The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
Animals ; Benzofurans ; chemistry ; Biological Availability ; Cucurbitaceae ; chemistry ; Drug Carriers ; chemistry ; Drug Compounding ; Drug Stability ; Freeze Drying ; Furans ; chemistry ; Humans ; Lignans ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Male ; Nanoparticles ; administration & dosage ; chemistry ; Particle Size ; Plant Extracts ; chemistry ; isolation & purification ; Rats ; Rats, Sprague-Dawley ; Solubility

OBJECTIVE： To study the improvement effects of Lanqian buccal tablets on scopolamine-induced learning and memory impairment of mice. METHODS： The mice were randomly divided into blank group （normal saline）， model group （normal saline）， positive group （Donepezil hydrochloride tablets， 1.52 mg/kg） and Lanqian buccal tablets high-dose， medium-dose and low-dose groups （800， 400， 200 mg/kg）， with 14 mice in each group. Once a day， 30 days after continuous intragastric administration， except for blank group， other groups were intraperitioneal injected scopolamine hydrobromide 3 mg/kg to induce learning and memory impairment model. After modeling， the learning and memory ability of mice were evaluated with step through test （latency， mistake times of entering darkroom as indexes） and Morris water maze （the time of going up on the platform， the times of crossing the platform， swimming time in target quadrant as indexes）. The levels of Ach， ChAT， AchE， SOD and MDA in cerebral tissue of mice were determined. RESULTS： Compared with blank group， latency， the times of crossing the platform， swimming time in target quadrant， the levels of ChAT， Ach and SOD were shortened or decreased significantly in model group （P＜0.05 or P＜0.01）， while mistake times of entering darkroom， the time of going up on the platform， the levels of AchE and MDA were extended or rised significantly （P＜0.01）. Compared with model group， latency （except for Lanqian buccal tablet low-dose group）， the times of crossing the platform， swimming time in target quadrant， the levels of ChAT， Ach and SOD were extended or rised significantly in positive group and Lanqian buccal tablet groups （P＜0.05 or P＜0.01）. The mistake times of entering darkroom （except for Lanqian buccal tablet low-dose group）， the time of going up on the platform （except for Lanqian buccal tablet low-dose group） and the levels of AchE and MDA （except for Lanqian buccal tablet medium-dose and low-dose group） were shortened or decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Lanqian buccal tablet can improve scopolamine-induced learning and memory impairment of mice by increasing the levels of ChAT， Ach and SOD and decreasing the levels of AchE and MDA.