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@#Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.
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Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.
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Particle Size , Powders , Solvents , TechnologyABSTRACT
Objective: To prepare carboxymethyl Bletilla striata polysaccharide-chitosan@curcumin (CM-BSP) polyelectrolyte complex films, optimize their preparation technology, and evaluate its quality. Methods: CM-BSP was synthesized, then CM-BSP and CS formed water-insoluble complex by electrostatic bonding, the Cur-loaded polyelectrolyte complex films were prepared by a volatilization of solvent method. The formulation and preparation technology were optimized using an orthogonal design method and the morphology and structure were observed by scanning electron microscopy and fourier transform microscopic infrared spectroscopy. Results: The optimal prescription was of CM-BSP 117 mg, CS 233 mg, glycerol 25%, Cur 20 mg. The mean thickness of Cur-loaded polyelectrolyte complex films was (74.0 ± 2.0) μm, drug loading capacities was 95.41%, and in vitro release rate was 93.78%. Conclusion: The obtained polyelectrolyte complex films displayed an smooth exterior inspection, uniform distribution, good drug loading capacities and in vitro release rate.
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Objective: To prepare magnolol solid dispersions (Mag-SD), magnolol phospholipids complex (Mag-PC) and magnolol solid lipid nanoparticles (Mag-SLN), and compare their effects on the pharmacokinetics in vivo. Methods: Solvent evaporation method was used to prepare Mag-SD and Mag-PC. Their existential state of Mag in Mag-SD and Mag-PC were analyzed by X-ray power diffraction (XRPD). High pressure homogenization method was employed to prepare Mag-SLN, its particle size and Zeta potential were also studied. The dissolution in vitro of Mag-SD, Mag-PC and Mag-SLN were also studied compared to magnolol suspension. SD rats in each group were administered intragastrically with magnolol, Mag-SD, Mag-PC and Mag-SLN, respectively. The concentration of magnolol in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. The pharmacokinetic behavior and bioavailability of magnolol, Mag-SD, Mag-PC and Mag-SLN were also compared. Results: The results of XRPD indicated that magnolol showed an amorphous state in Mag-SD and Mag-PC. The average particle size and Zeta potential of Mag-SLN was (161.37 ± 3.77) nm and (-29.16 ± 1.83) mV, respectively. The results of dissolution in vitro indicated that the cumulative dissolution of magnolol was 30.6% within 12 h. Mag-SD, Mag-PC and Mag-SLN enhanced its cumulative dissolution to 96.3%, 76.4% and 45.9%, respectively. The results of pharmacokinetics in vivo showed that Cmax, AUC0-t and AUC0-∞ of Mag-SD, Mag-PC and Mag-SLN were enhanced greatly compared to magnolol suspension. Mag-PC, Mag-SD and Mag-SLN increased its Cmax from (429.67 ± 53.12) ng/mL to (533.62 ± 59.01), (721.73 ± 103.44) and (1 063.21 ± 108.22) ng/mL, respectively. The bioavailability of Mag-SD, Mag-PC and Mag-SLN were enhanced to 1.38, 2.12 and 3.45 times, respectively. Conclusion: Mag-SD, Mag-PC and Mag-SLN could promote the absorption of magnolol in SD rats notably. In addition, Mag-SLN could give a better effect on the bioavailability.
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Objectives To prepare arbutin phospholipid complex (APC) to improve the skin permeability of arbutin and discuss the formation mechanism of APC. Methods Solvent evaporation method was used to prepare APC. The formation of APC was confirmed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy (IR), 1H nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM) and transmission electron microscope (TEM). The solubility, skin permeability and the ability to inhibit tyrosinase of APC were evaluated. Results The analysis showed that the weak interaction between phospholipid and arbutin molecules formed APC. The solubility of arbutin in APC in n-octanol increased from 1.29 µg/mL to 9.54 µg/mL, and the formation of APC effectively increased the lipophilicity of arbutinn. In vitro release study demonstrated that APC exhibited sustained release behavior. Ex vitro penetration studies showed that arbutin was difficult to reach the subcutaneous tissue through the skin, but APC showed strong penetration ability, of which permeation flux was improved from 0.02 mg/cm2 to 0.42 mg/cm2. Enzyme inhibitory activity test showed that the inhibition of APC on tyrosinase activity was 1.85 times of arbutin. Conclusions The formation of the complex improved the bioavailability of arbutin, and the complex held higher application potential for medicinal and cosmetic.
