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OBJE CTIVE To prepare and characterize evodiamine phospholipid complex self-microemulsifying drug delivery system（EVO-PC-SMEDDS），and to investigate its gastric mucosal permeability. METHODS EVO-PC-SMEDDS was prepared ， and particle size ，polydispersity（PDI）and Zeta potential were tested ，and microscopic observation was carried out. The stability of EVO-PC-SMEDDS in simulated gastric liquid with different pH （1.2，2.0，4.0，7.0）was investigated. The entrapment efficiency and drug-loading amount of the preparation were determined ，and the in vitro release was investigated. The gastric mucosal permeability of EVO-PC-SMEDDS was studied by combining rat gastric mucosal tissue and Ussing Chamber technology. RESULTS The particle size of EVO-PC-SMEDDS was （53.63±1.51）nm，PDI and Zeta potential were 0.217±0.017 and （－12.20±0.15）mV，entrapment efficiency was （95.25±0.97）％ and drug-loading amount was （19.30±1.21）mg/g. EVO-PC- SMEDDS exhibited a uniformly dispersed round spherical shape under transmission electron microscope. Stability experiments showed that EVO-PC-SMEDDS exhibited no significant change in particle size ，PDI and Zeta potential under the simulated gastric fluid with different pH and showed excellent stability. Results of in vitro release test showed that compared with evodiamine （EVO），in vitro accumulative release of EVO-PC-SMEDDS were enhanced 6.83-fold，which was in line with the first-order kinetic release model. Results of gastric mucosal permeability showed that gastric mucosal permeation transport ，permeation rate ， permeation flux and area under curve of cumulative permeability of EVO-PC-SMEDDS were higher than those of EVO ， respectively. CONCLUSIONS EVO-PC-SMEDDS is prepared N successfully and shows good stability. It could significantly improve the release behavior and gastric mucosal permeability of EVO.
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OBJECTIVE：To study the anti-tumor effect of artemether （ARM）self-microemulsifying drug delivery system （SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS ：Human glioma cell line SHG 44 was inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th day after inoculation ，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model ，and then divided into control group （normal saline ），ARM suspension group [ 60 mg/（kg·d）]，ARM-SMEDDS low-dose ，medium-dose and high-dose groups [ 10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and relevant solution intragastrically once a day ，for consecutive 30 d. The weight change and general sibuation of mice were recorded. The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS ：The subcutaneously transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general situation was normal ，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group （P＜0.05）. At 15th day of administration ，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension group（P＜0.05）. After last administration ，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS ：ARM-SMEDDS show significant inhibitory effect on the proliferation of human glioma ，and are better than suspension with higher dosage.
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Objective: To study the prescription and preparation technology of licorice flavonoids self-microemulsifying drug delivery system (LF-SMEDDS) and evaluate its quality. Methods: The optimal formulation of LF-SMEDDS was screened by test of solubility, compatibility of oil and emulsifier, and pseudo-ternary phase diagram. Simplex lattice method was applied to optimize formulation with average particle size, polydispersity index and drug loading as evaluation indexes, the physicochemical characteristics, in vitro dissolution and stability were also determined. Results: The optimal prescription composition of LF-SMEDDS was 10% of Cinnamomi Cortex oil, 55% of RH-40, and 35% of 1,2-propanediol. The LF-SMEDDS exhibited uniform and transparent appearance, with the average particle size of (16.30 ± 0.22) nm, polydispersity index of 0.155 ± 0.008, Zeta pontential of (-20.11 ± 0.50) mV and drug loading of (86.03 ± 0.37) mg/g. The results of in vitro dissolution test indicated that the accumulative dissolution of LF was 90.65% at 30 min. The stability experiment showed that LF-SMEDDS was affected by high temperature and illumination, indicating that it should be stored at low temperature and protected from light. Conclusion: The LF-SMEDDS is simple in preparation and stable in quality, significantly increasing the solubility of LF and improving its oral bioavailability, which can provide reference for further research and development about the related preparations of the active fraction.
