Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Preparation of Angelica•Cinnamomum self•microemulsion drug delivery system based on the concept of “unifica- tion of drugs and excipients ” / 中国药房

OBJECTIVE To prepare Angelica•Cinnamomum（Angelica sinensis-Cinnamomum cassia ）self•microemulsion drug delivery system （AC•SMEDDS），and to optimize its formulation and characterize its preparation . METHODS Using Angelica• Cinnamomum mixed volatile oil as oil phase and model drug ，on the basis of selecting emulsifier and co -emulsifier and the optimization of their mass ratio range ，the formulation was optimized with central composite design •response surface methodology using the ratio of oil phase （Angelica•Cinnamomum mixed volatile oil ），mass ratio of emulsifier and co -emulsifier as factors ，the comprehensive score of volatile oil content ，particle size and emulsifying time as index . Morphology，particle size ，drug loading ， entrapped efficiency and stability of optimized AC•SMEDDS were characterized . RESULTS The optimum formulation of AC•SMEDDS contained the ratio of oil phase was 30%，and the mass ratio of emulsifier （EL•40）and co -emulsifier（ethanol）was 9∶1. Results of validation tests showed that the average particle size of AC•SMEDDS was （148.33±1.53）nm，and emulsifying time was （18.44±0.11）s. The comprehensive score was 0.68，relative deviation of which from the predicted value （0.70）was 2.86%. AC•SMEDDS prepared by optimal formulation was faint yellow ，uniform and transparent liquid ，and spherical particals with translucent edge were observed under transmission electron microscope . Calculated by ligustilide and cinnamaldehyde ，the drug loading was （7.58±0.03） and （4.17±0.01） mg/g，and entrapped efficiency was （93.25±0.01）% and （88.89±0.02）% ， respectively. No stratification or precipitation occurred after centrifugation at the speed of 10 000 r/min or placing within 7 （No.2019-0520） days at 4 and 25 ℃ . The contents of ligustilide and cinnamaldehyde were stable . Its particle size had no significant change after 50，100 and 200 times dilution by purified water . CONCLUTIONS AC•SMEDDS is prepared successfully and its formulation is optimized . The stability of the preparation is good .

Preparation, quality evaluation and cell uptake of 1,8-cineole self-microemulsion drug delivery system / 中草药

Objective: To optimize the formulation of 1,8-cineole self-microemulsifying drug delivery system (1,8-Cin-SMEDDS), characterize it and investigate its cell uptake. Methods: By drawing pseudo-ternary phase diagram, the effective self-emulsifying region of 1,8-Cin-SMEDDS was determined, and the preliminary prescription was screened. Taking the particle size and drug loading as the index, the central composite design-response surface method was used to optimize and verify the prescription. Fluorescence microscope was used to observe the uptake of human umbilical vein endothelial cells (HUVEC) injured by high glucose. Results: The results showed that the best prescription of 1,8-Cin-SMEDDS was a mixture of soybean oil (7.5%) and 1,8-Cin (22.5%), HS15 (56%) as emulsifier, ethanol (14%) as co-emulsifier, and dripping pure water to 8 mL to obtain a translucent slightly bluish emulsion. The appearance of spherical droplets was observed by transmission electron microscope, and the average particle size and Zeta potential measured by laser particle size Zeta tester was (131.68 ± 1.44) nm and (-10.03 ± 1.63) mV, respectively; The entrapment efficiency estimated by HPLC was (99.890 ± 0.012)%, and the drug loading was (224.750 ± 0.028) mg/g. The results of HUVEC cell uptake assay showed that the uptake of 1,8-Cin-SMEDDS by cells was higher than that of free 1,8-Cin. Conclusion: The preparation method of 1,8-Cin-SMEDDS is simple and reproducible. The obtained method has good appearance, high entrapment efficiency, stable physical, and chemical properties, which can also promote cell uptake.

