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The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Subject(s)
Polysorbates/chemistry , Flavonoids , Pueraria , Surface-Active Agents/chemistry , Ethanol , Emulsions , Particle Size , SolubilityABSTRACT
Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.
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Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.
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Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.
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O BJECTIVE To optimize stir-frying with saltwater technology of Citrus reticulata . METHODS Taking the contents of limonin ，nomilin and obacunone ，color difference value and free radical scavenging rate of 1，1-diphenyl-2-trinitrophenyl hydrazine （DPPH） as the indexes ，the entropy weight method was used for comprehensive evaluation. The stir-frying with saltwater technology of C. reticulata was optimized by central composite design-response surface method by using water-salt ratio ，stewing time，frying temperature and frying time as factors. RESULTS The optimal stir-frying with saltwater technology of C. reticulata included water-salt ratio of 8 ∶ 1（mL/g），stewing time of 22 min，frying time of 9 min and frying temperature of 158 ℃. After three times of validation tests ，the average comprehensive score of the optimized technology was 92.35（RSD＝2.19％），and its relative error with the predicted value （93.25）was 1.10％. CONCLUSIONS The optimal stir-frying with saltwater technology is stable and feasible.
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Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.
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OBJECTIVE：To establish t he metho d for the content determination of pulegone in Schizonepetae tenuifolia decoction pieces and its compound preparation. METHODS ：Hollow fiber liquid-phase microextraction coupled with HPLC （HF-LPME-HPLC） was adopted. Based on single factor tests ，HF-LPME condition of S. tenuifolia decoction pieces and its compound preparation （taking Compound S. tenuifolia granule as an expample ） was optimized by central composite design-response surface methodology using pulegone enrichment multiple as index ，with the concentration of sample phase solution （NaCl），extraction time and stirring speed as factors. Validation test was conducted. HPLC method was adopted to determine the content of pulegone. The determination was performed on Hypersil C 18 column with mobile phase consisted of methanol- 0.3％ phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 252 nm，the column temperature was 25 ℃. The sample size was 20 μL. The feasibility of HF-LPME-HPLC method established in this study was validated by using HPLC method stated in the item of S. tenuifolia decoction pieces in 2020 edition of Chinese Pharmacopoeia （part Ⅰ）as reference. RESULTS ：The optimum HF-LPME conditions included n-nonanol as the extraction solvent ，sample phase solution with 11％ NaCl and pH value of 7，stirring speed of 800 r/min，extraction time of 36 min. Results of HPLC methodology investigation showed that linear range of pulegone were 0.05-5 μg/mL（r＝0.999 0）. The limits of detection and quantitation were 0.4 and 1.3 ng/mL，respectively. RSDs of intra-day and inter-day precision were 1.8％-4.0％ and 1.5％-4.1％（n＝3），respectively. RSDs of reproducibility and stability tests （24 h）were all lower than 8％（n＝6）. Average recoveries of S. tenuifolia decoction pieces and Compound S. tenuifolia granule were 102.6％-105.1％ and 97.2％-102.3％，respectively；RSDs were not higher than 4.1％ and 6.2％（n＝3）. The average contents of pulegone in S. tenuifolia decoction pieces determined by pharmacopoeia method and established method were 0.84 mg/g（RSD＝4.3％ ，n＝3）and 0.87 mg/g（RSD＝5.5％ ，n＝3），respectively，with no significant difference （P＞0.05）. CONCLUSIONS ：The established HF-LPME-HPLC method can enrich and concentrate pulegone ， shows strong purification ability and high sensitivity ，and can be used to determine the contents of pulegone in S. tenuifolia decoction pieces and its compound preparation.
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Objective: To optimize the prescription process of curcumin-piperine polymeric compound micelles (Cur/Pip F127/P123-PM) by central composite design-response surface method. Methods: The content of curcumin and piperine was determined by UPLC. The Cur/Pip F127/P123-PM was prepared by thin film hydration method. Based on the single factor test, the dosage, the mass ratio of F127 and the volume of water were used as independent variables, and the drug loading and entrapment efficiency of curcumin, entrapment efficiency of piperine and the micelle size were dependent variables, and next central composite design-response surface method of three factors and five levels was carried out. The analysis results showed and verified the optimal prescription. Finally, the optimal lyophilization conditions of the micelle preparation were initially screened. Results: The optimal preparation process was as follow: the dosage of curcumin and piperine was 12.96 mg and 0.69 mg, respectively; The mass ratio of F127 was 0.46, and the volume of water was 8.85 mL. The compound curcumin micelles prepared by the optimum formulation had the loading capacity of 5.63%, solubility of 1.27 mg/mL and entrapment rate of curcumin was 86.86%. The entrapment rate of piperine was 77.54%; The micelle size was 66.79 nm and the Zeta potential was close to zero. The lyophilized products prepared by using 8% mannitol as a protective agent had a good redispersion. Conclusion: The model established by central composite design-response surface method can be used to optimize the prescription of compound curcumin micelles, and the method had a high accuracy and good predictability advantage.