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Olmesartan medoxomil (OLM) is a novel selective angiotensin II receptor blocker USFDA approved drug for the treatment of hypertension. The oral bioavailability of OLM is 26% in healthy humans due to low solubility in water. The aim of the present investigation was to develop a self–microemulsifying drug delivery system (SMEDDS) to enhance the solubility of OLM. The screening study of OLM with different oils, surfactants and co–surfactants was done. Out of study optimized batch was converted in to solid freeze dried powder using 2% w/v mannitol as cryoprotcatant by lyophilization technique. This freeze dried powder shown good flow properties. The in vitro dissolution shown that about 99.28±0.013%of the drug is released within 45 min in freeze dried Solid–SMEDDS, while plain drug showed only 37.88±0.025% and marketed tablet shown only 58.31±0.015 % dissolution at the end of 45 min. The in vitro dissolution studies indicate that formulation of OLM in the form of freeze dried powder enhances the dissolution properties.
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The mesoporous silica nanoparticles (MSN) in different pore size and sirolimus (SRL) loaded self-microemulsifying drug delivery system (SMEDDS) were prepared. The results in morphology were collected by scanning electron microscope, transmission electron microscope, small-angle X-ray diffraction, and N2 adsorption-desorption. The results showed that the prepared MSN has ordered nanochannels with a pore size of 6.3, 8.1, 10.8 nm, respectively. The particle size of SRL-SMEDDS were measured by particle sizing system, which was 20.6±1.3 nm. The stirring method was developed to prepare SRL-SMEDDS-MSN. It was found that the optimal ratio of SRL-SMEDDS to MSN was 2:1, while the drug loading rate was near 0.83%, and the flow properties of SRL-SMEDDS-MSN were of good condition. The differential scanning calorimetry results proving a molecular or amorphous dispersed state of SRL in MSN while the suspension experiment has shown great reconstitution properties of SRL-SMEDDS-MSN. There is no significant influence on maximum drug release rate of different pore size of SRL-SMEDDS-MSN in 250 mL water within 2 h, while the results of the first 40 min have an obvious difference. Above all, MSN might provide a new strategy for the solidification of SMEDDS.
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Objective:To prepare the self-microemulsifying drug delivery system (SMEDDS) and relevant tablets of atorvastatin calcium and ezetimibe(Ato-Eze),and investigate the in vitro release of Ato-Eze SMEDDS tablets. Methods:The solubility and excip-ient compatibility of Ato and Eze in different excipients were investigated. The pseudo-ternary phase diagram composed of different oil phase,emulsifier and co-emulsifier was used to obtain the self-emulsifying area. The morphology,particle size distribution and zeta po-tential of microemulsion were determined by a dilution method. The optimal formula of Ato-Eze SMEDDS was prepared into tablets. The drug release profiles of the commercial formula,Ato-Eze SMEDDS and Ato-Eze SMEDDS tablets were compared. Results:The op-timal formula was as follows:propylene glycol monocaprylate as the oil phase,Solutol HS 15 as the surfactant and polyethylene glycol 600 as the co-surfactant with the best ratio of 5 :3.75:1.25. Ato-Eze SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope. The particle size and zeta potential of Ato-Eze SMEDDS was(44.2 ± 19.5) nm and( -24.1 ± 1.3) mV,respectively. The in vitro release profile indicated that the accumulated re-lease of Ato-Eze SNEDDS and the tablets reached up to nearly 100% in 45 min. Conclusion: Ato-Eze SMEDDS tablets can signifi-cantly improve the in vitro dissolution rates of the two drugs,and the preparation process is simple and feasible.
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Objective: To develop and optimize a self-microemulsifying drug delivery system (SMEDDS) formula for improving the dissolution of atorvastatin calcium.Methods: Solubility and pseudo-ternary phase diagram were used to select the suitable type and amount range of oil phase, surfactant and co-surfactant.D-optimal mixture design was used to optimize the formula of atorvastatin calcium SMEDDS.The morphology, particle size distribution and zeta potential of the microemulsion were determined by a dilution method.The in vitro drug release profiles of the marketed atorvastatin calcium tablets and the self-made SMEDDS were compared.Results: The formula of atorvastatin calcium SMEDDS was as follows: Capmul MCM as the oil phase, Labrasol as the surfactant and Transcutol P as the co-surfactant with the optimal weight ratio of 13.0∶43.5∶43.5.The self-made SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope.The particle size, PdI and zeta potential of the self-made SMEDDS was (34.2±13.6) nm, (0.169±0.04) and (-21.1±1.3) mV, respectively.The in vitro release profile indicated that the accumulated release of the self-made SNEDDS reached up to nearly 100% in 45 min.Conclusion: The optimal formula of atorvastatin calcium SMEDDS optimized by D-optimal mixture design can improve the drug dissolution rate effectively.
