Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

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Development of novel darunavir amorphous solid dispersions with mesoporous carriers

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2021.105700 ◽

2021 ◽

Vol 159 ◽

pp. 105700

Author(s):

Sergey A. Zolotov ◽

Natalia B. Demina ◽

Anna S. Zolotova ◽

Natalia V. Shevlyagina ◽

Grigorii A. Buzanov ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Amorphous Solid Dispersions

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Effect of Carrier Type and Tween® 80 Concentration on the Release of Silymarin from Amorphous Solid Dispersions

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2021.102416 ◽

2021 ◽

pp. 102416

Author(s):

Valentyn Mohylyuk ◽

Thomas Pauly ◽

Oleksandr Dobrovolnyi ◽

Nathan Scott ◽

David S. Jones ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Amorphous Solid Dispersions

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Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽

10.3390/antiox10010090 ◽

2021 ◽

Vol 10 (1) ◽

pp. 90

Author(s):

Eun-Sol Ha ◽

Du Hyung Choi ◽

In-hwan Baek ◽

Heejun Park ◽

Min-Soo Kim

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Solid Dispersions ◽

Amorphous Solid ◽

Pharmaceutical Products ◽

In Vitro Dissolution ◽

Dependent Manner ◽

Amorphous Solid Dispersions ◽

Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

International Journal of Molecular Sciences ◽

10.3390/ijms22052479 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2479

Author(s):

Amir Mohammadzadeh ◽

Péter P. Lakatos ◽

Mihály Balogh ◽

Ferenc Zádor ◽

Dávid Árpád Karádi ◽

...

Keyword(s):

Neuropathic Pain ◽

Animal Studies ◽

Acute Administration ◽

Pain Model ◽

Therapeutic Value ◽

Small Doses ◽

Function Test ◽

Neuropathic Pain Model ◽

First Time ◽

Glycine Content

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.

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