Preparation of self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase / 中草药

Objective: To prepare the self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase. Methods: M. haplocalyx oil was used as the oil phase, and C. tinctorius extract was used as the water phase. The prescription of self-microemulsion were optimized by pseudo-ternary phase diagram, the process and prescription of gel were screened by single-factor method and the appearance, viscosity and pH value were evaluated. Result: The optimal formulation of CTE-SMEDDS-BGs was as following: F68 was the emulsifier, anhydrous ethanol was the co-emulsifier, the Km ratio was 1:1, and the total amount of emulsifier and co-emulsifier to M. plocalyx oil was 8:2, carbopol-980 was 2%, glycerin was 6%, and C. tinctorius extract was 5 mL. The CTE-SMEDDS-BGs was obtained by adding the CTE-SMEDDS into swelling gel matrix and triethylamine was used to adjust the pH to 6.0. The characteristics of appearance were yellow translucent, moderate viscosity, uniform and delicate, non-greasy, and easy to spread on the skin, the viscosity was 4.98 × 104 mPa•s (RSD was 1.53%), pH was 6.04 (RSD was 0.44%). Conclusion: The CTE- SMEDDS-BGs with M. plocalyx oil as oil phase is simple and stable, and meets the requirements of gel topical preparations.

Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and β-asarone / 中国中药杂志

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.

Preparation and in vitro quality evaluation of silybin supersaturated self-microemulsion drug delivery system / 中草药

Objective: To develop and optimize the silybin supersaturated self-microemulsion drug delivery system (SLB-SSMEDDS) and improve the oral bioavailability of SLB in the biological medium. Methods: The formulation of SLB-SMEDDS was selected by solubility test, emulsifying ability of emulsifier and pseudo-ternary phase diagram. The analytic hierarchy process (AHP) was used to evaluate the performance of each prescription to screen the optimal ratio. The type and dosage of precipitation inhibitors (PPIs) was optimized to maintain the supersaturation and duration of drugs in biological media in vitro; Finally, the emulsification effect, emulsion size and surface morphology of SLB-SSMEDDS was comprehensively evaluated in terms of in vitro release and in vitro supersaturation. Results: The SLB-SSMEDDS prescription was Capryol 90-Cremophor RH-Transcutol HP-HPMC-AS MF (10:67.5:22.5:2). The self-microemulsion with a drug loading of 50.19 mg/g was uniform and the emulsion droplets were spherical in shape and uniform in size. And the emulsification time was (30.67 ± 4.16) s, the average particle size was (11.67 ± 0.81) nm, and the PDI was (0.15 ± 0.04). The dissolution rate of SLB-SSMEDDS in FaSSGF and FaSSIF-V2 was significantly increased. And the in vitro dilution and supersaturation could be maintained above 10 within 120 min. Conclusion: SLB-SSMEDDS has a simple preparation process and can improve the stability of traditional SMEDDS, maintain supersaturation effectively and enhance the dissolution of SLB in vitro.

Formulation Optimization and Quality Evaluation of Usnic Acid Self-microemulsion / 中国药房

OBJECTIVE: To prepare Usnic acid self-microemulsion, prescription optimization and evaluate its quality. METHODS: Usnic acid self-microemulsion was prepared by emulsification method using medium chain triglycerides-single linoleic acid glyceride (1:1, m/m) as oil phase, polyoxyethylene hydrogenated castor oil as emulsifier, diethylene glycol monoethyl ether as co-emulsifier. Based on the solubility test and pseudotemary phase diagram, using self-emulsifying time (t), light transmittance (T), drug equilibrium solubility (S), accumulative dissolution rate at 5 min and 60 min (Q5 min, Q60 min) as evaluation indexes, central composite design-response surface methodology was utilized to optimize oil phase ratio and ratio of emulsifier to co-emulsifier (Km) in microemulsion formulation. At the same time, the optimal formulation was verified, the morphology, particle size, drug-loading amount and dissolution of Usnic acid self-microemulsion were investigated. RESULTS: The optimal formulation was as follows as oil phase ratio of 25％, Km of 2. 0; ratio of mixed oil phase, emulsifier, co-emulsifier in the formulation was 25％, 50％, 25％. t, T, S, Q5 min and Q60 min of Usnic acid self-microemulsion prepared by optimal formulation were 1. 96 min, 87. 67％, 5. 67 mg/g, 66. 58％, 76. 73％ (all RSD<3％, n = 3),respectively. The relative errors of them to predicted values were all less than 4％ (n = 3). Usnic acid self-microemulsion was spherical droplet in shape after diluted with water. The average particle size was 39. 4 nm, average drug-loading amount was 4. 55 mg/g. Q90 min of Usnic acid self-microemulsion reached 99. 58％ in pH 6. 8 phosphate buffer (n = 3). CONCLUSIONS: Prepared Usnic acid self-microemulsion is in line with quality requirements.