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Objective: To prepare the total saponins from Paris Polyphylla self-microemulsifying drug delivery system (SMEDDSs) and its solid fied granule, and investigate the in vitro release.Methods: The solubility of the total saponins from Paris Polyphylla in different excipients was investigated.The pseudo-ternary phase diagram composed of different oil phase, emulsifier and co-emulsifier was used to define the self-emulsifying area.The optimal formula of the total saponins from Paris Polyphylla SMEDDSs was prepared into granule.The appearance, morphology, particle size distribution, PdI and zeta potential of the microemulsion and the granule were determined by a dilution method.The drug release profile of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule were compared.Results: The optimal formula of SMEDDSs was as follows: propylene glycol monocaprylate as the oil phase, Tween-80 as the emulsifier and propylene glycol as the co-emulsifier with the optimum ratio of 7.0∶1.5∶1.5.After diluted by water,the total saponins from Paris PolyphyllaSMEDDSs and the granule formed a clear and transparent microemulsion solution with small homogeneous spheres as seen under a transmission electron microscope.The average particle size of the total saponins from Paris Polyphylla SMEDDSs and the granule was (58.6±16.4) nm and (68.1±12.1) nm with PdI of (0.183±0.04) and (0.209±0.05), respectively, and the zeta potential was (-20.2±1.9) mV and (-18.9±1.5) mV, respectively.The results of transmission electron microscopy showed the microemulsion was round, regular and spherical distribution.The in vitro release profile indicated that the accumulated release of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule was more than 85% in 45 min.Conclusion: The self-microemulsifying granule can significantly improve the in vitro dissolution rate of the total saponins from Paris Polyphylla, and the preparation process is simple and feasible.
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Objective To investigate celecoxib self-microemulsifying drug delivery system (CXB-SMEDDS) that was developed to increase the dissolution rate and oral bioavailability of celecoxib.Methods The formulation of CXB-SMEDDS was optimized by pseudo-ternary phase diagrams analysis.The appearance, morphology, particle size distribution and in vitro drug release behavior of CXB-SMEDDS were investigated after diluted by water.The bioavailability of CXB-SMEDDS was determined by oral administration to rats compared with CXB suspension.Results An optimized formulation was selected: Medium chain triglycerides as oil phase, Tween 20 as surfactant, Transcutol HP as cosurfactant.The ratio of oil phase, surfactant and cosurfactant was 2∶9∶9.Upon mixing with water, CXB-SMEDDS formed a clear and transparent microemulsion solution with homogeneous small spherical under transmission electron microscopy.For particle size of CXB-SMEDDS was found to be (57.6±14.2) nm.The in vitro dissolution test indicated a significant improvement in release characteristics of CXB.The AUC of CXB-SMEDDS and CXB suspension were (5.54±0.94) and (3.32±0.59) mg·L-1·h, respectively.The relative bioavailability was 166.9%.Conclusion The SMEDDS can significantly increase celecoxib dissolution in vitro and bioavailability in vivo.
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Objective:To study the formula of triptolide (TRI) self-microemulsifying drug delivery system (SMEDDS) and evaluate the pharmaceutical properties.Methods:The formula and preparation process of triptolide self-microemulsion were screened by the solubility test and pseudo-ternary phase diagram.With the average particle size and self-microemulsifying time as the indices,the further formula optimization of triptolide self-microemulsion was carried out.The pharmaceutical properties of triptolide self-microemulsion were evaluated.Results:The optimal formula of TRI SMEDDS was as follows:the amount of medium chain triglycerides (MCT) was 20%,that of polyoxyethylene castor oil (EL-35) was 40%,and that of polyethylene glycol 400 (PEG-400) was 40% in the oil phase.The average particle size was 43.48 nm,and the time of self-microemulsification was less than 30 s.Conclusion:The average particle size and the appearance of triptolide self-microemulsion are accordance with the requirements of pharmaceutics.Triptolide self-microemulsion has good sustained-release effect,which lays foundation for the further study on pharmacodynamics.
