ABSTRACT
Objective To prepare and characterize ginkgolide K-loaded mPEG-PLGA [poly (D,L-lactide-co-gly-colide)-block-poly (ethylene glycol)] polymer nanoparticles (GK-mPEG-PLGA-NPs) and to evaluate its neuroprotective effect on the H2O2-induced PC12 cells injury in vitro. Methods The PLGA-PEG-COOH polymer was selected as carrier and double emulsion solvent evaporation technique was employed to prepare the stealth nanoparticles. The encapsulation efficiency (EE) and drug load (DL) of GK-mPEG-PLGA-NPs were investigated by HPLC. The size distribution, zeta potential, and surface morphology of GK-mPEG-PLGA-NPs were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The in vitro release of GK-mPEG-PLGA-NPs was examined using phosphate buffer solution (pH 7.4) as the releasing medium for 24 h. The H2O2-induced PC12 cells injury models was established for the investigation of the protective effect of GK-mPEG-PLGA-NPs on nerve cells in vitro. Results EE and DL of GK-mPEG-PLGA-NPs was (83.40 ± 2.85)% and (3.26 ± 0.24) mg/g, respectively. The average diameter of GK-mPEG-PLGA-NPs was (93.19 ± 2.77) nm and zeta potential was (-11.93 ± 1.71) mV. The cumulative rate of drug release was (90.5 ± 4.0)% after 60 h in phosphate buffer solution. GK-mPEG-PLGA-NPs significantly inhibited the apoptosis of PC12 cells and the release of lactic dehydrogenase induced by H2O2. However, the protective action of GK-mPEG-PLGA-NPs on the H2O2-iduced PC12 cells injury was significantly weaker than that of GK. Conclusion Our results proved that GK-mPEG-PLGA-NPs had a sustained release behavior in vitro and the neuroprotective effect of GK-mPEG-PLGA-NPs on H2O2-induced PC12 cells, which indicates that GK-mPEG-PLGA-NPs has the prospect of application and deserves further research. Key words: ginkgolide K; mPEG-PLGA; in vitro release; in vitro neuroprotection; d
ABSTRACT
In recent years oral controlled delivery systems have gained increased importance and interest since it is necessary to improve the systemic absorption of the drugs and patient compliance. In addition, controlled delivery systems maintain uniform drug levels, reduce dose and hence dose related side effect, and increase the safety margin. The objective of present work was prepared sustained release solid dispersion of Metoclopramide HCl by solvent evaporation method. Several polymers like combination of Eudragit RSPO - Eudragit RLPO and Guargum-Egg albumin as synthetic and natural polymers respectively were used. Several parameters like Solubility, Partition coefficient, Drug content, Percent drug release, Bulk density, Tapped density and Carr’s index were evaluated and all parameters were found to be in acceptable range. The results of XRD and SEM analysis were showed that the drug was converted into a solid dispersion. The In vivo studies were performed on Albino Wistar rats and various pharmacokinetics parameters were determined. The whole study was showed that the solid dispersion of Metoclopramide HCl sustained the release rate of drug for a prolong period of time at least 12 hrs and shows to increase the bioavailability and simultaneously decrease the dosing interval as well as dosing amount. The formulation minimizes the blood level oscillations, dose related adverse effects and cost and ultimately improve the patient compliance and drug efficiency.
ABSTRACT
Objective: To apply the response surface-central composite design to developing and optimizing the oral fast disintegrating tablets (ODT) formulation for Jiawei Qing'e, a kind of prescription of Chinese herbal medicine. Methods: The bitterness of Jiawei Qing'e was masked using Eudragit E-100 by solvent evaporation technique. Response surface approach was applied to investigating the interaction of formulation parameters in optimizing the formulation. The independent variables were Eudragit E-100/drug ratio (X1), amount of disintegrants (X2), and the amount of diluents (X3). The disintegration time (Y1), hardness (Y2), and weight variations of the tablets were characterized. Results: The models predicted levels of X1 = 4.63%, X2 = 5.25%, and X3 = 34.33%, for the optimal formulation having a hardness of 3.0 kg with the disintegration time of 30 s within experimental region. The observed response of Y1 = 26.5 s and Y2 = 3.14 kg reasonably agreed with the predicted response. Conclusion: Response surface methodology shows the good predictability and reliability in optimizing the formulation. The optimized ODT of Jiawei Qing'e has acceptable taste, rapid disintegrating ability, and good mechanical strength. © 2013 Tianjin Press of Chinese Herbal Medicines.
ABSTRACT
Solis dispersions (SDs) traditionally have been used as effective methods to improve the dissolution properties and bioavailability of poorly water-soluble drugs. Diclofenac Sodium, a non steroidal anti-inflammatory drug with analgesic and anti-inflammatory property was selected as the model drug. The poor aqueous solubility of the drug results in variable dissolution rate and hence poor bioavailability. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, diclofenac sodium, by SD technique as using Eudragit E100. SD was prepared by solvent evaporation technique. The SD was characterized for particle size, particle size distribution and solubility studies. Solid state characterizations i.e., Differential Scanning Calorimetry and Scanning Electron Microscopy were also carried out for the best formulation. It was concluded that the SD prepared by solvent evaporation technique using Eudragit E100 enhanced solubility and dissolution and hence better patient compliance and effective therapy.