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Efavirenz, a non-nucleotide reverse transcriptase inhibitor is an important drug for treating patients with Human Immunodeficiency Virus infections. It belongs to BCS class II have low solubility and poor intrinsic dissolution rate. It is highly basic (pKa 10.2) which makes it suitable candidate for floating dosage form for continuous delivery in stomach.The study was aimed to improve the solubility by solid dispersion technique.Saturation solubility study and drug content were evaluated for solid dispersion preparation. Saturation solubility shows 8 fold increases in 0.1 N HCL compared to plain drug and drug content was found to be between 95%-102%. Further effervescent floating gastroretentive drug delivery system was prepared by 32 full factorial design with independent variables i.e., concentration of HPMC K100 as matrix forming agent and citric acid as gas generating agent. Lag time, floating time, percent drug release were studied as responses. The optimized batch exhibited floating lag time of 40 sec and the in vitro release studies showed 89.5% drug release in 9 h and tablet remained floating for greater than 8 h. The study thus demonstrated that solubility is increased by solid dispersion technique and floating delivery systems may increase solubility and bioavailability of Efavirenz.
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Objective: To prepare dihydromyricetin (DMY) phospholipids complex (DMY-PC) and its nanostructured lipid carriers (DMY-PC-NLC), and carry out in vitro and in vivo evaluation. Methods: DMY-PC was prepared by solvent evaporation method. High pressure homogenization method was used to prepare DMY-PC-NLC. Orthogonal test was employed to optimize the ratio of solid/liquid lipid, dose of lipids materials, dose of DMY-PC and the concentration of emulsifier of poloxamer. The lyophilized powder of DMY-PC-NLC was prepared with 5% of mannitol as protective agent. The comparation of in vitro release and pharmacokinetics between DMY-PC and DMY-PC-NLC was also studied. Results: DMY was in an amorphous state in DMY-PC. The results of 1HNMR showed that the structure of DMY was not changed. The optimized prescription of DMY-PC-NLC determined by orthogonal test was as follow: The ratio of solid/liquid lipid was 5:1, dose of lipids materials was 325 mg, dose of DMY-PC was 45 mg and the concentration of emulsifier of poloxamer was 0.9%. The average size, Zeta potential, entrapment efficiency and drug loading of DMY- PC-NLC was (197.25 ± 4.42) nm, (-18.2 ± 2.1) mV, (71.68 ± 1.36)% and (3.94 ± 0.24)%, respectively. The in vitro release model was accord with Weibull model and the equation was lnln(1-Mt/M∞)=0.700 1 lnt-1.954 1 (r = 0.971 4). The relative bioavailability of DMY-PC and DMY-PC-NLC were enhanced to 1.63 and 3.22 times compared to DMY, respectively. Conclusion: Compared with DMY-PC, the absorption was promoted by DMY-PC-NLC in further, and the bioavailability of DMY was enhanced effectively.
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AIM To prepare and characterize SiO2 solid dispersions of Curcumae longae Rhizoma extract.METHODS For the solid dispersions prepared by solvent evaporation method,its ratio of extract to carrier (SiO2) was screened by in vitro dissolution test,and the characterization was achieved by determination of particle size,specific surface area,porosity,micromorphology observation,infrared spectroscopy and X-ray.RESULTS When the ratio of extract to carfer was 1:8,three main components (bisdemethoxycurcumin,demethoxycurcumin and curcumin) in the extract reached the highest accumulative dissolution rates.Compared with physical mixture,the solid dispersions demonstrated lower particle size,specific surface area and porosity.Extract was dispensed in the carrier in an amorphous state.CONCLUSION SiO2 solid dispersions can obviously improve the dissolution rates of the main components in Curcumae longae Rhizoma extract.
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Objective Solid dispersion of curcumin and piperine compositions (CUR-PIP SD) was prepared to increase the in vitro dissolution rate and the oral bioavailability of CUR and PIP. Methods The CUR-PIP SD was prepared by a solvent evaporation method with dissolution rate as index. The characterization of CUR-PIP SD was evaluated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and the resulting SD was evaluated by in vitro dissolution assay. UPLC-MS/MS was used to determine the plasma concentrations of CUR and PIP in rats after ig administration. Results In vitro dissolution experiments showed that the dissolution rate of CUR and PIP in SD were both greatly improved compared with that of raw materials. Oral bioavailability of CUR in the SD was 2.71 times of that of the drug substance (P < 0.05), and PIP was increased to 2.68 times (P < 0.05). Conclusion The SD prepared with PVP K30 can effectively increase the in vitro dissolution and bioavailability of CUR and PIP.