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Objective:To establish an HPLC method to determine the entrapment efficiency (EE) and drug loading (DL) of curcumin (CUR)and quercetin (QUE)loaded self-microemulsifying drug delivery system.Methods:A centrifugation method was used to isolate the free drug.The content of drug was determined by HPLC.The analytical column was a Purospher STAR LP C18 column (250 mm×4.6 mm,5 μm) and the column temperature was 30 ℃.The mobile phase was acetonitrile-4% acetic acid (50∶50) and the flow rate was 1.0 ml·min-1.The UV detection wavelength was set at 370 nm and the injection volume was 10 μl.Results:CUR and QUE were linear within the range of 10.728-96.552 μg·ml-1 (r=0.999 8) and 1.08-9.72 μg·ml-1 (r=0.999 9),respectively.The average recovery was 99.98%(RSD=1.46%,n=9) and 100.34%(RSD=1.06%,n=9),respectively.In CUR-QUE-SMEDDS,the EE of curcumin and quercetin was (95.97±0.50)% and (95.91±2.52)%,and the DL was (25.82±0.15) mg·g-1 and (1.80±0.05)mg·g-1,respectively.Conclusion:The method is accurate,rapid and simple,and suitable for the determination of DL and EE in CUR-QUE-SMEDDS.
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Objective To screen the formulation of self-microemulsifying drug delivery system (SMEDDS) for sirolimus (SRL) and prepare the SRL-SMEDDS pellets.Methods Co-emulsifier,oil phase and emulsifier were chosen by solubility test and ternary phase diagrams,central composite design and response surface method were adopted to screen and optimize the preparation and formulation of liquid SRL-SMEDDS.The selected liquid SRL-SMEDDS formulations were prepared into pellets by extrusion-spheronization method.Results The final pellets from liquid SRL-SMEDDS formulation :SRL 0.4%,Labrafil M1944CS 9.3%,Cremophor EL 15.9%,Transcutol P 8.0%,MCC 49.8%,lactose 13.3%,CMS-Na 3.3%.Dissolution test showed superphosphate (SSP) in the dissolution water is much greater than the commercially available sirolimus tablets ;while in 0.4% SDS solution,the two formulations showed similar dissolution.Conclusion SMEDDS can improve the dissolution of SRL in v itro.
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Objective:To optimize the formula composition of rutin self-microemulsifying drug delivery system by pseudo-ternary phase diagram.Methods:The oil, surfactant and co-surfactant were chosen by the solubility test , and the formula of rutin self-microe-mulsifying drug delivery system was optimized by pseudo-ternary phase diagram .Results: The formula of rutin self-microemulsifying drug delivery system was with the mass ratio of oleic acid , Cremopher RH40 and absolute ethyl alcohol of 23∶36∶12 .The microemul-sion was clear transparent liquid .Conclusion:The prepared rutin self-microemulsifying drug delivery system using the optimized for-mula screened by pseudo-ternary phase diagram can increase the solubility of rutin significantly .
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Objective: To improve the absorption of trifolirhizin (Tri) isolated from Sophora flavescens through preparing it to be phospholipid complex self-microemulsion. Methods: In this study, we used the silica gel column chromatography and recrystallization technology to separate and prepare trifolirhizin; And we used physical and chemical properties and spectral data to identificate the structure. We used the orthogonal experiment and the central composite design response surface method (CCD-RSM) to optimize the Tri phospholipid complex (TPC), Tri phospholipid composite material self micro-emulsifying drug delivery system (TPC-SMEDDS), and used the Caco-2 model to investigate the transmembrane transport of Tri, TPC, and TPC-SMEDDS, respectively. Results: The concentration of the phospholipid complex was 4 mg/mL, the ratio of drug to lecithin was 1:1.5, the reaction time was 3 h, the composite rate was (93.20±2.01)%. The emulsifier was polyoxyethylene castor oil (Cremphor EL40), the auxiliary emulsifier was diethylene glycol ethyl ether (Transcutol HP), and the weight ratio (Km) of phospholipid complex was 7.58. The experiments of Caco-2 cell showed that the Papp of Tri was 2.45×10-7 cm/s; The Papp values of TPC and TPC-SMEDDS were 5.13×10-6 and 1.847×10-5 cm/s, respectively. Conclusion: The permeability coefficient of Tri can be obviously improved by using phospholipid complex and self-microemulsion technique, which also can improve the efficiency of drug delivery.
