Study On Including Cinnamon Volatile Oil By PVP VA64-soluplus Spray-dried Microspheres

Cinnamon volatile oil is a yellow or yellow-brown volatile oil extracted from dried cinnamon bark.It has antipyretic,analgesic,antibacterial,antifungal and other pharmacological effects.The main active ingredient is cinnamaldehyde.Because cinnamon volatile oil has the disadvantages of poor water solubility,easy oxidation,and easy volatility,it has dramatically limited its widespread use in pharmaceutical preparations and the food industry.To increase the stability of volatile oils,cyclodextrin inclusion,porous material adsorption,and microencapsulation are often used for encapsulation and curing.However,these methods include complex inclusion processes,large amounts of excipients,and some components in the body release slowly,stability is weak and cannot be dissolved by water,etc.This project intends to use copovidone and Soluplus as auxiliary materials to prepare water-soluble microspheres by spray drying.The microspheres can contain cinnamon volatile oil through a hydrophobic region composed of the hydrophobic groups of copovidone and Soluplus to achieve inclusion and curing of cinnamon volatile oil the goal of.The specific research content includes the following four parts:1 Preparation and process optimization of water-soluble microspheresTo optimize the preparation process of blank microspheres,the yield of microspheres was used as the index of investigation in this experiment.The single-factor experiment method was used to optimize the formula composition of the micellar solution.The encapsulation rate of the volatile oil of cinnamon was used as the index of investigation.The single-factor experimental method was used to optimize the ratio of excipient drugs.It was determined that the ratio of the blank microspheres to the volatile oil of cinnamon was 8:1.The encapsulation rate of volatile oil was used as the index of investigation.The L 9(3 ~4)orthogonal test method was used to screen the preparation process of micelles.The optimum process was determined to be copovidone-soluplus(mass ratio)12:1 and the concentration0.08 g/m L,water bath temperature 70℃,stirring time 2.5 h;Finally,using the microsphere yield and cinnamon volatile oil encapsulation rate as the indicators of investigation,the L 9(3 ~4)orthogonal test method was used to spray-dry the micelles.The optimum spray drying parameters were determined through screening,such as inlet air temperature of 160℃,outlet air temperature of 80℃,and peristaltic pump speed of 400 m L/h.The optimized process of this research has excellent repeatability and strong feasibility,which lays the foundation for solidifying the volatile oil of cinnamon.2 Evaluation of cinnamon volatile oil microsphere inclusion complexTo evaluate the inclusion complexes of cinnamon volatile oil microspheres,transmission electron microscopy(TEM),scanning electron microscopy(SEM),differential scanning calorimetry(DSC),and X-ray diffraction analysis(XRD)were used to prepare the cinnamon Volatile oil microsphere inclusion complexes were used to characterize the phases:HPLC was used to determine the cinnamaldehyde inclusion rate;shaker method was used to determine the dissolution rate in vitro;60℃stability study was used to investigate the stability.The results showed that the blank microspheres and the microsphere inclusion complexes showed uniform spheroidal structure and uniform dispersion under the TEM observation;both were spherical with a concave surface on the SEM observation;DSC picture of the microsphere inclusion complex Both the endothermic peak and the diffraction peak in the XRD pattern of cinnamon volatile oil disappeared,indicating that cinnamon volatile oil was dispersed and contained in the microspheres in a non-aggregated form;the inclusion rate of cinnamon volatile oil was 98.38%;The cumulative release rate of inclusion compounds was nearly 93.36%,which is close to that of cinnamon volatile oil and higher than that ofβ-cyclodextrin inclusion compound.The stability of the microsphere inclusion compound at 60℃ is significantly lower than that of cinnamon volatile oil andβ-cyclodextrin Inclusion compound.In short,cinnamon volatile oil can be better contained in the hydrophobic region of the microspheres,the stability is improved,and the release rate is less affected.3 Pharmacokinetics of Cinnamon Volatile Oil Microsphere Inclusion ComplexTo compare the differences in bioavailability before and after the inclusion of cinnamon volatile oil,the pharmacokinetic parameters of the cinnamon volatile oil,microsphere inclusion compound andβ-cyclodextrin inclusion compound were determined by HPLC in rats in this experiment.Alltima C18 column(4.6 mm×250mm,5μm),the mobile phase was methanol-0.1%phosphoric acid water(62:38),the detection wavelength was 278 nm,the flow rate was 1 m L/min,and the column temperature was 35℃.Each group of rats was intragastrically administered with a single dose of 50 mg/kg cinnamon volatile oil.Blood was collected from the orbital base venous plexus.Plasma was treated with methanol and entered into HPLC to determine the cinnamic acid content.Pharmacokinetic parameters were calculated using DAS software.After methodological investigation,the linear range of cinnamic acid in the plasma was 0.00303～0.30300mg/ml,and the precision,repeatability,stability and recovery were good,which met the analysis requirements of biological samples.Pharmacokinetic parameters show that the elimination half-life(t1/2z)of microsphere inclusion compound andβ-cyclodextrin inclusion compound in rats is prolonged relative to the essential oil of cinnamon,and the peak drug concentration of microsphere inclusion compound(Cmax)is much higher thanβ-cyclodextrin inclusion compound,the AUC(0-∞) of the three groups of drugs are close,and there is no significant difference.The results showed that the dissolution rate of cinnamon volatile oil was reduced after being encapsulated by microspheres orβ-cyclodextrin.4 Pharmacodynamics Study of Cinnamon Volatile Oil Microsphere Inclusion CompoundIn order to compare the differences in the efficacy of cinnamon volatile oil before and after inclusion,this experiment established a torsion method pain model to evaluate the analgesic effect of cinnamon volatile oil in mice.The experiment consisted of 5 groups,namely cinnamon volatile oil group,microsphere inclusion group,β-cyclodextrin inclusion compound group,blank control group,and aspirin-positive drug group.The blank group was gavaged with the same volume of normal saline.The results showed that cinnamon volatile oil,microsphere inclusion compound andβ-cyclodextrin inclusion compound can significantly reduce the number of writhing in mice and produce a good analgesic effect,the analgesic rates were 53.00%,47.52%,21.15%,the research results show that the analgesic effect of cinnamon volatile oil after microsphere inclusion is slightly reduced,and afterβ-cyclodextrin inclusion is significantly reduced.The results of analgesic experiments show that the inclusion of volatile oil in microspheres will reduce the dissolution of volatile oil in vivo,but the effect is less than that of cyclodextrin inclusion compounds.In summary,the formulation and process parameters of microspheres containing cinnamon volatile oil were optimized.The cinnamon oil microspheres were characterized by using cinnamon oil and cinnamon oil-β-cyclodextrin inclusion compound as controls.In vitro release and stability studies at 60℃,the bioavailability and analgesic effects of volatile oil before and after inclusion were compared.The results show that:Copovidone-Soluplus spray-dried microspheres containing cinnamon volatile oil are beneficial to improve the stability of volatile oil Compared withβ-cyclodextrin inclusion compound,dissolution,blood concentration and analgesic effect of cinnamaldehyde in vivo and in vitro are smaller.Copovidone-Soluplus spray-dried microspheres containing cinnamon volatile oil is a new method to improve the stability of volatile oil,and provides a new idea for the inclusion of traditional Chinese medicine volatile oil.