Preparation Process Of Mirtazapine Masked Orally Disintegrating Tablets And Its Quality Evaluation

Appetite loss is one of the clinical symptoms of a pet’s illness,and relieving it has a significant role in the treatment of the disease.Mirtazapine(MRZ),a tricyclic antidepressant,has been used as an appetite stimulant in the pet clinic,and the preparation of this medication is still vacant in the veterinary clinic in China.Orally disintegrating tablets are a new type of tablet dosage form,which has the advantages of fast absorption,high bioavailability and low irritation to the mucous membrane of the digestive tract compared with ordinary preparations.However,the problem of palatability of orally disintegrating tablets is its disadvantage.The drug coating technology is known as the simplest and most direct taste masking technology,which is based on the principle of wrapping the periphery of the drug with polymeric materials to block the release of the drug in the mouth and thus play a role in taste masking.For this purpose,in this study,orally disintegrating tablets containing microspheres were prepared by combining drug coating technology with orally disintegrating tablet preparation process;in addition,by exploring the prescription process study of microspheres and orally disintegrating tablets in the laboratory stage,microspheres were prepared by emulsification-solvent diffusion method and orally disintegrating tablets were prepared by direct compression method,in vitro analysis methods for microspheres and orally disintegrating tablets were established,and the developed The quality of the developed microspheres and orally disintegrating tablets was studied to provide a theoretical basis for the subsequent production.At the same time,the tastemasking effect of the tablets was investigated by a double-basin test.(1)Establishment of a method for the determination of mirtazapine contentFirstly,an in vitro assay for MRZ of two dissolution media was established by UV spectrophotometry to set the microsphere quality screening conditions,including yield,encapsulation rate and drug loading capacity.After that,single-factor test was used to screen the optimal preparation process conditions in terms of yield,encapsulation rate,drug loading capacity and cumulative dissolution rate,i.e.,drug to polymer ratio of 3:2,polymer concentration of 6%,emulsifier of 2% of poloxamer 188,and rotational speed of 500 rmp.The final microsphere yield was 78.19±0.39%,encapsulation rate was 93.19±0.71%,drug loading capacity The drug yield was 55.91±0.43%,the microsphere diameter was 106.12±1.49 μm,the cumulative dissolution rate was 2.46% in PBS for 5 min,and the cumulative release rate was100% in 0.1 M HCL solution for 20 min.In addition,the results of quality investigation showed that the surface of microspheres was smooth and round,without adhesion,with small permeable pores;there was no covalent interaction between MRZ and ethylcellulose(EC)during the preparation of microspheres,but only a simple wrapping relationship;the stability of microspheres was good as shown by high temperature,high humidity and light test.(2)Preparation and quality evaluation of mirtazapine orally disintegrating tabletsFirstly,an in vitro assay of MRZ was established by high performance liquid chromatography for the determination of MR in mirtazapine orally disintegrating tablets.Mirtazapine microspheres were prepared according to the above optimized conditions,and then The optimal filler,disintegrant and lubricant for orally disintegrating tablets were screened by single-factor test,which were mannitol,cross-linked povidone,talc and magnesium stearate,respectively.The four factors of microcrystalline cellulose,cross-linked povidone,talc,and magnesium stearate were designed by orthogonal optimization test at three levels.The optimal prescription was: microspheres 3.5 mg,microcrystalline cellulose 42 mg,mannitol 42.5 mg,cross-linked povidone 8 mg,aspartame 2 mg,talc 1.5 mg,and magnesium stearate 0.5 mg.The results of the quality study of mirtazapine orally disintegrating tablets showed a disintegration time of 20.22±0.46 s,a hardness of 4.04±0.04 kg,a fragility of 0.078±0.004%,and a dissolution degree close to 100%;the uniformity and reproducibility of the three batches of mirtazapine orally disintegrating tablets were good,and the MRZ content and disintegration time did not change significantly after the stability test;the cumulative release was 1.39% in PBS for 3 min and complete in 0.1M HCL solution for 20 min.The results of the similarity test between mirtazapine orally disintegrating tablets and microspheres showed that the release profiles of both in the two dissolution media were similar,and the release behavior of microspheres was still retained in mirtazapine orally disintegrating tablets.The results of the accelerated test examination suggest that mirtazapine orally disintegrating tablets should be packaged separately to avoid the effects of high temperature,and attention should be paid to moisture protection during transportation and storage.(3)Taste masking and appetite stimulating effects of mirtazapine orally disintegrating tablets on catsThe taste-masking effect was evaluated by the double-basin test,and the taste-masking effect of mirtazapine orally disintegrating tablets prepared in this study was significant compared with that of non-masked mirtazapine orally disintegrating tablets,and the consumption of food in the basin of mirtazapine taste-masking orally disintegrating tablets was significantly reduced with significance(p < 0.05).The results of appetite stimulation test showed that mirtazapine orally disintegrating tablets possessed effective appetite stimulating effect,and this appetite stimulating effect did not originate from the excipient component of orally disintegrating tablets.In conclusion,this study prepared mirtazapine orally disintegrating tablets with good taste masking effect and qualified quality,which can provide a laboratory basis for future batch development,promote further promotion of microencapsulated drug formulations in veterinary clinics,and hopefully alleviate the current situation of low medication adherence in pets.