| With the improvement of the level of biomedicine,the form of administration is no longer limited to capsules,tablets,liquid dosage and intravenous injection.The efficiency of drug delivery and bioavailability can be improved by reducing the intake and release more pharmaceutical excipients at designated locations.A new type of oral fast-dissolving film(ODF)can be used for some drugs that can be absorbed through the oral mucosa and need to take effect quickly.It can be applied to the situation that need not take a lot of water and has difficulty in swallowing.It also reduces the first-pass effect of the gastrointestinal tract,and get released into the blood circulation quickly through oral mucosal absorption to take effect.For some enteric drugs that need to act on the intestinal tract,p H-sensitive materials can be used to coat and protect the drug when it passes through the stomach with p H=2.1,and swell to release the drug when it reaches the intestinal tract with p H=7.4.As a drug-loading matrix,it not only needs to have good biocompatibility,biodegradability,no immunogen,non-toxic and harmless,but also meet the requirements of mechanical properties,physical and chemical properties and special properties,such as good mucosal adhesion.At present,the use of polymer materials as drug-loading matrix is a research hotspot in this field,because of its stable physical and chemical properties,and the release rate of the drug can be adjusted by changing the composition of the carrier material or the preparation method.Hypromellose(HPMC)and sodium alginate(SA)have been approved as medicines by the FDA and also materials listed in the Chinese Pharmacopoeia that can be used as pharmaceutical excipients.They can be dissolved in water and also easily processed and molded.In the result,they are commonly used as drug carriers.Therefore,this thesis focus on SA and HPMC to prepare drug-loading films that can be applied to oral disintegration and skin-shell gel fibers which is p H-sensitive for encapsulating enteric drugs.Explore the component ratio and preparation methods to obtain better physical and chemical properties and drug-carrying properties.The specific research content includes:(1)Prepare HPMC/SA oral quick-dissolving film by casting,change the composition of the film,and introduce plasticizers and active pharmaceutical substances(API).Analyze the molecules of the film agent by Fourier Infrared Spectrometer(FTIR),Cold Field Emission Scanning Electron Microscope(FE-SEM),Ultraviolet Spectrophotometer(UV-Vis),Netzsch Thermogravimetric Analyzer(TGA)and Universal Material Testing Machine Structure,morphology and structure,test various properties and conduct water solubility test.The best film-forming agent ratio in the experimental range is HPMC:SA=3:1.When sorbitol(Sor)with a mass fraction of 0.05% of the film-forming agent is added as a plasticizer,the elongation at break of the composite film The rate and its increase rate were 14.9% and 49% respectively,and maintained good water solubility.Select optimized film-forming components,and load benzydamine hydrochloride(BH)with a mass fraction of 10%-50% of the film-forming agent to prepare HPMC/SA@BH,and determine the actual drug loading and drug crystallinity.The research results show that the film can effectively inhibit BH crystallization and improve its utilization;but the mass of BH loaded must not exceed 40% of the film-forming agent,otherwise the dispersion will not be uniform and the drug loading efficiency will be reduced.(2)The HPMC/SA@ASP skin-shell gel fiber with SA hydrogel as the shell layer,HPMC as the skin layer and loaded with acetylsalicylic acid(ASP)was prepared by using a microfluidic spinning machine.Through the orthogonal experiment method,the elongation at break,the tensile strength and the swelling rate are used to evaluate the index,mainly to investigate the effect of the shell concentration(sodium alginate),the skin layer concentration(hydroxypropylmethyl cellulose),and the speed ratio of skin-shell solution extrusion,in order to explore the factors affecting the preparation and obtain the optimized preparation conditions.FTIR,SEM,UV-Vis,and fluorescence microscope were used to test and analyze the molecular structure,morphology and structure,calculate the drug release rate,and determine the swelling rate.The toughness and strength of HPMC/SA@ASP skin-shell gel fiber mainly depend on the concentration of SA spinning solution.The higher the concentration of SA spinning solution,the greater the elongation at break and the lower the tensile strength.The more obvious the encapsulation effect in the intestinal fluid,the higher the swelling rate in the simulated intestinal fluid and can delay the degradation time.When the HPMC spinning solution concentration is 3%,the SA spinning solution concentration is 4%,and the flow rate is 10 m L/h,the tensile strength and elongation at break are 30.98 MPa and 45.18%,respectively;in the simulated gastric juice at p H=2.1 The swelling rate was 71.62% after 2h of medium treatment,and the swelling rates of 15 min and30min treatment in simulated intestinal juice with p H=7.4 were 547.86% and 718.57%,respectively,which showed well p H sensitivity and swelling property;drug release rate within15 min It is 28.6%,which can effectively alleviate the sudden release phenomenon. |
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