Preparation And Simulated Digestion In Vitro Of Coix Seed Oil Tablets Based On Liquisolid Compacts Technique

Coix seed ranks first in the family of Gramineae plants,and has multiple functions in strengthening the spleen and removing dampness,fighting cancer,lowering blood pressure and immune regulation.Coix seed oil(CSO)is the main biologically active component in coix seed and has a significant anti-tumor effect,however,poor water solubility,stability and oral bioavailability limit its use in the food and pharmaceutical fields And development.At present,there are few reports about coix seed oil solid self-emulsifying system and its in vitro simulated digestion.This subject prepared coix seed oil liquid-solid compressed self-emulsifying tablets(LS-CSO-SNEDS)based on the preparation of coix seed oil nano-emulsification system(CSO-SNEDS).In-vitro release and in-vitro simulated digestion were explored,which provided a reference for the research and prediction of the in vitro release and digestion of Coix seed oil solid self-emulsifying tablets.The main research contents and results are as follows:Using CSO as the oil phase,the pseudo-ternary phase diagram and star point design-response surface optimization methods were used to construct the CSO-SNEDS to obtain the optimal formulation of the Tween60/Span20/glycerol/CSO system.The parameters of the determined optimal formula are:the mass fraction of the oil phase is 16.11%,the Km value is 3.54,wherein the composite SA is Tween60/Span20=9:1,and CoSA is glycerin.The appearance of the prepared CSO-SNEDS is a yellow clear liquid,which can form a uniform and stable nanoemulsion after dilution,with an average particle size of 27.52nm,a PDI of 0.188,and a Zeta potential of-15.7mV.The self-emulsifying drug release system is combined with liquid-solid compression technology,and the LS-CSO-SNEDS is prepared by using CSO-SNEDS under the guidance of liquid-solid compression mathematical model.Through the screening experiment of auxiliary materials,calcium silicate was used as the carrier material,and micropowder silica gel was used as the coating material to prepare,and through the screening of R value,the optimization of the amount of disintegrant,the investigation of powder fluidity and tablet related quality,the The formulation was optimized by the determination and the optimal formulation parameters were obtained as follows:R value was 20,CSO-SNEDS was 15g,9.494g calcium silicate,0.475g micropowder silica gel,5%super sodium carboxymethyl starch and 0.2%magnesium stearate.The prepared LS-CSO-SNEDS has smooth and smooth surfaces,an average hardness of 16N,a friability of 0.25%,and a difference in tablet weight of 0.8%,all of which comply with the relevant provisions of the 2015 edition of the Chinese Pharmacopoeia.The experiment also investigated the dissolution of LS-CSO-SNEDS in three dissolution media of water,PBS(pH 6.8)and 0.1M HCl solution.Using reverse dialysis,simulated artificial gastric fluid(SGF)and simulated artificial intestinal fluid(SIF)were used as the release media for the in vitro release experiment of LS-CSO-SNEDS,and five release kinetic models were used for kinetic fitting.The cumulative release of CSO-SNEDS and LS-CSO-SNEDS in SGF and SIF is significantly higher than that of CSO.The LS-CSO-SNEDS prepared by liquid-solid compression technology has improved wettability of CSO compared to CSO-SNEDS And the effective surface area at the time of release,thereby improving its release rate and cumulative release.In short,the LS-CSO-SNEDS prepared by combining the self-emulsifying drug delivery system with liquid-solid compression technology significantly increased the level of CSO release in vitro.The fitting of the release kinetics of CSO-SNEDS and LS-CSO-SNEDS shows that the Ritger-Peppas equation has the highest goodness of fit,which can better describe their release rule in digestive juice.The fitting coefficients of the release of CSO-SNEDS in SIF and SGF are 0.999 and 0.986,respectively,the release kinetic equation in SGF is Q=62.040*t 0.094,and the release behavior in SIF can be expressed as:Q=188.285*t 0.065.The fitting coefficients of LS-CSO-SNEDS in SIF and SGF are 0.986 and 0.988 respectively,the fitting equation in SGF is Q=160.653*t 0.256,and the fitting equation in SIF is Q=229.936*t 0.190.Both release indexes n in SGF and SIF are less than 0.45,which belongs to Fick diffusion mechanism.Using the semi-continuous steady-state gastrointestinal simulation system and the pH-stat method to simulate the digestion experiment,the digestion of LS-CSO-SNEDS and CSO-SNEDS by the saliva,gastric juice and intestinal juice was simulated.Explore LS-CSO-SNEDS,CSO-SNEDS,CSO-MEs by measuring the FFA release curve and changes in particle size and Zeta potential after digestion,and observing the structural changes of the sample in the oral cavity,stomach,and small intestine before and after digestion using an inverted fluorescence microscope,In vitro simulated digestion of CSO direct compression tablets.The results show that the four samples including CSO-MEs and CSO direct compression tablets have no obvious change in particle size and potential after digestion in the oral cavity and stomach,and there is no significant change in morphology.There is a significant change,and under the observation of the fluorescence microscope,the samples all have droplets of different sizes.This morphological change corroborates the sample size and free fatty acid(FFA)release.For the five samples including CSO,the release curve of FFA showed a fast digestion period and a slow digestion period.The release rate of FFA increased rapidly during the first 6 minutes,and then the increase rate slowed down.The FFA release results show that LS-CSO-SNEDS has the highest FFA release rate of 124.03%,followed by CSO-SNEDS with a FFA release rate of 114.14%,CSO-MEs and CSO direct compression tablets have FFA release rates of 98.46%and 82.56%.The above results suggest that LS-CSO-SNEDS can combine the advantages of liquid-solid compression and self-emulsification system to greatly improve the digestion of CSO.