The use of amphiphilic copolymer in the solid dispersion formulation of nimodipine to inhibit drug crystallization in the release media: Combining nano-drug delivery system with solid preparations

Wei, Minyan; Lei, Xueping; Fu, Jingjing; Chen, Mingyue; Li, Jie-xia; Yu, Xiyong; Lin, Yi; Liu, Jingping; Du, Lingran; Li, Xin; Miao, Yingling; Huang, Yugang; Liang, Lu; Fu, Jijun

doi:10.1016/j.msec.2020.110836

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…Our previous work demonstrated that the Tg of Soluplus could increase with the addition of PVP/VA 64, which could effectively slow down the aging of solid dispersions. 21 Herein, NOB/SDs were further optimized by different ratios of NOB/soluplus/PVP/VA 64. The results in Figure 2D indicated that NOB/SD exhibited a high supersaturation of NOB for 6 h (88 μg/mL) with a NOB/soluplus/PVP/VA 64 ratio of 1:5:1.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, solid dispersions of nimodipine were successfully prepared by hot melt extrusion technology using Soluplus and PVP/VA 64 as carriers. 21 Interestingly, solid dispersion of nimodipine improved the solubility and bioavailability of nimodipine with Soluplus/PVP/PV 64-based micelles constructed in aqueous media. Thus, solid dispersion may be an effective strategy for enhancing the solubility of NOB.…”

Section: Introductionmentioning

confidence: 99%

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The Self-Assembly Soluplus Nanomicelles of Nobiletin in Aqueous Medium Based on Solid Dispersion and Their Increased Hepatoprotective Effect on APAP-Induced Acute Liver Injury

Ning,

Zheng,

Cai

et al. 2023

IJN

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Purpose APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy. Methods The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo. Results NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Conclusion These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Self-Assembly Soluplus Nanomicelles of Nobiletin in Aqueous Medium Based on Solid Dispersion and Their Increased Hepatoprotective Effect on APAP-Induced Acute Liver Injury

Ning,

Zheng,

Cai

et al. 2023

IJN

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“…Investigation of NMD chemical structure and its polymorphism by 1 H NMR and 13 C NMR has been previously reported by several studies. 42,43 Comparing the NMR spectra of NMD powder and NMD 40% before and after sterilization (Figure 6), it can be seen that the important peaks arising from NMD 43 are which proves the nimodipine stability during the production and the sterilization process. As it was expected for the starch, the peaks of starch can be seen in both samples.…”

Section: Nmr Spectroscopymentioning

confidence: 97%

Characterization of Controlled Release Starch-Nimodipine Implant for Antispasmodic and Neuroprotective Therapies in the Brain

Esfahani,

Trutschel,

Reichert

et al. 2023

Mol. Pharmaceutics

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Parenteral depot systems can provide a constant release of drugs over a few days to months. Most of the parenteral depot products on the market are based on poly(lactic acid) and poly(lactide-co-glycolide) (PLGA). Studies have shown that acidic monomers of these polymers can lead to nonlinear release profiles or even drug inactivation before release. Therefore, finding alternatives for these polymers is of great importance. Our previous study showed the potential of starch as a natural and biodegradable polymer to form a controlled release system. Subarachnoid hemorrhage (SAH) is a life-threatening type of stroke and a major cause of death and disability in patients. Nimotop® (nimodipine (NMD)) is an FDA-approved drug for treating SAH-induced vasospasms. In addition, NMD has, in contrast to other Ca antagonists, unique neuroprotective effects. The oral administration of NMD is linked to variable absorption and systemic side effects. Therefore, the development of a local parenteral depot formulation is desirable. To avoid the formation of an acidic microenvironment and autocatalytic polymer degradation, we avoided PLGA as a matrix and investigated starch as an alternative. Implants with drug loads of 20 and 40% NMD were prepared by hot melt extrusion (HME) and sterilized with an electron beam. The effects of HME and electron beam on NMD and starch were evaluated with NMR, IR, and Raman spectroscopy. The release profile of NMD from the systems was assessed by high-performance liquid chromatography. Different spectroscopy methods confirmed the stability of NMD during the sterilization process. The homogeneity of the produced system was proven by Raman spectroscopy and scanning electron microscopy images. In vitro release studies demonstrated the sustained release of NMD over more than 3 months from both NMD systems. In summary, homogeneous nimodipine-starch implants were produced and characterized, which can be used for therapeutic purposes in the brain.

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“… 10 , 11 In the microspheres system, poorly water-soluble drugs are disseminated in hydrophilic excipients giving spherical shape with micrometre size. 12 Microspheres are produced by utilising various methods such as spray-drying and hot melt extrusion. 13 , 14 The former method is prepared by dissolving/suspending drugs and ingredients in proper solvent.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres

Kim¹,

Din²,

Lee³

et al. 2021

IJN

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Background The purpose of this study was to screen various drug delivery systems for improving the aqueous solubility and oral bioavailability of sildenafil. Three representative techniques, solid self-nanoemulsifying drug delivery systems (SNEDDS), amorphous microspheres and crystalline microspheres, were compared. Methods Both microspheres systems contained sildenafil:Labrasol:PVP at a weight ratio of 1:1:6. The amorphous microspheres were manufactured using ethanol, while crystalline microspheres were generated using distilled water. Liquid SNEDDS was composed of sildenafil:Labrasol:Transcutol HP:Captex 300 in the ratio of 1:70:15:15 (w:w:w:w). The solidification process in SNEDDS was performed using HDK N20 Pharma as a solid carrier. Results The amorphous microspheres appeared spherical with significantly decreased particle size compared to the drug powder. The crystalline microspheres exhibited a rough surface with no major particle-size difference compared with sildenafil powder, indicating that the hydrophilic excipients adhered to the sildenafil crystal. Solid SNEDDS presented a smooth surface, assuming that the oily liquid was adsorbed to the porous solid carrier. According to the physicochemical evaluation, the crystalline state maintained in crystalline microspheres, whereas the crystal state changed to amorphous state in other formulations. Amorphous microspheres, crystalline microspheres and solid SNEDDS produced about 79, 55, 82-fold increased solubility, compared to drug powder. Moreover, the prepared formulations provided a higher dissolution rate (%) and plasma concentration than did the drug powder (performance order; solid SNEDDS ≥ amorphous microspheres ≥ crystalline microspheres > drug powder). Among the formulations, solid SNEDDS demonstrated the highest improvement in oral bioavailability (AUC; 1508.78 ± 343.95 h·ng/mL). Conclusion Therefore, solid SNEDDS could be recommended as an oral dosage form for enhancing the oral bioavailability of sildenafil.

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The use of amphiphilic copolymer in the solid dispersion formulation of nimodipine to inhibit drug crystallization in the release media: Combining nano-drug delivery system with solid preparations

Cited by 11 publications

References 21 publications

The Self-Assembly Soluplus Nanomicelles of Nobiletin in Aqueous Medium Based on Solid Dispersion and Their Increased Hepatoprotective Effect on APAP-Induced Acute Liver Injury

The Self-Assembly Soluplus Nanomicelles of Nobiletin in Aqueous Medium Based on Solid Dispersion and Their Increased Hepatoprotective Effect on APAP-Induced Acute Liver Injury

Characterization of Controlled Release Starch-Nimodipine Implant for Antispasmodic and Neuroprotective Therapies in the Brain

Comparison of Three Different Aqueous Microenvironments for Enhancing Oral Bioavailability of Sildenafil: Solid Self-Nanoemulsifying Drug Delivery System, Amorphous Microspheres and Crystalline Microspheres

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