| Gastric floating drug delivery systems(GFDDS)have been developed as a new concept to the drug delivery systems based on carrier material,which could float over the gastric contents without affecting the gastric emptying rate and be retained in the stomach for a prolonged period of time to obtain sufficient drug bioavailability.The system has gained enormous attention and its relative researches have become the current hotspot in targeted controlled release drug delivery system in resent years.By reviewing the current research progress of gastric floating carrier material and related drug delivery system,a starch and microcrystalline cellulose natural polysaccharide based composite gel carrier material was developed by the effective method of "dissolution-regeneration" in "green" [Emim][OAc] ionic liquid.After investigated the dissolution and gelatinization behaviors of starch,microcrystalline cellulose and their composite,the relationship between the structures and properties of starch/cellulose composite gel material was established,and a low-density starch/cellulose based composite gel gastric floating drug delivery system was designed.The results showed high academic value and directive significance for the application of natural polysaccharide based gel carrier material in gastric floating drug delivery system.Considering the performance of gel carrier in gastric floating drug delivery system could be affected and regulated during dissolution,[Emim][OAc] ionic liquid was used as effective solvent.By compared the solubilities of Gelose50 starch(G50)and microcrystalline cellulose(MCC)in ionic liquid at different temperatures and in [Emim][OAc]/water mixtures of different ratios,their common conditions for dissolution were obtained.The effects of dissolution with ionic liquid on nano structure,crystalline structure,chain structure of starch and microcrystalline cellulose and their intermolecular interactions in solution were carried out using diverse techniques.Then the mechanism on how the ionic liquid dissolve starch and microcrystalline cellulose was elucidated.The results showed that the anions and cations of ionic liquid synergistically interact with starch and microcrystalline cellulose hydroxyls,and thus cause the breakages of hydrogen bonds in the multi-scale structure,inducing the occurrence of dissolution.With the increasing of concentration of starch/microcrystalline cellulose composite solution,intermolecular interactions occurred between molecular chains of starch and cellulose,their molecules were not isolatedly dispersed and tended to entangle with each other.By a thorough investigation of gelatinization-aggregation behavior of molecular chains of starch,cellulose and their composite in ionic liquid with different anti-solvents and drying method,a systematic relationship was established between the multi-scale structure and properties of gel materials obtained by different solvents.After the dissolution in ionic liquid and regeneration with water,starch/cellulose composite gel material were prepared and the effects of G50/MCC ratio on the structures(network structure,crystalline structure and fractal structure)and properties(texture,digestibility,equilibrium swelling property,floatability)of composite gel materials were investigated.Also,the formation mechanism of composite hydrogel was speculated.The hydrogen bonds between the starch and cellulose chains,chains entanglement and interpenetration,and some orderly aggregation structure were formed during regeneration,leading to the formation of starch/cellulose composite hydrogel.The starch/cellulose composite gel material had porous network structure and some crystalline structure after drying,and showed good enzyme resistance,equilibrium swelling ability and floatability).After that,ranitidine hydrochloride was selected as a model drug to prepare the low-density starch/cellulose composite gel gastric floating drug delivery system using freeze-drying technology.The system achieved simultaneously of remaining buoyant in simulated gastric fluid and sustained drug release by regulating and controling the internal network structure,surface film structure and floatability of starch/cellulose composite gel.The results from in-vitro tests indicated that the optimum system of 3/7 starch/cellulose composite gel material could maintain the buoyancy with a period of 24 h and released ca.45.87% after 1 h and then achieved good sustained and controlled release performance for over 10 h.It was revealed that the release mechanism of the system was coordinative mechanism by Fickian diffusion controlled release and osmotic pressure-driven release.In conclusion,this work involved systematic investigation of the key scientific problems about the estblishment of low-density starch/cellulose composite gel gastric floating drug delivery system based on the "dissolution-regeneration" behaviours in ionic liquid.The structures and properties of starch/cellulose composite gel material were regulated based on the transition of multi-scale structures and molecular interactions of starch,microcrystalline cellulose and their composite during "dissolution-regeneration".A systematic relationship was established between the "dissolution-regeneration" process of starch,microcrystalline cellulose and their composite,and the structures and properties of regenerated gel materials.Also,The key technologies of starch/cellulose composite gel carrier and related gastric floating drug delivery system were achieved based on "dissolution-regeneration" behaviors in ionic liquid and freeze-drying technology.The results provides technical and theoretical supports for the design and development of starch/cellulose composite gel carrier and related gastric floating drug delivery system in ionic liquid. |
PDF Full Text Request