Development of Level A in vitro-in vivo correlations for peptide loaded PLGA microspheres

Andhariya, Janki V.; Jog, Rajan; Shen, Jie; Choi, Stephanie; Wu, Yan; Zou, Yuan; Burgess, Diane J.

doi:10.1016/j.jconrel.2019.07.013

Cited by 67 publications

(28 citation statements)

References 28 publications

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“…A similar effect was observed in a study by Andhariya et al in vivo, when upon i.m. administration of leuprolide acetate loaded PLGA microspheres, considerably lower drug plasma concentrations were detected in the initial stage compared with a high burst release in vitro (49). The authors attributed this effect to the additional step of diffusion and absorption of the peptide from the muscle tissue; yet the overall release was, nonetheless, faster in vivo.…”

Section: Discussionmentioning

confidence: 99%

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres

2021

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Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro, these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.

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Section: Discussionmentioning

confidence: 99%

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres

2021

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“…Also, the in vitro results alone are not necessarily a good representation of the dissolution/ absorption of the drug in vivo due to the complicated biological systems (51,52). Developing an in vitro-in vivo correlation (IVIVC) will help to predict how a drug will work in the body (53,54).…”

Section: Discussionmentioning

confidence: 99%

Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose

et al. 2021

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Purpose Opioids have been the main factor for drug overdose deaths in the United States. Current naloxone delivery systems are effective in mitigating the opioid effects only for hours. Naloxone-loaded poly(lactide-co-glycolide) (PLGA) microparticles were prepared as quick-and long-acting naloxone delivery systems to extend the naloxone effect as an opioid antidote. Methods The naloxone-PLGA microparticles were made using an emulsification solvent extraction approach with different formulation and processing parameters. Two PLGA polymers with the lactide:glycolide (L:G) ratios of 50:50 and 75:25 were used, and the drug loading was varied from 21% to 51%. Two different microparticles of different sizes with the average diameters of 23 μm and 50 μm were produced using two homogenization-sieving conditions. All the microparticles were critically characterized, and three of them were evaluated with β-arrestin recruitment assays. Results The naloxone encapsulation efficiency (EE) was in the range of 70-85%. The EE was enhanced when the theoretical naloxone loading was increased from 30% to 60%, the L:G ratio was changed from 50:50 to 75:25, and the average size of the particles was reduced from 50 μm to 23 μm. The in vitro naloxone release duration ranged from 4 to 35 days. Reducing the average size of the microparticles from 50 μm to 23 μm helped eliminate the lag phase and obtain the steadystate drug release profile. The cellular pharmacodynamics of three selected formulations were evaluated by applying DAMGO, a synthetic opioid peptide agonist to a μ-opioid receptor, to recruit β-arrestin 2. Conclusions Naloxone released from the three selected formulations could inhibit DAMGO-induced β-arrestin 2 recruitment. This indicates that the proposed naloxone delivery system is adequate for opioid reversal during the naloxone release duration. KEY WORDS β-arrestin 2 inhibition . DAMGO . drug loading . encapsulation efficiency . naloxone . opioid overdose . PLGA microparticles . zero-order release

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“…This was further verified by SEM, which showed the different effects of EA and DCM on the morphology and internal structure of the microspheres. Generally, microspheres prepared by DCM have a rounder surface than those prepared by EA [20,21]. The porosity of Vivitrol ® and the GNM was 51.59 ± 2.56 and 59.11 ± 2.73%, respectively.…”

Section: Residual Eamentioning

confidence: 96%

Key Factor Study for Generic Long-Acting PLGA Microspheres Based on a Reverse Engineering of Vivitrol®

Hua¹,

Wang²,

Wang³

et al. 2021

Molecules

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The FDA (U.S. Food and Drug Administration) has approved only a negligible number of poly(lactide-co-glycolide) (PLGA)-based microsphere formulations, indicating the difficulty in developing a PLGA microsphere. A thorough understanding of microsphere formulations is essential to meet the challenge of developing innovative or generic microspheres. In this study, the key factors, especially the key process factors of the marketed PLGA microspheres, were revealed for the first time via a reverse engineering study on Vivitrol® and verified by the development of a generic naltrexone-loaded microsphere (GNM). Qualitative and quantitative similarity with Vivitrol®, in terms of inactive ingredients, was accomplished by the determination of PLGA. Physicochemical characterization of Vivitrol® helped to identify the critical process parameters in each manufacturing step. After being prepared according to the process parameters revealed by reverse engineering, the GNM demonstrated similarity to Vivitrol® in terms of quality attributes and in vitro release (f2 = 65.3). The research on the development of bioequivalent microspheres based on the similar technology of Vivitrol® will benefit the development of other generic or innovative microspheres.

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Development of Level A in vitro-in vivo correlations for peptide loaded PLGA microspheres

Cited by 67 publications

References 28 publications

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres

Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose

Key Factor Study for Generic Long-Acting PLGA Microspheres Based on a Reverse Engineering of Vivitrol®

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