Pharmacokinetic and Bioavailability Study of Aspirin Phospholipid Complex Self-microemulsion in Rats in vivo / 中国药房

OBJECTIVE:To study the pharmacokinetics behaviors and the bioavailability of aspirin phospholipid complex self-microemulsion in rats in vivo. METHODS:12 SD rats were randomly divided into aspirin suspension group(10 mg/kg)and as-pirin phospholipid complex self-microemulsion group (10 mg/kg),6 in each group. Rats were intragastrically administrated,and blood sample 0.6 mL was taken from jugular vein before administration and after 0.083,0.25,0.5,0.75,1.0,2.0,3.0,4.0,6.0, 8.0,12.0 h of administration. HPLC was used to determine the concentration of salicylic acid in rats'plasma. DAS 2.0 pharmacoki-netic software was adopted to calculate the pharmacokinetic parameters and relative bioavailability. RESULTS:The pharmacokinetic processes of both aspirin suspension and aspirin phospholipid complex self-microemulsion were in line with one-compartment mod-el. The salicylic acid of cmax of rats in aspirin suspension group and aspirin phospholipid complex self-microemulsion group were (1.904 ± 0.208),(6.457 ± 1.091) μg/mL;AUC0-12 h were (12.860 ± 1.327),(47.270 ± 12.860) μg/(h·mL);tmax were (2.167 ± 0.983),(0.917±0.540)h,respectively. Compared with aspirin suspension,salicylic acid of cmax and AUC0-12 h of aspirin phospholip-id complex self-microemulsion in rats in vivo were significantly increased (P<0.01),while tmax was significantly decreased (P<0.05);the relative bioavailability was 367.57%. CONCLUSIONS:Making aspirin into phospholipid complex self-microemulsion can improve the gastrointestinal absorption,with high relative bioavailability.

Effect of Natural Emulsifier Acacia Senegal on in vivo and in vitro Performance of Chlorogenic Acid Self-microemulsion / 中国药房

OBJECTIVE:To study the effect of natural emulsifier acacia senegal on in vivo and in vitro performance of chloro-genic acid self-microemulsion. METHODS:Chlorogenic acid self-microemulsion containing acacia senegal(new chlorogenic acid self-microemulsion)was prepared by using acacia senegal to gradually replace polysorbate 80 in chlorogenic acid self-microemul-sion containing nonionic emulsifier (traditional chlorogenic acid self-microemulsion). The appearance,morphology,particle size,conductivity,pH value,stability,in vitro release and intestinal absorption kinetics of the 2 kinds self-microemulsions were evaluated. RESULTS:50％of polysorbate 80 was replaced by acacia senegal in new chlorogenic acid self-microemulsion. The tradi-tional and new chlorogenic acid self-microemulsions had clear appearance,and approximately spherical drops. Particle sizes were (24.53 ± 3.03),(35.51 ± 5.91) nm;dectrical conductivities were (195.6 ± 0.3),(189.5 ± 0.4)μs/cm;and pH were 3.87 ± 0.02, 4.08 ± 0.03 (n=3),respectively. Compared with traditional chlorogenic acid self-microemulsion,the absorption rate constant,ef-fective permeability coefficient and absorption amount of the new one in duodenum,jejunum,ileum were increased a little (P>0.05);the above indexes in colon were obviously decreased (P<0.05). CONCLUSIONS:The new chlorogenic acid self-micro-emulsion can maintain the performance of traditional one,and increase absorption of chlorogenic acid in small intestine.