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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.
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Objective: Puerarin nanoemulsion (Pue-NE) was prepared with glycyrrhizic acid as a natural stabilizer, and its release characteristics in vitro were investigated. Methods: Data processing was performed using particle size and polydispersity index (PDI) as independent variables, and using the overall desirability (OD) as the evaluation index. The central composite design-response surface method was used to optimize the prescription, and the physical and chemical properties and release characteristics of Pue-NE prepared by the optimal prescription were investigated. Results: The best prescription for Pue-NE is puerarin at a concentration of 5.0 mg/mL, glycyrrhizic acid at a concentration of 1.75 mg/mL, and caprylic glyceride in an amount of 3.5 mL. The average particle size of the nanoemulsion is (184.5 ± 0.8) nm, the PDI is 0.088 ± 0.002, the zeta potential is (10.56 ± 0.35) mv, the conductivity is (98.3 ± 0.4) μs/cm, pH is 6.750 ± 0.005, solubility (4.970 ± 0.008) mg/mL, drug loading is (99.4 ± 0.2)%, turbidity (24.3 ± 1.0) cm-1 (n = 3). It was identified as O/W emulsion by dyeing method. TEM scanning results show that the droplets are spherical and uniform in size and the stability results showed that Pue-NE has good storage stability at 25 ℃. In vitro release results showed that Pue-NE has the greatest release in phosphate buffered pH 6.8 within 24 hours. Conclusion: The preparation of Pue-NE with glycyrrhizic acid as a natural stabilizer is not only simple and convenient, but also can effectively replace the use of traditional chemical synthetic stabilizers and improve the solubility of puerarin.
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Objective: To optimize the formulation of paeonol lipid microspheres (Pae-LM) through central composite design- response surface method and determine its in vitro release characteristics. Methods: Using the mean particle size and centrifugal stability constant (Ke) as evaluation indexes, the oil phase type and the ratio of composite oil, the amount of phospholipid and stearic acid, the type of emulsifier, the type and amount of stabilizer, the quality of PC and CH, the high-speed shear temperature and time, the homogenization pressure and time was screened in prescription process. Effects of dosage of paeonol and high pressure homogenizing pressure on the properties of Pae-LM preparation were investigated by central composite design-response surface method. The binomial model and multivariate linear regression model were used to establish the mathematical relationship between the indexes and the factors. According to the best mathematical model of evaluation index, the response surface was depicted and the best prescription was analyzed by the response surface method. According to the optimized formulation Pae-LM, the in vitro drug release characteristics were investigated. Results: The best prescription of Pae-LM was basically round, with mean particle size of (149.32 ± 0.57) nm, Zeta potential of (-36.01 ± 3.09) mV, encapsulation rate of (98.24 ± 0.32)% and drug-loading rate of (11.94 ± 0.04)%. There was a credible quantitative relationship between Ke and the two factors, and the binomialmodel was more reliable than the multivariate linear model. The cumulative release of paeonol drug substance at 12, 24 and 36 h were 71.84%, 85.21% and 95.07%, while the cumulative release of Pae-LM was only 57.21%, 59.66%, and 63.91% at 12, 24 and 36 h, respectively. The drug release was in accordance with the Ritger-peppas model. Conclusion: Central composite design-response surface method can be applied to optimize prescription of lipid emulsion microspheres. The optimized particle size of Pae-LM was suitable with a higher encapsulation rate, which can provide a reference for the development of paeonol cardiovascular delivery system.
