Construction Of Porous Starch Foam Nano-drug Carriers And Its Drug Loading Evaluation For Lovastatin

The oral route of administration due to its safety, effective, simplicity, low price and good compliance for patients is accepted by the public. For low water solubility and high through the membrane characteristics of the BCS II drugs, the dissolution rate is the rate-limiting step of its impact on drug absorption. So the drug formulations improving the dissolution rate become the key to bioavailability of these drugs. This paper aims to build porous starch foam with porous network structure as drug delivery system. The porous connected network structure can decrease the size and crystal degree of drug particle by space restrictions effect and highly dispersed insoluble drugs, thereby accelerating the drug dissolution and enhancing the oral bioavailability of the BCS II class drugs.This article first constructed two kinds of porous starch foam drug delivery system. That is porous starch foam film (PSF) and porous starch foam microspheres (PSM). Soluble starch is the raw material of the two carriers. PSF was prepared by the Gelation-solvent exchange method. SEM images clearly show that PSF with a nanometre porous structure (≤200 nm) is obtained from all the samples. In N2 adsorption/desorption studies, the BET specific surface area and total pore volume are calculated to be 127.75 m2/g and 0.38 ml/g.60% of the BPSF pores have a diameter of 20-80 nm. The PSF FTIR spectra have the peaks at 3000-3500 cm-1 (-OH stretching), which show that BPSF also has a hydrophilic surface with lots of hydrophilic hydroxyl groups. PSM was prepared by the W/O emulsion-freeze thawing method integrating solvent exchange method. SEM images clearly show that particle-size distribution of PSM is 20-100 μm. PSM possess nanometer porous connected structure (< 500 nm). In N2 adsorption/desorption studies, the BET specific surface area and total pore volume are calculated to be 55.572 m2/g and 0.161ml/g.60% of the BPSF pores have a diameter of 20-100 nm. The detection limit N2 adsorption/desorption analyzer is lower 200 nm, the pore (≥200 nm) are ignored. PSM also has a hydrophilic surface. The two carriers have potential as a carrier of insoluble drugs.In order to prepare porous starch foam delivery system and evaluate their in vitro properties, lovastatin was selected as a model drug. UV analysis method for drug content was established. Lovastatin was loaded by immersion/solvent evaporation into PSF and PSM. Combined result of differential scanning calorimetry and X-ray diffraction analysis show that the spatial effect of porous network structure reduces the size and crystal degree and the drug microcrystalline highly dispersed in a carrier system. The FTIR results indicate that the absorption of lovastatin in PSF and PSM is physical. SEM images clearly show that drug adsorbed on the channel and surface. With the increase in the proportion of carrier, superficial drug reduced and the dispersion significantly is improved. In the in vitro dissolution experiments, compared with the raw drug and commercial capsule, the two carriers significantly improved the dissolution of the lovastatin. The long-term stability experiment results showed that the lovastatin in PSF and PSM was stable and had a slight change in crystal degree, but there was no significant change in dissolution behavior.Mobility experimental results of the loaded sample showed that the two particle mobility can be directly filled into capsules and the capsules meet the requirements of relevant standards. In order to verify whether the porous starch foam improve the bioavailability of insoluble drugs, pharmacokinetic studies were performed on Beagle dogs. The results show that the relative bioavailability of LV- PSF capsules and LV-PSM capsules were 133.8±15.694 and 125.9±11.227. The PSF and PSM can increase the oral bioavailability of insoluble drug lovastatin.