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Objective To prepare luteolin solid dispersions (Lut-SD) and luteolin phospholipids complex solid dispersions (Lut-PC-SD), and compare the effects of two kinds of solid dispersions on the bioavailability in vivo. Methods PVP K30 was employed as carrier, and solvent evaporation method was used to prepare Lut-SD and Lut-PC-SD. Their existential state of luteolin in solid dispersions was analyzed by X-ray power diffraction (XRPD). The solubility and dissolution rate were also studied. SD rats in each group were administered intragastrically with Lut, Lut-SD, and Lut-PC-SD, respectively. Their blood samples were collected at different time intervals. Diosmetin was used as internal standard, the concentration of Lut in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. Results The results of XRPD indicated that Lut showed an amorphous state in Lut-SD and Lut-PC-SD. The solubility of Lut was enhanced from (61.09 ± 0.09) μg/mL to (365.33 ± 0.38) μg/mL and (401.14 ± 0.19) μg/mL by Lut-SD and Lut-PC-SD, repectively. The dissolution of Lut was also improved greatly by the two kinds of solid dispersions. Compared to Lut, the bioavailability of Lut-SD and Lut-PC-SD was enhanced to 150.10% and 204.52%, repectively. Conclusion Lut-SD and Lut-PC-SD both could enhance the bioavailability of Lut in SD rats notably. In addition, Lut-PC-SD could give a better effect.
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AIM To prepare the matrine nanoparticles and their wheat germ agglutinin-modified product.METHODS Double emulsification-solvent evaporation method was employed to prepare matrine nanoparticles.In consideration of influencing factors of ratio of poly (lactic-co-glycolic acid) to matrine,rotational speed and polyvinyl alcohol concentration,as well as the evaluation indices of particle size,potential,encapsulation efficiency and drug load,the preparation was optimized by central composite design.Wheat germ agglutinin-modified matrine nanoparticles were prepared by carbodiimide method.In addition to the influencing factors of ratio of carbodiimide to N-hydroxysuccinimide,wheat germ agglutinin addition and incubation time,evaluation indices of particle size,potential and modification rate were also taken into account in the preparation optimization by uniform design.RESULTS The optimal conditions for matrine nanoparticles were determined to be 0.594 ∶ 1 for ratio of poly (lactic-co-glycolic acid) to matrine,815 r/min for rotational speed,and 0.46％ for polyvinyl alcohol concentration.The average particle size,potential,encapsulation efficiency and drug loading were 112.04 nm,-15.38 mV,90.05％ and 27.14％,respectively.The optimal conditions for their wheat germ agglutinin-modified product were found to be 2.8 ∶ 0.12 for ratio of carbodiimide to N-hydroxysuccinimide,3 mg for wheat germ agglutinin consumption,and 14 h for incubation time.The average particle size,potential and modification rate were 474.7 nm,-5.2 mV and 69.51％,respectively.CONCLUSION The preparation techniques are reliable,and the matrine nanoparticles and their wheat germ agglutinin-modified product show their stable properties.
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ABSTRACT Acyclovir is an antiviral drug having potent activity against the virus of herpes family and varicella zoster. Unfortunately, drug suffers very poor oral bioavailability (15-30%). The main objective of present study was to develop acyclovir cocrystals with improved solubility which may result in improvement of bioavailability. Hansen solubility approach was used as a tool to predict the cocrystal formation of a drug with selected coformer. Cocrystals of acyclovir with various coformers were screened in order to enhance their water solubility. Cocrystals of the drug were prepared using various methods like solvent evaporation, wet grinding, and antisolvent addition. Formation of cocrystals by solvent evaporation method was found to be better method amongst all. Optimization of cocrystal formation was carried out by employing different solvents as well as the stoichiometric ratio of acyclovir with that of coformer. Synthesis of cocrystals was optimized using water as a solvent system resulted in good agreements. The potential cocrystal formation of acyclovir was characterized by IR, PXRD and DSC techniques. An in-vitro dissolution study was performed to determine the dissolution rate of cocrystals. The results suggest that acyclovir forms cocrystals with tartaric acid and the initial dissolution rate of synthesized cocrystals were considerably faster as compared to pure acyclovir.