Construction of ginkgo flavonoids drug release system / 中草药

Objective: To construct ginkgo flavonoids drug release system based on bioavailability of ginkgo flavonoids and its clinical drug delivery behavior. Methods: Suitable oil phase, surfactant and cosurfactant were selected according to the solubility; Suitable Km value (ratio of surfactant to cosurfactant) based on the pseudo-ternary phase diagram was selected by water titration; Further prescription studies were performed at the selected Km value; The microemulsion dose was determined by HPLC; The self-microemulsion was made according to the prescription, and then the appropriate materials were added to make pellets; The preparation of pellets was evaluated. Results: Isopropyl myristate (IPM), Tween 80 and anhydrous ethanol were selected as oil phase, surfactant and cosurfactant; The Km value was 3:1; The ratio of total quality of Tween 80 and absolute ethanol to IPM was 9:1; The size of particle was less than 30 nm; Drug loading was 13.32 mg/mL. Conclusion: The pellets are stable using microemulsion as the former preparation, which improve the bioavailability of flavonoids.

Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (<0.01). The absorption rate constant () and the apparent permeability coefficient () for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values ofandof Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration () of the blocking model were significantly lower than those of the control model (<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

Optimization of Self-microemulsion Containing Total Saponins from Lysimachia capillipes by Central Composite Design-response Surface Methodology / 中国药学杂志

OBJECTIVE: To optimize the formulation of self-microemulsion containing total saponins from Lysimachia capillipes by central composite design-response surface methodology. METHODS: Based on the study of solubility, compatibility test and ternary phase diagram, central composite design-response surface methodology was adopted to optimize the best prescription with the emulsifying time, particle size, and Zeta pontential as indexes, physicochemical properties of this self-microemulsion were also determined. RESULTS: Optimum formulation was 12.93% of ethyl oleate, 57.25% of Kolliphor RH40, 29.82% of Transcutol. The a verage particle size, polydispersity index, Zeta pontential and drug loading of self-microemulsion containing total saponins from Lysimachia capillipes were 23.0 nm, 0.160, -20.28 mV and 10.52 mg·g-1.CONCLUSION: With good predictability, this methods can be used for the formulation optimization of self-microemulsion loaded total saponins from Lysimachia capillipes.

Effects of different preparation technologies on concentrations of puerarin and catalpol in plasma and brain of rats after oral administration / 中国中药杂志

To compare the effects of different preparation technologies on the concentrations of puerarin and catalpol in plasma and brain of rats after oral administration, in order to lay an experimental basis for developing new oral Zige preparations. The nanocrystal, self-microemulsions (tween-80 and Cremophor RH-40 as emulsifiers) and inclusion complex of HP-β-CD containing puerarin and catalpol were prepared. The concentrations of puerarin and catalpol in plasma and brain of rats after oral administration were determined by HPLC-MS/MS method. The pharmacokinetic parameters and brain target index were compared. The results showed that preparation technologies had different influences on the concentrations of puerarin and catalpol in plasma and brain. The self-microemulsion (tween-80) could significantly increase the oral absorption of puerarin than other technologies(P<0.05), and inclusion complex could remarkably increase the oral absorption of catalpol than nanocrystal(P<0.01). For puerarin, the brain targeting index of inclusion complex was the highest (P<0.05); but for catalpol, the brain targeting index of inclusion complex and self-microemulsions were both higher than nanocrystal (P<0.05). The self-microemulsion(tween-80) had the highest AUCbrain of puerarin than other groups (P<0.01); the inclusion complex had the highest AUCbrain for catalpol, but there was no significant difference compared with self-microemulsions. In conclusion, the self-microemulsion (tween-80) technology could increase the amount of puerarin and catalpol in brain, and was expected to be used in new oral Zige preparations.

Study on the Hypoglycemic Effect of Insulin Self-microemulsion for Parenteral Administration / 中国药房

