Preparation Of A Novel Mesoporous Composite Silica And Its Evaluation Of Drug Loading And Drug Release

In recent years,it has become a hot issue of pharmaceutical research that how to design the formulation to improve dissolution rate and the bioavailability of water insoluble drug.in addition,the drug loading and drug release rate were be controlled to improve the pharmacodynamics.In view of the above problems,ordered mesoporous carriers can control the drug particle size in nano scale by loading them into the pore channels,to maintain amorphous or microcrystalline state exists in the pores of the carrier,the higher drug specific surface area and dispersion state were also obtained.In addition,the channel connected to each other by the carrier can effectively reduce the resistance of drug release and improve the drug dissolution rate.On account of the weakly acidic drugs with larger treatment doses,functional modification of ordered mesoporous carriers were prepared according to the nature of the drug and dose requirements,which could effectively control of drug loading and drug release rate.Firstly,mesoporous silica cocoon materials(MSNCs)and MgO modified mesoporous silica cocoons(MgO/MSNCs)with cocoon-like hierarchical morphology and different alkalinity are synthesized as the carriers for acid drugs;they were synthesis by one step synthesis method.In other words,the synthesis of mesoporous silica and magnesium oxide were simultaneous,to add the alkalinity of the surface material,mesoporous composite silica materials of acidic drug adsorption by physical adsorption change for chemical adsorption,the surface functionalization was achieved,in order to improve the adsorption capability for acidic drugs,the effective control of drug loading and drug release.Detailed experimental methods was as follows:P123 as a structure-directing agent,n-decane as swelling agent,and hydrochloric acid as the reaction solvent,TEOS and magnesium nitrate were hydrolysis simultaneously by one step synthesis method,the sample was calcined to remove the structure-directing agent P123.According to the results of scanning electron microscopy(SEM),transmission electron microscopy(TEM)and N2 adsorption/desorption experiment,it was found the MSNCs and MgO/MSNCs showed cocoon-like hierarchical morphology.The mesoporous composite silica materials with the pore size of 9.79-16.01 nm and specific surface area of 478.99-524.32 m2/g and pore volume of 1.26-1.77 cm3/g,respectively.At the same time,the prepared carrier with different alkaline by altering molar ratio of precursor solution TEOS and magnesium nitrate.The indomethacin(IMC)was used as a model drug.Crystal transition of drugs was explored by differential X-ray diffraction(XRD)and scanning calorimetry(DSC),and the thermo gravimetric analysis(TGA)and UV spectrophotometer were used for determination of the drug loading amount of MSNCs and MgO-MSNCs to explore the solvent adsorption equilibrium method for loading drug.The XRD and DSC analysis showed that the drug in amorphous state exists in the carrier pore.Five composite silicon carrier MSNCs,0.4MgO-MSNCs,0.6MgO-MSNCs,0.8MgO-MSNCs.and 1.0MgO-MSNCs after the drug loading can be effective in the improvement of insoluble drug dissolution rate.In addition,with the increasing basicity,the release rate of five composite silica carriers of acidic drugs IMC decreased gradually.MgO/MSNCs also have the advantage of adjust the drug release rate by the presence of IMC in the solid formulation due to the increased affinity.And the drug CDTR-PI and CAR were also loaded in the pore of MSNCs and MgO-MSNCs by the solvent adsorption equilibrium method.For the neutral and basic drugs,the composite silica carrier can only significantly increase the dissolution rate than the bulk drugs,but can not play a role in regulating the drug release rate.In order to further study the adsorption drug loading behavior of mesoporous composite silica,the adsorption kinetics and adsorption isotherm behavior was studied to simulate the adsorption process.It can help us to predict the loading capacity of similar model drug,and achieved early anticipation of drug loading capacity,to reduce the blindness of drug loaded procedure.The effect of Mg/Si molar ratio on kinetics and equilibrium of IMC sorption on MgO/MSNCs was thoroughly examined,the increase in the Mg/Si molar ratio resulted in increasing IMC adsorption rate.The adsorption kinetics fitted well with pseudo second-order model.The intraparticle diffusion model indicated that the intraparticle diffusion was not the only rate-limiting step.Compared with the Langmuir isotherm,the Freundlich isotherm showed a better fit,indicating the coverage of IMC on MgO/MSNCs surface was heterogeneous.With increase of the ratio of MgO doped,KF values increase,five kinds of carrier adsorption constants n was greater than 1,and that the adsorption reaction easier.The maximum adsorption capacity of Langmuir was 177.58 mg g-1,233.29 mg g-1,237.11 mg g-1,238.26 mg g-1,and 275.44 mg g-1,respectively.The maximum adsorption capacity of the five carriers to the IMC was calculated by the equation.Temkin equation can further support the IMC adsorption on MgO/MSNCs was a chemisorption process.The active site of mesoporous composite silica was increased by the MgO doped on MSNCs,which makes multimolecular layer adsorption possible.At the same time,the alkalinity of the carrier surface was effective increased by the increased number of MgO functional groups,which makes the adsorption procedure changed from physical to chemical adsorption mainly.Therefore,the drug loading process of IMC not only includes physical adsorption such as van der Waals force,electrostatic force,hydrogen bond,but also includes chemistry adsorption with hydroxyl groups and silanol groups.In conclusion,the similar drug loading procedure was multi molecular layer loading process through the study of three kinds of adsorption model,the largest adsorption capacity of drugs can calculated by the Langmuir equation.As an effective method to predict the drug loading capacity in the early stage,it provides the basis for the prescription design.In view of the mesoporous composite silica carrier with unique drug loading characteristics,the research of multicomponent drug competition mechanism will help us to effectively control the multi drug release order and release rate by changing the nature of the carrier,according to the requirement of actual clinical medication.In order to comprehensive study the unique drug absorption characteristics on composite silica carrier,the acidic drugs IMC,neutral drug CDTR-PI and basic drugs CAR were selected as a model drug,to further explore competitive adsorption process.The results showed that,the adsorption rate of IMC fastest,and then CDTR-PI,finally CAR.Scatchard research showed that the acidity effect is the main factors affecting the order of adsorption.There are two kinds of different recognition sites in the carrier,which can play an important role in the carboxyl group of IMC,and in the process of adsorption and the combination of drugs in two different ways.So the release rate of IMC was slow,while CDTR-PI and CAR showed the fast release rate.In summary,insoluble drug was maintain highly dispersed state controlled by mesoporous composite silica carrier,which simultaneously improved the dissolution rate and effective controlled the loading capacity and release rate of the acidic drug.The research of drug-loaded mechanism can help us to effectively control the drug release behavior from multi-components drug by adjust the properties of the carrier,which provides the basis for the initial preparation of the compound prescription design.