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Objective: Optimization of ginkgolides components (GC) self-microemulsifying drug delivery system (SMDDS) (GC-SMDDS) and similarity analysis on each drug release. Methods: Using equilibrium solubility to screen the oil phase, emulsifier, and co-emulsifier; Taking appearance, the proportion of microemulsion particle size, Zeta potential, surfactants and co-surfactants, and surfactant mixing ratio of the oil phase as study factors, pseudo-ternary phase diagrams were used to screen GC-SMDDS process. SMEDDS of drug loading, particle size distribution, Zeta potential, and stability were evaluated. With the aid of the similarity factor and the curve linear regression slope analysis, the similarity between the composition of the component and the rate and extent of drug release was analyzed. Results: Optimal prescription of polyoxyethylene and polyethylene glycol 200 mass ratio of 4:1, ethoxylates and polyethylene glycol quality and bitterness total mass of 200 capric triglycerides ratio of 9:1, drug content of 100 mg/g. Particle size under 40 nm, ginkgolides 48 h internal components from microemulsion to room temperature, high temperature, and low temperature stability is good. The release quantity achieves the synchronous drug release with the similarity of 96.9%. Conclusion: The SMDDS not only can improve the dissolution of difficult soluble drugs, but also independently regulate the drug release behavior of each component so as to make the drug release maintain good consistency.
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The aim of the study was to prepare and evaluate the quality of negatively charged selfmicroemulsifying drug delivery system of curcumin (NC-CUR-SMEDDS).Based on the CUR-SMEDDS,the optimum amount of excipients was confirmed by the single-factor design experiment taking mean particle size,Zeta potential,drug entrapment efficiency and the drug loadings of curcumin as the evaluation indices for the preparation of NC-CUR-SMEDDS.The quality of NC-CUR-SMEDDS was evaluated by observing its appearance status,transmission electron microscope micrographs and determining particle diameter,Zeta electric potential,drug entrapment efficiency and drug loading.As a result,it was found that the Zeta potential reached -43.43 ± 0.29 mV when 4％ docusate sodium was added.The appearance of NC-CUR-SMEDDS remained clarified and transparent,and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution.The mean particle size was 14.08 ± 0.082 nm,the drug loading of curcumin was 26.48 mg·g-t and the drug entrapment efficiency was 94.12％.It was concluded that NC-CUR-SMEDDS with high entrapment efficiency and uniform particle size distribution met the requirement of inflammatory target binding in the colon.
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OBJECTIVE:To study relative bioavailability of dauricine self-microemulsifying drug delivery system (SMEDDS) in rats. METHODS:12 rats were randomly divided into dauricine SMEDDS group (20 mg/kg) and dauricine solution group (50 mg/kg),6 rats in each group. They were given relevant medicine intragastrically. Then,0.3 ml plasma was collected from orbital venous plexus before medication and 0.167,0.333,0.5,0.75,1,2,4,8,12,24,36 h after medication. The plasma concentration of da- uricine was determined by HPLC-MS/MS,and DAS 3.0 was used to calculate pharmacokinetic parameters and evaluate the relative bioavailability of dauricine with dauricine SMEDDS. RESULTS:The linear range of dauricine in plasma were 2.12-424 ng/ml (r=0.999 9);RSDs of intra-day and inter-day were all lower than 10%. Pharmacokinetic parameters of dauricine solution and dau-ricine SMEDDS were that cmax were(126.3±37.4)ng/ml and(179.6±51.5)ng/ml;t1/2 were(11.48±4.58)and(21.79±6.59)h;AUC0-t were (1 963.5±638.3)ng·h/ml and(2 535.8±739.5)ng·h/ml;AUC0-∞ were(2 256.3±703.5)ng·h/ml and(2 854.6± 768.7)ng·h/ml,respectively. The relative bioavailability of dauricine SMEDDS were 323% and 316% by calculating with AUC0-t and AUC0-∞,respectively. CONCLUSIONS:Intragastric administration of dauricine SMEDDS can improve relative bioavailability of dauricine significantly.