OBJECTIVE:To study the hypoglycemic effects of Insulin self-microemulsion for parenteral administration on mod-el rats with type 1 diabetes in vivo. METHODS:Rats were treated with streptozotocin(50 mg/kg)to reproduce model with type 1 diabetes,ip. The model rats were randomly divided into model group (normal saline),positive control group (Insulin injection 2.25 u/kg) and self-microemulsion low,medium and high dose groups (Insulin self-microemulsion 4.5,9 and 18 u/kg);and 10 normal rats were involved in sham-operation group (normal saline). Anesthesia and operation were conducted for all rats. Positive control group was administrated,ip;other rats were parenterally administrated. The blood glucose levels in groups were detected be-fore and after 15-600 min administration. Glucose tolerance test was conducted for the rats in normal control group,model group without glucose,model group with glucose and microemulsion group (Insulin self-microemulsion 9 u/kg). All group were given glucose except model group without glucose. RESULTS:Compared with sham-operation group,the blood glucose levels in model group within 0-240 min were increased,with significant difference(P<0.05). Compared with model group,there was hypoglyce-mic trend in positive control group after 15 min,the blood glucose levels within 30-480 min were decreased,the hypoglycemic peak was 36%,and the peak time was 30 min;there was also hypoglycemic trend in microemulsion low,medium and high dose groups after 30 min,the blood glucose levels within 45-360 min were decreased,hypoglycemic peak was 18%-21%,and the peak time was 90-120 min,with significant differences (P<0.01 or P<0.05). All rats had glucose absorption peak except for model group without glucose in glucose tolerance test,and glucose of rats in microemulsion group reached its peak and then quickly de-creased. CONCLUSIONS:Insulin self-microemulsion can obviously reduce the blood glucose of model rats with type 1 diabetes.

Preparation technology of supersaturatable self-microemulsifying drug delivery system of etoposide and quality evaluation / 中草药

To prepare supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) of etoposide (VP-16) for increasing the solubility of difficult soluble drug of etoposide, which will provide a scientific basis for improving its bioavailability. To study the prescription and preparation technology of S-SMEDDS of VP-16, according to different oil phases, compatibility of surfactants, and the microemulsion area size in the pseudo ternary phase diagram of different cosurfactants, to determine the basic prescription of self-microemulsifying concentrate, optimize the prescription of VP-16 based on its solubility and crystallization conditions, with filtrating appropriate precipitation inhibitor and the best prescription drug loading. The rate of self-microemulsifying was taken as index to study the preparation technology of VP-16 S-SMEDDS for investigating the influence on the ability of self-microemulsifying. The optimal prescription is: RH40-PEG 400-GTCC-PVP K30 (20∶ 20∶ 10∶ 1), 2% drug content of the mass fraction. The optimum technological conditions are 37 ℃, 20 r/min, and 20 min by magnetic stirring. The average particle size of VP-16 S-SMEDDS is (82.7 ± 3.3) nm and the size distribution of VP-16 S-SMEDDS is relatively concentrated. The average content of VP-16 in three batches of S-SMEDDS is 19.98 mg/g. Results of dissolution test showed that at 60 min the cumulative dissolution is close to 100%. Stability study results show that the high temperature and light could influence the drug stability and micro emulsification ability of VP-16 S-SMEDDS, while the psychro-thermal cycles test has no influence to it. After the preliminary stability test, the results show that the stability of VP-16 S-SMEDDS is good. The optimized prescription of VP-16 S-SMEDDS can significantly increase the solubility of VP-16, and it's quality is stable, which could improve its bioavailability further. The research method is scientific, reliable, and feasible.

Pharmacokinetic Study of Puerain Solid Self-microemulsion Capsules in Rats in vivo / 中国药房

OBJECTIVE:To study the pharmacokinetic characteristics of Puerarin solid self-microemulsion capsules in rats in vi-vo. METHODS:The rats were randomly divided into two groups with 18 rats in each group. They were given Puerarin solid self-mi-croemulsion capsules(S-SMEDDS capsules)and commercially available Yufeng ningxin tablet,with the dose of 158.15 mg/kg puer-arin. The 0.2 ml blood samples were collected from tail vein 0,5,10,20,40,60,90,120,180,240,360,480,600 min after medication,respectively. The blood concentration of puerarin was determined by HPLC,and pharmacokinetic parameters and rela-tive bioavailability were calculated by using 3p87 software. RESULTS:The metabolism of puerarin was one-compartment model in rats. Pharmacokinetic parameters of S-SMEDDS capsules and Yufeng ningxin tablet were as follows as cmax of (1.032 0 ± 0.020 6) and(0.587 3±0.011 7)μg/ml,t1/2ke of(116.431 4±2.166 0)and(88.222 6±1.752 4)min,AUC0-t of(261.532 2±1.464 0)and (102.835 5±1.957 4)μg·min/ml. Relative bioavailability was 238.77%. CONCLUSIONS:Compared with Yufeng ningxin tablet, S-SMEDDS capsules are absorbed more completely and removed faster.

