Appllication Of Semi-solid Extrusion 3D Printing Technology To Prepare Directional Drug Release Metronidazole Oral Patch

Recurrent aphthous ulcer is a disease characterized by painful lesions on the oral mucosa and has a high incidence in the population.The onset of recurrent aphthous ulcer is cyclical and prone to recurrence.The patient feels obvious pain during the disease,and in severe cases,it will affect the patient’s mental state and digestive system function.The etiology of recurrent aphthous ulcers is complex,and there is no clear conclusion at present.There are obvious individual differences.During the onset,a round or irregular shape with a diameter of about 5 mm and a grayish-white pseudomembrane redness and swelling will be formed on the oral mucosa.Metronidazole is a nitroimidazole antibiotic commonly used to treat oral diseases such as oral ulcers,gingivitis and periodontitis.The metronidazole patch prepared by the traditional process is a two-way drug release.Due to the flushing effect of saliva,the local utilization rate of the drug is low.3D printing is a rapid prototyping technology that builds three-dimensional entities from digital models,which is highly flexible and can be customized for different needs.In this study,a directional drug release metronidazole oral patch was prepared by semi-solid extrusion 3D printing technology.The oral patch consists of a drug-containing layer and a backing layer,which can improve the local therapeutic effect of the drug.By using the 3D printing applicability,formability,tablet weight of the drug-containing layer,difference in tablet weight,in vitro adhesion,and appearance after drying and swelling as indicators,we screened out suitable drug-containing layers.materials and quantities.The optimal formulation was obtained through formulation optimization: 7%poloxamer 188,10% ethyl cellulose 20,30% carbomer 934 P,28%hypromellose K15 MCR and 25% metronidazole,with an ethanol concentration of 90%.According to the 3D printing suitability,formability,contact angle and mechanical strength of the backing layer paste,the suitable backing layer material and dosage are screened out: 45% ethyl cellulose 100,45%hypromelline Cellulose K15 MCR and 10% triethyl citrate with 90%ethanol concentration.The 3D printed directional drug release metronidazole oral patch was prepared according to the prescription of the drug-containing layer and the backing layer,and the 3D printed patch was verified for directional drug release.The appearance,weight difference,size difference,drug content,dissolution rate and in vitro adhesion time of the 3D printed oral patch all meet the requirements;The experimental results of DSC,FTIR and XRD showed that some metronidazole crystals had undergone crystal transformation;At the same time,preliminary research has been carried out on personalized printing oral patches,which is expected to be customized according to the needs of patients.Finally,the 3D printed oral patch was evaluated for in vitro irritation,and the results showed that the oral patch was less irritating.The oral patch prepared in this study can achieve the directional release of metronidazole,which is beneficial to improve the local utilization of the drug and reduce the side effects caused by drug leakage.At the same time,this study developed a new technical method for the preparation of oral patches,and provided a reference for the research and application of semi-solid extrusion 3D printing technology in oral patches.