PBPK modeling coupled with biorelevant dissolution to forecast the oral performance of amorphous solid dispersion formulations

Kambayashi, Atsushi; Kiyota, Tsuyoshi; Fujiwara, Maya; Dressman, Jennifer B.

doi:10.1016/j.ejps.2019.05.013

Cited by 35 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PBPK models have great extrapolation and prediction power and thus have attracted increasing attention in the formulation design and clinical trials of new drugs. Reportedly, PBPK models have been applied to predict the bio-performance of amorphous drug SDs [ 24 , 25 ]. Meanwhile, PBPK models were used to design the dose regimen by combining the PK profile with the pharmacodynamics (PD) value [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

Zhou

Huo

et al. 2021

Pharmaceutics

View full text Add to dashboard Cite

Zoonotic intestinal pathogens threaten human health and cause huge economic losses in farming. Enrofloxacin (ENR) shows high antibacterial activity against common intestinal bacteria. However, its poor palatability and low aqueous solubility limit the clinical application of ENR. To obtain an ENR oral preparation with good palatability and high solubility, a granule containing an amorphous ENR solid dispersion (ENR-SD) was prepared. Meanwhile, a PBPK model of ENR in pigs was built based on the physiological parameters of pigs and the chemical-specific parameters of ENR to simulate the pharmacokinetics (PK) of ENR-SD granules in the intestinal contents. According to the results of parameter sensitivity analysis (PSA) and the predicted PK parameters at different doses of the model, formulation strategies and potential dose regimens against common intestinal infections were provided. The DSC and XRD results showed that no specific interactions existed between the excipients and ENR during the compatibility tests, and ENR presented as an amorphous form in ENR-SD. Based on the similar PK performance of ENR-SD granules and the commercial ENR soluble powder suggesting continued enhancement of the solubility of ENR, a higher drug concentration in intestinal contents could not be obtained. Therefore, a 1:5 ratio of ENR and stearic acid possessing a saturated aqueous solubility of 1190 ± 7.71 µg/mL was selected. The predictive AUC24h/MIC90 ratios against Campylobacter jejuni, Salmonella, and Escherichia coli were 133, 266 and 8520 (>100), respectively, suggesting that satisfactory efficacy against common intestinal infections would be achieved at a dose of 10 mg/kg b.w. once daily. The PSA results indicated that the intestinal absorption rate constant (Ka) was negatively correlated with the Cmax of ENR in the intestine, suggesting that we could obtain higher intestinal Cmax using P-gp inducers to reduce Ka, thus obtaining a higher Cmax. Our studies suggested that the PBPK model is an excellent tool for formulation and dose design.

show abstract

Section: Introductionmentioning

confidence: 99%

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

Zhou

Huo

et al. 2021

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Many drug candidates have low aqueous solubility, which can make their oral absorption inadequate. According to the literature, approximately 40% of marketed drugs are poorly soluble in water, as are, according to the Biopharmaceutical Classification System, about 40–90% of new drug candidates [ 1 , 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

et al. 2020

View full text Add to dashboard Cite

This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of their constituents. This bibliographic survey shows that the development of solid dispersions provides benefits in the physicochemical properties of bioactive compounds, which lead to an increase in their biological potential. However, despite the reports found on solid dispersions, there is still a need for biological assay-based studies, mainly in vivo, to assist in the investigation and to devise new applications. Therefore, studies based on such an approach are of great importance to enhance and extend the use of solid dispersions in the most diverse therapeutic applications.

show abstract

“…25) Furthermore, methods for the investigation of hydrogel formulations and amorphous solid dispersions-in which in vitro biorelevant dissolution testing is coupled with in silico modeling and simulation to predict oral absorption-may be relevant to the current gummi with SD formulations. 26,27) The findings of the current study suggest that PVA 66, PVA 66/88, and PVA 80 are suitable in terms of dissolution, stabil- Each geometric mean ratio between two phases is given with the corresponding 90% confidence interval.…”

Section: Discussionmentioning

confidence: 76%

Gummi Formulations Comprising Amenamevir Solid Dispersions with Polyvinyl Alcohol

Umemoto

Tanaka

Kambayashi

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to determine whether solid dispersions (SDs) are applicable to gummi formulations. Amenamevir was selected as a model of a poorly water-soluble drug, and polyvinyl alcohols (PVAs) with various degrees of hydrolysis (PVA 66, PVA 80, PVA 88, and PVA 66/88) were used as SD carriers. Design of experiments (DOE) was used to develop a gummi formulation that was suitable for an amenamevir SD using SD with PVA 66. Dissolution studies and clinical sensory tests on 11 formulations calculated by DOE revealed that a gummi formulation comprising 10.5% gelatin and 22.8% water was suitable for SD of the drug. Gummi formulations comprising amenamevir SDs with various PVAs were prepared using the determined gummi formulation, and their ability to dissolve amenamevir, their stability, and their oral absorption in dogs were evaluated. The results suggested that PVA 66, PVA 66/88, and PVA 80 were appropriate in terms of dissolution, stability, and in vivo absorption, respectively. Considering these results comprehensively, it was concluded that PVA 80, which enabled the highest degree of absorption, was the most suitable SD carrier for gummi formulations. Thus, it was possible to apply a PVA SD of amenamevir to gummi formulations.

show abstract

PBPK modeling coupled with biorelevant dissolution to forecast the oral performance of amorphous solid dispersion formulations

Cited by 35 publications

References 26 publications

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

Gummi Formulations Comprising Amenamevir Solid Dispersions with Polyvinyl Alcohol

Contact Info

Product

Resources

About