Preparation and in vitro dissolution evaluation of tanshinone IIA for oral self-microemulsion / 中草药

Objective: To study the prescription and preparation technology of tanshinone IIA for oral self-microemulsifying drug delivery system. The quality, stability, and in vitro dissolution were evaluated. Methods: The prescription and preparation technology were selected and optimized through the solubility experiment, orthogonal design, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter, and stability as selection indexes. The droplet morphous, particle size, drug content, stability, and in vitro dissolution were evaluated after self-microemulsification. Results: The prescription composition of tanshinone IIA self microemulsion was aethylis oleas (50%), polysorbate 80 (40%), and PEG 400 (10%), with oil phase-aqueous phase of 1:50, drug-loaded of 3.0 mg/g, and self-emulsifying time of 1 min. The acquired tanshinone IIA self-microemulsion exhibitted uniform and transparent, with the particle diameter of (51.39 ± 1.50) nm, polydispersity index of 0.211 ± 0.022, Zeta potential of (-11.35 ± 1.19) mV. The results of in vitro dissolution indicated that the accumulative dissolution in 0.1 mol/L HCl solution was able to reach 96% after 30 min. The stability result showed that tanshinone IIA self-microemulsion was affected by high temperature and illumination, indicating having to be stored at 4℃ and protected from light. Conclusion: The preparation of tanshinone IIA self-microemulsion is simple, increasing the solubility in water, making it better absorption in the stomach and intestine, corresponding to the main index of oral drug delivery system and offering the basis for further development and research about tanshinone IIA.

Pharmacokinetics of supersaturable self microemulsion drug delivery system of silybin in rats / 中草药

Objective: To study in vivo pharmacokinetic characteristic of supersaturable self microemulsion drug delivery system (S-SMEDDS) of silybin in rats. Methods: According to the random design, 12 male rats were divided into one control group and one experimental group by six each. SMEDDS of silybin was given to the control group and S-SMEDDS of silybin to the experimental group by both ig administration at dosage of 533 mg/kg, respectively. Blood sampling was conducted by means of an automated blood sampling device (Accusampler) at different time points. After ig administration of S-SMEDDS of silybin to rats, the silybin concentrations in plasma were determined by HPLC and the pharmacokinetic parameters were calculated by non-compartment model of statistical moment analysis. Results: The main pharmacokinetic parameters of the control and experimental groups were as follows: tmax is (1.00 ± 0.40) and (1.50 ± 0.84) h, Cmax is (5.68 ± 0.52) and (16.10 ± 4.06) μg/mL, AUC0→1 is (27.30 ± 3.29) and (82.64 ± 12.36) μg·h·mL-1, respectively. Conclusion: This assessment demonstrates that the oral absorption bioavailability could be substantially improved via the approach: by S-SMEDDS of silybin.

Absorption of curcumin microemulsion in vivo / 中草药

Objective To prepare the curcumin self-microemulsion, observe the morphology and size diameter distribution of the microemulsion, and compare the absorption kinetics of curcumin microemulsion and micelle. To investigate the best absorption segment of curcumin microemulsion in intestnum tenue and the absorption of curcumin self-microemulsion in mouse gastrointestinal tract. MethodsThe intestine in rats was cannulated in situ recirculation. The absorption of curcumin microemulsion was calculated by its decrement in intestnum tenue.The inabsorbable curcumin in all content together with feces in mouse gastrointestinal tract was obtained and used to calculate the absorption rate of curcumin. ResultsThe curcumin microemulsion presented as small spherical drops or something similar under transmission electron microscope (TEM) with the average diameter of about 21.6 nm. The absorption constants of curcumin microemulsion and micelle was 0.042 5 and 0.019 5 /h , the main segments of curcumin microemulsion absorption were intestinum duodenum and intestinum jejunum. The absorption rate of curcumin self-microemulsion was 2.5 times as much as curcumin. ConclusionThe curcumin self-microemulsion could improve the absorption of curcumin in vivo in animal evidently.