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Solubility , Acyclovir/analysis , Reference Standards/classification , Solvents/therapeutic use , DissolutionABSTRACT
<p><b>OBJECTIVE</b>To study the biocompatibility of the polylactic acid (PLA)-absorbable root post film prepared by solvent evaporation film.</p><p><b>METHODS</b>The PLA post film-leaching liquor was prepared by the solvent evaporation of PLA root post films, and its biocompatibility was measured. Sources of human gingival fibroblasts (HGF) were cultivated in vitro and identified initially by the immunohistochemistry method. The toxicity reaction, survival rate, and morphological change of HGF incubated in PLA post film-leaching liquor were observed and tested by morphological observation, 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry. The HGF were implanted on the PLA post film and observed by 4',6-diamidino-2-phenylindole staining. After implanting the PLA post film, the surrounding subcutaneous tissue of SD rats and the implants were removed from the back of the rats in the 1st, 4th, 8th, and 12th weeks to observe the general condition of the incisions. The organization was given the hematoxylin-eosin (HE) stain to find the organization condition of local tissue inflammation and foreign body reaction through the infiltration degree of inflammatory fibroblasts.</p><p><b>RESULTS</b>The effects of the PLA post film-leaching liquor on the proliferation of HGF and fibroblast toxicity were insignificant. The living fibroblast rate was similar to the normal control group. The HGF were able to grow on the PLA film. The results of the organization general observation and HE staining of the rats were similar to the results for the control group, which met all the demands made by biological safety.</p><p><b>CONCLUSIONS</b>The PLA-absorbable root post film prepared by the solvent evaporation film has good biocompatibility and can be used for further clinical research.</p>
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Animals , Rats , Biocompatible Materials , Fibroblasts , Polyesters , Rats, Sprague-Dawley , Tooth RootABSTRACT
OBJECTIVE: To prepare capsaicin-solid lipid nanoparticles (CAP-SLNs) and study their physical and chemical properties. Then, the CAP-SLNs were modified with chitosan (CTS) and the pharmacokinetics across colon of rats was studied in vivo. METHODS: CAP-SLNs were prepared by emulsion-solvent evaporation method. The mean size, encapsulation efficiency and drug loading of the nanoparticles were investigated. RESULTS: The average diameter of CAP-SLNs was (118.89 ±25.0) nm, the encapsulation efficiency was (38.56 ±2.6)%, and the drug-loading was (6.17 ±0.21)%. After colon-specific delivery in rats, the AUC0.360 min(243. 63 ±61.46) mg · min · L-1 and ρmax(1.23 ±0.18) mg · L-1 of CTS-CAP-SLNs were 1.81-fold and 1.95-fold higher than CAP. CONCLUSION: It is simple and feasible to prepare CAP-SLNs by emulsion-solvent evaporation method. The pharmacokinetic parameters in rats are improved remarkably compared with CAP.
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Objective: To prepare cucurbitacin B phospholipids complex (CuB-PLC) and evaluate its physicochemical properties and in vitro antitumor activity. Methods: CuB-PLC was prepared using solvent evaporation method and optimized by Box-Behnken design. The oil-water partition coefficient, particle size, and morphology of CuB-PLC were investigated; X-ray diffraction (XRD) spectroscopy and infrared (IR) spectroscopy were used to analyze the formation machenism of CuB-PLC. MTT method was used to determine the in vitro antitumor activity of CuB-PLC. Results: The optimal formulation protocol for CuB-PLC was as follows: Tetrahydrofuran was taken as the reaction medium, phospholipids-cucurbitacin B molar ratio, reaction concentration of cucurbitacin B, reaction temperature and time were 1:1, 1.5 mg/mL, 60℃, and 3 h, respectively. The complex rate and particle size for the optimized CuB-PLC was 97.15% and (521.30 ± 10.50) nm, and the polydispersity index (PDI) was 0.133 2 ± 0.024 0. MTT experiments showed that the half of the HepG-2 cell proliferation inhibition concentration (IC50) values of CuB and CuB-PLC were 42.55 and 27.61 μmol/L. Conclusion: CuB-PLC is successfully developed under the optimized protocol, possessing high complex rate, and enhanced solubility in water, and the inhibition on HepG-2 cell proliferation is significantly enhanced, which provides the reference for the further research of CuB.