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Objective: To optimize preparation of mitochondrial targeting hyperoside liposomes (DLD/Hyp-Lip), and study its stability in fetal bovine serum, in vitro release behavior and mitochondrial targeting. Methods: DLD/Hyp-lip was prepared by film dispersion method. Single factor experiment was carried out with entrapment efficiency and drug loading as indexes to investigate the effects of the ratio of phospholipids to hyperoside (Hyp) and DSPE-PEG (distearoyl phosphoethanolamine-polyethylene glycol) to DLD on DLD/Hyp-Lip. The formulation of DLD/Hyp-Lip was further optimized by central composite design response surface methodology. The appearance, size and potential of liposomes were observed by transmission electron microscope and particle size analyzer. The stability and drug release rate of liposomes in fetal bovine serum were evaluated by serum stability test and in vitro drug release test. The drug delivery system was evaluated by mitochondrial targeting. Results: The optimal formula of DLD/ Hyp-Lip was as follows: the ratio of total phospholipids to hyperoside was 12.50:1, the ratio of total phospholipids to cholesterol was 6.00:1, and the dosage ratio of DSPE-PEG to DLD was 3:5, the encapsulation efficiency was (95.57 ± 0.56) %, the drug loading was (8.55 ± 0.57) %. The prepared liposomes had good appearance, the particle size of the lip was (124.9 ± 3.4) nm, and the potential was (-6.2 ± 1.9) mV. It was stable in fetal bovine serum and accumulated in vitro release medium for 24 h. Mitochondrial targeting experiments showed that DLD/Hyp-Lip could promote the accumulation of drugs in the mitochondria. Conclusion: This method is simple and convenient, and can accurately and effectively optimize the preparation process of DLD/Hyp-Lip. The prepared DLD/Hyp-Lip has high encapsulation efficiency, small particle size, uniform distribution and good sustained-release effect, which lays the foundation for further in vivo research of DLD/Hyp-Lip. DLD/Hyp-Lip with hyperoside has good mitochondrial targeting of liver cancer cells and is a potentially efficient mitochondrial targeted drug delivery system for liver cancer cells.
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OBJECTIVE：To optimize the formul ation of Polygala japonica cream，and to evaluate the quality of prepared cream. METHODS ：With centrifugal stability ，heat resistance stability and viscosity as evaluation indexes ，the weight coefficient was determined by analytic hierarchy process （AHP），criteria importance through intercriteria correlation （CRITIC）method and mixed weighted AHP-CRITIC ，and the comprehensive score was calculated. The amount of octadecyl alcohol ，hexadecanol and mixed emulsifier （polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82）in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ，particle，pH，stability and rheological characteristics. RESULTS ：The weight coefficients of centrifugal stability ，heat resistance stability and viscosity were 0.428 5， 0.415 6 and 0.155 9 respectively，according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ，5.17 g of octadecyl alcohol ，2.48 g of mixed emulsifier ，1.83 g of polysorbate 60，0.65 g of glyceride monostearate，1 g of benzyl alcohol ，5 g of propylene glycol ，6 g of isopropyl myristate and 5 g of P. japonica extract，and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5；the results of centrifugal test ，heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS ：P. japonica cream is prepared successfully，which shows good apperance ，particle，acidity and stability.
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Objective To avoid the accumulation of copper sulfide (CuS) nanoparticles, prepare and optimize CuS nanoparticles, analyze the factors affecting the particle size and evaluate their photothermal properties. Methods Based on the single factor study, central composite design-response surface methodology was used to optimize the CuS nanoparticle formulation process. The morphology, particle size stability, photothermal conversion efficiency, photothermal stability of optimized CuS nanoparticles were characterized. The toxicity of CuS nanoparticles on 4T1 breast cancer cells and HK2 kidney cells was evaluated by CCK-8 method. In vitro photothermal experiment was used to investigate the ability of CuS nanoparticles on killing 4T1 breast cancer cells. Results The average hydration dynamic diameter of optimized CuS nanoparticles was (10.53±1.63)nm, the actual particle size of CuS nanoparticles showed by TEM image was (3.10±0.81)nm. It had good particle size stability, good photothermal conversion efficiency and photothermal stability. Within the concentration range of 100 μg/ml and 150 μg/ml，it showed no significant toxicity on 4T1 breast cancer cells and HK2 kidney cells, indicating the good stability of CuS nanoparticles. In vitro photothermal therapy showed that CuS nanoparticles had good ability to kill 4T1 breast cancer cells by photothermal. Conclusion The prepared CuS nanoparticles have a small particle size (less than 6nm) and a good photothermal effect, which is expected to solve the problem of CuS nanoparticles accumulation in vivo and make it better for tumor treatment.
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OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.
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OBJECTIVE: To design and evaluate the formula of Weisu microemulsion-ion sensitive gel. METHODS The prescription of microemulsion-ion sensitive gel was conducted on the basis of single factor method and pseudotemary phase diagram method combining with central composite design-response surface methodology. The final formulation was evaluated by particle size, viscosity, potential, contents of naringin, hesperidin and neohesperidin. RESULTS: The optimum prescription ratio of Weisu microemulsion-ion sensitive gel was as following:volatile oil 3 g, RH-40 9 g, PEG-400 3 g, 0.3% deacetylated gellan gum made into 333 mL microemulsion gel. The results of physicochemical properties showed that microemulsion gel appearance was clear. The particle diameter was 20.14 nm. The Zeta potential was -4.04 mV. pH value was 5.43. The contents of naringin, hesperidin and neohesperidin are respectively 6.122 4, 2.094 1, 4.277 mg•mL-1. CONCLUSION: The preparation process of Weisu microemulsion gel is reasonable and feasible. The prepared microemulsion gel is system are stable.