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OBJECTIVE: To prepare microspheres for nasal delivery by emulsification solvent evaporation technique using water-soluble carboxylation chitosan as the drug carrier, thus to avoid using stimulatory and toxic aldehydes crosslinkers and acid solvent which are used by the traditional method. METHODS: Zolmitriptan (ZT) was used as the model drug to prepare the carboxylation chitosan microspheres. The prescription and technology were optimized to prepare the microspheres. The yield, particle sizes, appearance, drug loading, encapsulation efficiency and drug release of the microspheres were evaluated. RESULTS: The microspheres prepared by the optimized method were spherical, smooth, and free flowing. The particle sizes of the microspheres were well-distributed and the mean particle size was (21.4±10.1)μm. The drug loading was 5.67% and the encapsulation efficiency was 62.4%. The in vitro release study of the microspheres showed that the drug was sustainedly released and could be released for about 85% in 8 h. CONCLUSION: It is feasible to prepare carboxylation chitosan microspheres for nasal administration by emulsification solvent evaporation method, avoiding the use of aldehydes crosslinkers and acid solvent.
ABSTRACT
The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug by a solid dispersion technique, in order to investigate the effect of these polymers on release mechanism from solid dispersions. Diazepam was used as a model drug to evaluate its release characteristics from different matrices. Solid dispersions were prepared by using polyethylene glycol 6000 (PEG-6000), HPMC, HPC and Poloxamer in different drug-to-carrier ratios (1:2, 1:4, 1:6, 1:8, 1:10). The solid dispersions were prepared by solvent method. The pure drug and solid dispersions were characterized by in vitro dissolution study. Distilled water was used as dissolution media, 1000 ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37°C and a paddle speed of 100 rpm. The very slow dissolution rate was observed for pure Diazepam and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. SEM (Scan-ning Electron microscope) studies shows that the solid dispersion having a uniform dispersion. Solid dispersions prepared with PEG-6000, Poloxamer showed the highest improvement in wettability and dissolution rate of Diaze-pam. Solid dispersion containing polymer prepared with solvent method showed significant improvement in the release profile as compared to pure drug, Diazepam.
ABSTRACT
Microspheres ketoprofen (KP) were prepared by o/w emulsion solvent evaporation technique using Eudragit®RS100 as a polymeric material. The effect of process variables such as drug: polymer ratio, stirring rate, emulsifier concentration, internal organic solvent and dispersing medium volumes were examined. The prepared formulations were characterized for particle size distribution, percent yield, entrapment efficiency, in vitro release and in vivo studies behavior. The study revealed that the mean particle size ranged from 293.06 to 438.63 μm, the KP loading efficiency varied from 60.19-87.63% of the theoretical amount incorporated, all microspheres patches exhibited a prolonged release for almost 24 hrs and the release pattern was diffusion model. The pharmacokinetic parameters, Cmax, Tmax, AUC0-24 and AUC0-∞ were calculated from the plasma drug concentration-time data. Plasma KP concentrations and pharmacokinetics parameters were statistically analyzed. The test formulation exhibited controlled and prolonged absorption (Tmax) of 6.79 ± 0.0.39 vs. 2.03 ± 0.08 and 3.32 ± 0.24 hs; Cmax of 14.42 ± 0.50 vs. 18.78 ± 0.95 and 16.58 ± 1.02 μg/ml) when compared to the plain drug and marketed product, respectively. In-vivo studies revealed that the relative bioavailability of the KP increased by more than 1.3 times by formulating it into microspheres compared to plain drug.
ABSTRACT
The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug by a solid dispersion technique, in order to investigate the effect of these polymers on release mechanism from solid dispersions. Diazepam was used as a model drug to evaluate its release characteristics from different matrices. Solid dispersions were prepared by using polyethylene glycol 6000 (PEG-6000), HPMC, HPC and Poloxamer in different drug-to-carrier ratios (1:2, 1:4, 1:6, 1:8, 1:10). The solid dispersions were prepared by solvent method. The pure drug and solid dispersions were characterized by in vitro dissolution study. Distilled water was used as dissolution media, 1000 ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37°C and a paddle speed of 100 rpm. The very slow dissolution rate was observed for pure Diazepam and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. SEM (Scan-ning Electron microscope) studies shows that the solid dispersion having a uniform dispersion. Solid dispersions prepared with PEG-6000, Poloxamer showed the highest improvement in wettability and dissolution rate of Diaze-pam. Solid dispersion containing polymer prepared with solvent method showed significant improvement in the release profile as compared to pure drug, Diazepam.