The elucidation of key factors for oral absorption enhancement of nanocrystal formulations: In vitro–in vivo correlation of nanocrystals

Imono, Masaaki; Uchiyama, Hiromasa; Yoshida, Saki; Miyazaki, Shiro; Tamura, Naomi; Tsutsumimoto, Hidekazu; Kadota, Kazunori; Tozuka, Yuichi

doi:10.1016/j.ejpb.2019.12.002

Cited by 32 publications

(27 citation statements)

References 32 publications

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“…Significant differences in plasma AUC following different treatments ( p < 0.05, ANOVA) proved the increased extent of absorption following nanocrystal administration. Although results of the nanocrystals’ solubility ( Figure 6 b) did not promise improved pharmacokinetics, other factors such as permeability enhancement could give rise to better absorption [ 33 ]. Moreover, the pH value of the empty and fed stomach in rats is 4–5 [ 34 ], so the solubility decrease would not be as prominent as first expected.…”

Section: Resultsmentioning

confidence: 99%

Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

et al. 2021

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Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.

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Section: Resultsmentioning

confidence: 99%

Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

et al. 2021

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“…The skin needs time to recover its barrier properties [ 232 ]. If the skin is sensitive, it can lead to mild to medium inflammation or allergies, redness, pain, swelling, and itching may cause discomfort for the patient [ 233 ]. Although the pores formed by microns in comparison to the hypodermic needle are small, microbial penetration is also less serious [ 153 ], and the pores will take time to rescreen [ 234 ].…”

Section: Pharmacokinetic and Drug Release Behavior From Polymeric Mnsmentioning

confidence: 99%

“…The production of MN-based multifunctional smart bioprocessing is still desperately needed for potential biomedical applications, considering the impressive achievements around MNs [ 139 ]. It is believed that MNs will gradually and practically progress into mass production with the advancement of science and technology, adding comfort to people’s lives [ 233 ]. Researchers expect that in the future, these MN-based smart therapeutic devices will also be more desirable if long-term usage and multi-stage medication distribution are needed for health conditions such as chronic diseases, treatment of diabetes, and chronic pain management [ 395 ].…”

Section: Current Trends and Future Perspectivementioning

confidence: 99%

Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges

Yadav

Munni²,

Campbell

et al. 2021

Pharmaceutics

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The ongoing search for biodegradable and biocompatible microneedles (MNs) that are strong enough to penetrate skin barriers, easy to prepare, and can be translated for clinical use continues. As such, this review paper is focused upon discussing the key points (e.g., choice polymeric MNs) for the translation of MNs from laboratory to clinical practice. The review reveals that polymers are most appropriately used for dissolvable and swellable MNs due to their wide range of tunable properties and that natural polymers are an ideal material choice as they structurally mimic native cellular environments. It has also been concluded that natural and synthetic polymer combinations are useful as polymers usually lack mechanical strength, stability, or other desired properties for the fabrication and insertion of MNs. This review evaluates fabrication methods and materials choice, disease and health conditions, clinical challenges, and the future of MNs in public healthcare services, focusing on literature from the last decade.

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“…Nanosuspension with narrow distributions of particles produced systems with improved absorption, less variability, and superior stability by minimizing the Ostwald ripening process. Imono et al (2020) prepared microsuspensions of two model drugs, namely, fenofibrate and megesterone acetate, along with three nanosuspensions with various particle sizes. Through in vitro dissolution-permeation studies and in vivo oral pharmacokinetic studies, it was found that the particle size reduction only slightly increased the apparent solubilities (1.4 times) but significantly increased the penetration rates of the two drugs (3 times).…”

Section: In Vitro and In Vivo Drug Release Studiesmentioning

confidence: 99%

Progress in the development of stabilization strategies for nanocrystal preparations

Wang

Zhang

et al. 2020

Drug Delivery

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In recent years, nanocrystal technology has been extensively investigated. Due to the submicron particle size and unique physicochemical properties of nanocrystals, they overcome the problems of low drug solubility and poor bioavailability. Although the structures of nanocrystals are simple, the further development of these materials is hindered by their stability. Drug nanocrystals with particle sizes of 1∼1000 nm usually require the addition of stabilizers such as polymers or surfactants to enhance their stability. The stability of nanocrystal suspensions and the redispersibility of solid nanocrystal drugs are the key factors for the large-scale production of nanocrystal preparations. In this paper, the factors that affect the stability of drug nanocrystal preparations are discussed, and related methods for solving the stability problem are put forward.

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The elucidation of key factors for oral absorption enhancement of nanocrystal formulations: In vitro–in vivo correlation of nanocrystals

Cited by 32 publications

References 32 publications

Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

Overcoming the Low Oral Bioavailability of Deuterated Pyrazoloquinolinone Ligand DK-I-60-3 by Nanonization: A Knowledge-Based Approach

Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges

Progress in the development of stabilization strategies for nanocrystal preparations

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