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OBJECTIVE: To prepare simvastatin tablets and optimize its formulation by 3D printing technology. METHODS: A cylindrical tablet with a radius of 4 mm and a thickness of 4.8 mm were prepared by a 3D printer. The dosage of the adjuvant povidone 30(PVP K30), lactose/microcrystalline cellulose (MCC) and absolute ethanol were taken as an investigation factor, the cumulative dissolution rate of 5, 15 and 30 min were used as an evaluation index,and the central composite design-response surface method was used to optimize the formulation and verify, the effect of dissolution were researched by compared with the traditional preparation. RESULTS: The optimal formulation value: the ratio of PVP K30 was 30%, the mass ratio of lactose/MCC was 2.5, the ratio of absolute ethanol was 74%, and the cumulative dissolution in vitro of the printed tablets at 5, 15, 30 min was (45.7±0.5)%, (70.9±0.7)%, (89.7±2.3)% respectively, the deviation between the verification result and the predicted value were less than 5%. The preparation of dissolutioncurve is similar with commercially available formulations. CONCLUSION: The successful preparation of 3D printed simvastatin tablets is simple and the mathematical model is predictive.
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OBJECTIVE: To prepare the ketoprofen microemulsion-based gel in order to expand its drug loading and increase the transdermal permeability. METHODS: The proportion range of oil phase/surfactant in ketoprofen microemulsion were screened by the pseudo-ternary phase diagram. Optimization of formulation for microemulsion gels was conducted by central composite design-response surface methodology with the cumulative permeation quantity across in vitro rat skin and time-lag as evaluation indexes.The transdermal performance of self prepared gel was compared with the commercially available gel. RESULTS: The optimal oil phase, surfactant and cosurfactant of ketoprofen microemulsion were oleic acid, polyoxy ethylene castor oil (EL-35) and ethanol, respectively.The optimal microemulsion formulation was 1.35% oleic acid, 10.8% EL-35, and 9% ethanol by central composite design experiment. The cumulative penetration quantity in 24 h reached 562.82 μg•cm-2 in vitro rat skin was 1.35 times as much as commercially available gel. CONCLUSION: The ketoprofen microemulsion-based gel prepared in this study has good permeability, which lay the foundation for development of the gel.
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Objective To optimize the preparation technology of thermo-reversible Yinhuang opthalimic gel by the central composite design-response surface method.Methods The poloxamer 407 and poloxamer 188 were used as the investigation factors, and the evaluation index was the gel temperature. Central composite design-response surface method was used to evaluate the mathematic relation between the evaluation index and tow investigation indexes to identify the optimum prescription.Results According to the quadratic models, it was found that there was reliable quantitative relation between the evaluation index and two investigation indexes,among which the optimun dosage was 20％ for P407, 1％ for P188, 0.1％ for hyaluronic acid, 0.01％ for benzalkonium chloride, 0.02％ for EDTA.Conclusions This method is reliable and feasible, whicn can realize the prescription optimization of the gel.
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Objective: To prepare nerve growth factor(NGF) temperature sensitive in situ gel and investigate its therapeutic effect on sciatic nerve injury of rats.Method: NGF thermosensitive gel was prepared and its prescription was optimized by central composite design-response surface methodology.Fifty rats were randomly divided into the normal group,model group,NGF injection group(10 mg·L-1),NGF low-dose(10 mg·L-1) and high-dose(20 mg·L-1) thermosensitive gel groups,and sciatic nerve injury model of rats was established.The effect of NGF thermosensitive gel on the injury of sciatic nerve were comprehensively examined by taking rat behavior,sciatic nerve function index(SFI),time of withdrawal reflex,wet weight ratio of gastrocnemius muscle,and histomorphological changes as indicators.Result: The gelation temperature of NGF thermosensitive gel was 35.2℃ after the formulation being optimized,which was in line with the standard for injection.Four-eight weeks after operation,the SFI and wet weight ratio of gastrocnemius muscle in rats of NGF high-dose thermosensitive gel group were significantly higher than those in the model group and NGF injection group,but its time of withdrawal reflex was significantly lower than those in the model group and NGF injection group,and the effect was in a dose-dependent manner.Arrangement of regenerated nerve fibers in sciatic nerve injury area of rats from NGF high-dose thermosensitive gel group was more tidy,dense and continuous than that of the model group.Conclusion: NGF thermosensitive gel can promote repair of sciatic nerve injury in rats.