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Objective: To prepare scutellarin-piperine co-amorphous complex, in order to improve their dissolution and solubility. Methods: Scutellarin-piperine co-amorphous complex was prepared using solvent evaporation method. The microscopic structure and physicochemical properties of co-amorphous complex were analyzed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and infrared vibrational spectra (IR). And its in vitro release also was investigated. The formation of the co-amorphous complex in scutellarin and piperine was studied. Results: DSC and XRD analysis suggested that scutellarin and piperine may be present as amorphous substance. IR results indicated molecular interactions between scutellarin and piperine. The in vitro release determination results of scutellarin-piperine co-amorphous complex showed accumulated dissolution rate of scutellarin and piperine could both be improved. Conclusion: The drug-drug co-amorphous system can provide certain reference for insoluble drugs to improve their dissolution and solubility.
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OBJECTIVE: To prepare lappaconitine (LA)-loaded polylactic acid (PLA) nanoparticles (LA/PLA NPs) and investigate its release properties in vitro. METHODS: LA/PLA NPs were prepared by optimized emulsion-solvent evaporation method with biodegradable PLA as carrier material and polyvinyl alcohol (PVA) as emulsifier. The entrapment efficiency and drug loading rate of LA were used as the main evaluation indexes to optimize the preparation process by orthogonal design method. The mean particle size was measured by laser particle size analyzer; the morphology of LA/PLA NPs was observed by atomic force microscope; the in vitro release behavior was studied by dynamic dialysis. RESULTS: The optimized LA/PLA NPs were spherical. The mean particle size was (429±9.19) nm, the entrapment efficiency and drug loading rate were (86.34±2.15)% and (45.85±1.34)%, respectively. The in vitro release study showed that the LA/PLA NPs could provide a continuous release of LA for 15 d. CONCLUSION: LA/PLA NPs with high entrapment efficiency and drug loading rate are prepared successfully, and show sustained release effect for LA in vitro.
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OBJECTIVE:To prepare and characterize celecoxib-loaded PLGA nanoparticles. METHODS:Emulsification-solvent evaporation method was adopted to prepare celecoxib-loaded PLGA nanoparticles. With encapsulation efficiency and particle size as the indexes,Plackett-Burman design was preferred to screen the formulation and variables which had a significant effect on the property of nanoparticles. And then Box-Behnken response surface method was used to further optimize selected variables including mass concentration of PLGA,ultrasonic power and ultrasonic time,followed by verification. Malvern particle size analyzer was used to determine the particle size distribution of nanoparticles and Zeta potential of nanoparticle by the optimal formulation technol-ogy,and transmission electron microscope was used to observe the morphology of the nanoparticles,and their drug release in vitro behavior and stability(25,5 ℃)were also observed. RESULTS:The optimal formulation and technology was as follows as PLGA mass concentration of 30.0%,ultrasonic power of 180 W and ultrasonic time of 8 min. For the prepared nanoparticles,encapsula-tion efficiency and particle size were (85.7 ± 4.1)% and (226.1 ± 36.1) nm (n=3) respectively;particle size distribution was (176.2±41.2)nm,polydispersity index was 0.211±0.021,and Zeta potential was(-37.3±1.6)mV. Under the electron micro-scope,the nanoparticles were homogeneous in particle size and distributed spheroidally,with 24 h accumulative release of 52.4%. They were stable within 3 months at 5℃. CONCLUSIONS:Celecoxib-loaded PLGA nanoparticles have been prepared successfully.
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Solid dispersion is one of the most widely used methods to enhance the solubility and dissolution rate of poor water soluble drugs. In the present study, flurbiprofen solid dispersions were prepared using solvent evaporation method by incorporating polyethylene glycol 20000 and evaluated for solubility studies, drug-carrier compatibility studies and in vitro dissolution studies. From the solubility studies, formulations F4 were selected to prepare in the form of tablets and compared with control tablets (conventional tablets using pure drug). From the results of in vitro dissolution study, tablets containing polyethylene glycol 20000 showed almost complete drug release within the 15 min. The percent drug release in 15 min (Q15) and initial dissolution rate for formulation F4 was 99.26±1.12%, 6.62%/min. These were very much higher compared to control tablets (34.95±1.29%, 2.33%/min). The relative dissolution rate was found to be 2.84 and dissolution efficiency was found to be 57.48 and it is increased by 3.5 fold with F4 formulation compared to control tablets (17.91). From the above results, it is concluded that the formulation of solid dispersions using polyethylene glycol 20000 is a suitable approach to improve the solubility and dissolution rate of flurbiprofen.
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OBJECTIVE: To prepare PLGA-PLL-PEG nanoparticles simultaneously loaded with daunorubicin (DNR) and tetrandrine (Tet).