ABSTRACT
Objective: To prepare glycyrrhizic acid (GL)-Pluronic F127 (F127)/polyethylene glycol 1000 vitamin E succinate (TPGS) mixed nanomicelles (MMs) and improve oral absorption of GL. Methods: GL-F127/TPGS-MMs was prepared by thin film dispersion method. The encapsulation efficiency and drug loading of MMs were used as evaluation indexes. The formulation and process, including the ratio of F127 to TPGS, the concentration of polymer and GL, hydration temperature and time, were optimized by the single factor experiment. The morphology of MMs was investigated by transmission electron microscopy. The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of GL-F127/TPGS-MMs with absorption rate constant (Ka) and apparent absorption coefficient (Papp) as evaluation indexes. Results: The optimal formulation and process of GL-F127/TPGS-MMs were as follows: TPGS 180 mg, F127 270 mg, GL 70 mg, hydration temperature 50 ℃ and hydration time 3 h. The prepared GL-F127/TPGS-MMs had good clarity and the particle size, polydispersity index, and Zeta potential were (28.20 ± 5.63) nm, 0.20 ± 0.06, and (-5.24 ± 1.55) mV, respectively. The encapsulation efficiency and drug loading were (97.57 ± 5.29) % and (13.13 ± 0.71) %, respectively. The MMs were spherical with distinct vesicle structure. The absorption of GL in the jejunum segment was significantly higher than that in the ileum segment (P < 0.05). Compared with raw GL, GL-F127/TPGS-MMs had a statistically significant higher absorption rate in the intestinal segment (P < 0.05). Conclusion: The prepared GL-F127/TPGS-MMs could significantly improve the absorption of GL in vivo.
ABSTRACT
Aim To prepare evodiamine butyryl deriva-tive (EBD) and evodiamine butyryl derivative-loaded solid lipid nanoparticles (EBDLN), and study its re-lease in vitro,and to investigate its in situ gastrointesti-nal absorption. Methods EBD was prepared by a one-step synthetized method, and then EBDLN was prepared by a film dispersion method. Dynamic dialy-sis was used to evaluate drug release in vitro,and sin-gle-pass gastrointestinal perfusion was employed to study the gastrointestinal absorption of EDM,EBD and EBDLN. Results In identical release media, there were identical drug release tendencies of EBD and EB-DLN, but the release rate of EBDLN was faster than EBD. Compared with EDM and EBD, the Kavalues and Pappvalues of EBDLN in every perfusion segment increased significantly. The Kaof EBDLN in stomach, duodenum, jejunum, ileum and colon was 110.14-fold,56.70-fold,51.23-fold,45.70-fold and 127.23-fold of free EDM respectively. The Pappvalue of EB-DLN was 9.74-fold, 4.48-fold, 3.82-fold and 11.3-fold of that of free EDM. Conclusion EBDLN has sustained effect and can enhance the gastrointestinal absorption of EDM and EBD.
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Objective: To compare intestinal absorption features of berberine hydrochloride phospholipid solid dispersions (BBH-PSD) by rat single-pass perfusion model, and to explore the mechanism of berberine bioavailability increasing mechanism by phospholipid solid dispersion technology. Methods: The single-pass perfusion model was established in rats, the concentration of berberine in intestinal perfusion was determined by HPLC, and phospholipid solid dispersion technology promoting intestinal absorption of berberine was investigated. Results: Compared with berberine, BBH-PSD could promote much more absorption of berberine in various intestinal segments, especially in jejunum, and the mechanism was related to improving permeability and strengthen simple diffusion of berberine. The Ka and Papp values of BBH and BBH-PSD in jejunum were obviously higher than BBH (P < 0.05); When the volumetic flow rate of BBH-PSD was 0.2, 0.4, and 0.8 mL/min, Ka and Papp were both higher than BBH (P < 0.05); The increasing mass concentration was not obvious to intestinal absorption of BBH, while the increasing mass concentration of BBH-PSD obviously increased the intestinal absorption of BBH (P < 0.05). Conclusion: Intestinal absorption characteristics of berberine phospholipid solid dispersion is beneficial to improve berberine oral bioavailability, and it can provide a scientific basis for the development of new dosage forms of berberine hydrochloride.
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AIM: To investigate the nasal absorption of ligustrazine and promotion action of synthetic borneol. METHODS: In situ nasal recirculation method was used to study the dose effect relationship of nasal absorption of ligustrazine and the effect of synthetic borneol on nasal absorption of ligustrazine in rats. RESULTS: When the concentrations of ligustrazine were 0.25 , 0.75 ,and 1.25 g?L -1 in circulation liquid, respectively, the corresponding values of the absorption rate constant k were 0.0195 , 0.0227 , and 0.0241 min -1 . However, when the concentrations were 2.5 and 5.0 g?L -1 in circulation liquid, the absorption rate constant k lowered with the concentration being added. CONCLUSION: Ligustrazine can be absorbed through the nasal mucous and synthetic borneol can promote the absorption.
ABSTRACT
Objective To study the characteristic of in-vivo nasal mucosa absorption of tetramethylpyrazine phosphate(TMPP) liposome in rats. Methods Nasal circulatory perfusion method in rats was used to study the effects of different circulatory rates and TMPP concentrations on nasal mucosa absorption of TMPP liposome. Nasal mucosa absorption rate constants of TMPP liposomes and TMPP solutions at the same concentration were also compared. Results The absorption rate constant of TMPP liposomes was increased with the increase of circulatory rates at the range of 1.2～2.4 mL/min and with the increase of TMPP concentrations at the range of 0.245～0.98 mg/mL. Both the absorption rate constant and absorbed amount of TMPP for TMPP liposomes were higher than those for TMPP solutions at the same concentration. Conclusion The nasal mucosa absorption of TMPP liposome was complete as compared with that of TMPP solution.