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(H...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 2015 J. 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 AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.展开更多
Herpetospermum caudigerum lignans(HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability...Herpetospermum caudigerum lignans(HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione(HPE) and herpetin(HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL(composed of HPE and HPN) nanosuspensions(HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4%(W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 oC for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC0–t, C_(max), MRT and a decrease in T_(max), compared to the raw drug.. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with p H-dependent solubility.展开更多
基金financially supported by the National Key New Drugs Innovation Foundation(No.2016X09101073)the National Natural Science Foundation of China(No.81573697)
文摘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 2015 J. 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 AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
基金supported by the National Key New Drugs Innovation Foundation(No.2015ZX09101025)the National Science Foundation of China(No.81503169)the New Drugs Development Special Foundation of Beijing City of China(No.Z141100002214007)
文摘Herpetospermum caudigerum lignans(HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione(HPE) and herpetin(HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL(composed of HPE and HPN) nanosuspensions(HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4%(W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 oC for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC0–t, C_(max), MRT and a decrease in T_(max), compared to the raw drug.. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with p H-dependent solubility.