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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.
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The present investigation is aimed to develop self-microemulsifying drug delivery system (SMEDDS) to improve the in vitro dissolution of a BCS (Biopharmaceutical Classification System) class II anti emetic agent, domperidone. Solubility study was performed to identify the ingredients showing highest solubility of domperidone. The ternary phase diagrams were plotted for selected components to identify the area of microemulsion existence. D-optimal mixture experimental design was applied to optimize a liquid SMEDDS using formulation variables; the oil phase X1 (Oleic acid), the surfactant X2 (Labrasol) and the co-surfactant X3 (Transcutol HP). The liquid SMEDDS were evaluated for droplet size, emulsification time, % transmittance and drug release. Stability study was performed at 40 °C/75% RH. Liquid formulation was solidified by adsorption on carrier Aerosil 300. Solid SMEDDS was evaluated and compared with liquid SMEDDS and marketed formulation. Oleic acid was selected as oil, Labrasol as surfactant and Transcutol HP as co-surfactant for formulation of SMEDDS. The optimized batch showed best results in terms of smaller droplet size (<170 nm), emulsification time (<40 s) and drug release (>85% in 15 min) and was stable for 3 months. Solid SMEDDS containing Aerosil 300 showed good flow properties and uniform drug content. XRPD study revealed that the crystalline drug was converted to amorphous form in solid SMEDDS. The rate and extent of drug dissolution from solid SMEDDS was significantly higher than pure drug and commercial tablet formulation. The results demonstrate the potential of SMEDDS as a means of improving solubility, dissolution and hence the bioavailability.
O presente estudo teve como objetivo desenvolver sistemas de liberação auto-microemulsificantes (Self-Microemulsifying Drug Delivery System - SMEDDS) de domperidona, agente antiemético, classe II, segundo o sistema de classificação Biofarmacêutica, para melhorar sua dissolução in vitro. Estudo foi realizado para identificar os componentes que revelaram maior solubilidade da domperidona. Determinaram-se os diagramas de fase ternários para esses componentes selecionados tendo em vista a identificação da região de formação da microemulsão. O planejamento experimental foi empregado para otimizar os SMEDDS líquidos, utilizando as seguintes variáveis de formulação: a fase oleosa X1 (ácido oleico), o agente tensoativo X2 (Labrasol) e co-tensoativo X3 (Transcutol HP). Os SMEDDS líquidos foram avaliados quanto às seguintes características: tamanho da gota, tempo de emulsificação,% de transmitância e liberação do fármaco. O estudo de estabilidade foi realizado a 40 °C/75% de umidade relativa. A formulação foi convertida em forma sólida por sua adsorção em Aerosil 300. Os SMEDDS sólidos foram avaliados e comparados com SMEDDS líquidos e a formulação comercializada. O ácido oléico foi selecionado para a fase oleosa, Labrasol como agente tensoativo e Transcutol como co-tensoativo para a formulação de SMEDDS. O lote otimizado mostrou os melhores resultados: menor tamanho de gota (<170 nm), menor tempo de emulsificação (<40 segundos), e de liberação do fármaco (> 85% em 15 min). Além disso, a formulação otimizada manteve-se estável no período de 3 meses. Os SMEDDS sólidos contendo Aerosil 300 apresentaram boas propriedades de fluxo e uniformidade de conteúdo do fármaco. O estudo de difração de raios-X revelou que o fármaco cristalino foi convertido para a forma amorfa, nos SMEDDS sólidos. A velocidade de dissolução do fármaco a partir dos SMEDDS sólidos foi significativamente maior, quando comparado ao fármaco livre e à formulação de comprimidos comercial. Os resultados demonstram o potencial dos SMEDDS como meio para melhorar a solubilidade, a dissolução e, consequentemente, a biodisponibilidade da domperidona.
Subject(s)
Emulsifying Agents/pharmacokinetics , Domperidone/pharmacokinetics , Drug Liberation/drug effects , Solubility/drug effects , Biopharmaceutics/methods , Antiemetics/pharmacokineticsABSTRACT
The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.
O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.