Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

Abstract

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug “Tianma” (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

“…The effective dosage we demonstrated for anti-hypertrophic action, which was 50 mg/kg/day in mice, equivalent to 4 mg/kg/day in human based on the conversion factor of 12.3 ( Nair and Jacob, 2016 ), is within the clinical dosage for neurological disease treatment (200–600 mg/day per adult, or 3.3 – 10 mg/kg/day based on body weight of 60 kg) ( Huang, 1985 ; Nair and Jacob, 2016 ). In cultured cardiomyocyte model, we used 100 μM gastrodin, which is also near the range of the plasma gastrodin concentration of mice injected with 200 mg/kg gastrodin (with the peak plasma concentration of 500 μM gradually declined to 150 μM 3 h after the injection) ( Cai et al, 2014 ). This should greatly enhance the potential of using gastrodin as a future anti-hypertrophic agent.…”

Borneol, a novel agent that improves central nervous system drug delivery by enhancing blood–brain barrier permeability

“…Borneol and gastrodin co-loaded sustained-release solid dispersions were prepared using ethylcellulose as a sustained-release matrix and hydroxy-propyl methylcellulose as a retarder. Sustained-release technology appears to be an effective approach to minimizing stomach irritation while preserving sufficient transport capacity for brain-targeted delivery of orally administered borneol (Cai et al, 2014).…”

“…The co-loading of borneol and gastrodin, a principal bioactive ingredient of the Chinese herbal medicine Rhizoma Gastrodiae (Tian-Ma), into sustained-release solid dispersions can largely reduce gastric mucosal irritation caused by borneol without sacrificing its targeting efficiency (Cai et al, 2014). Borneol and gastrodin co-loaded sustained-release solid dispersions were prepared using ethylcellulose as a sustained-release matrix and hydroxy-propyl methylcellulose as a retarder.…”

Current Strategies for Brain Drug Delivery

“…The authors proposed further studies on doses, schedules and combination regimens. Recently, borneol has been studied to increase both oral absorption and brain penetration of drugs in animal models 63 - 65 . Yi et al compared four different oral formulations of puerarin with borneol.…”