetate (GOS) loaded hydrogel poly(D,L-lactic acid-coglycolic acid) (PLGA) microsphere that is suitable for long-acting clinical treatment, investigate its structure, and regulate the initial release manner. Here, the PLGA microsphere containing Poloxamer hydrogel loaded with ∼15% (w/w) GOS was prepared by double-emulsion−solvent evaporation method and evaluated in terms of microscopic structure, physicochemical properties, and release manner in vitro and in vivo. Raman volume imaging and scanning electron microscopy studies revealed a core−shell Di-Depot structure of the microsphere, in which multi-GOS-loaded hydrogel depots were distributed in the core region. Under the interaction of hydrogel and PLGA depots, high encapsulation efficiency (94.16%) and low burst release (less than 2%) were achieved, along with the accompanying prolonged administration interval (49 days); an enhanced relative bioavailability 9.36-fold higher than that of Zoladex implant was also observed. Also, by addition of 1−5% acetic acid, the lag time was shortened to 6 days. The strategy for regulating the initial release provides new insights for manipulating the release behavior of the PLGA microspheres. The desirable property of the Poloxamer hydrogel PLGA microsphere indicated its promising application in controlled release drug delivery system.

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“…17 Cai et al 16 found that when drug loading is as high as 20%, the FITC-dextran distributed as much bigger drug strands, some of which crystallize. Pu et al 12 discovered that progesterone in PLGA microspheres was in an amorphous form. However, the diffraction peak of progesterone began to emerge after 12 hours and the peak intensity gradually increased during the continuous release process.…”

Section: Dovepressmentioning

confidence: 99%

“…[9][10][11] The properties and interactions of the drug, PLGA, and solvent, usually collectively dictate the impact of formulation composition on microstructure. 12,13 Besides the formulation, the crucial manufacturing processes, such as emulsification, solidification, and drying, can generate LAI microspheres with distinct release performance. 14,15 The significant impact of microstructure on LAI microsphere product release behavior has been emphasized in numerous studies.…”

Section: Introductionmentioning

confidence: 99%

Microstructure Formation and Characterization of Long-Acting Injectable Microspheres: The Gateway to Fully Controlled Drug Release Pattern

Wang,

Zhang

et al. 2024

IJN

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Long-acting injectable microspheres have been on the market for more than three decades, but if calculated on the brand name, only 12 products have been approved by the FDA due to numerous challenges in achieving a fully controllable drug release pattern. Recently, more and more researches on the critical factors that determine the release kinetics of microspheres shifted from evaluating the typical physicochemical properties to exploring the microstructure. The microstructure of microspheres mainly includes the spatial distribution and the dispersed state of drug, PLGA and pores, which has been considered as one of the most important characteristics of microspheres, especially when comparative characterization of the microstructure (Q3) has been recommended by the FDA for the bioequivalence assessment. This review extracted the main variables affecting the microstructure formation from microsphere formulation compositions and preparation processes and highlighted the latest advances in microstructure characterization techniques. The further understanding of the microsphere microstructure has significant reference value for the development of longacting injectable microspheres, particularly for the development of the generic microspheres.

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In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres

Cited by 9 publications

References 39 publications

Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry

Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry

Goserelin Acetate Loaded Poloxamer Hydrogel in PLGA Microspheres: Core–Shell Di-Depot Intramuscular Sustained Release Delivery System

Microstructure Formation and Characterization of Long-Acting Injectable Microspheres: The Gateway to Fully Controlled Drug Release Pattern

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