Ramelteon sublingual tablets and preparation method thereof

Abstract

The invention relates to ramelteon sublingual tablets. The ramelteon sublingual tablets comprise the following materials in percentage by weight of 0.1%-0.5% of ramelteon, 95%-97% of a filler, 3%-5% of a disintegrating agent, 0.05%-0.5% of a lubricating agent and 0.05% of a corrigent. The ramelteon sublingual tablets provided by the invention are good in taste, good in stability, good in content uniformity, short in disintegration time limit, and capable of avoiding the first-pass effect of the liver and greatly improving the compliance of a patient; and compared with ramelteon oral tablets, the ramelteon sublingual tablets are higher in relative bioavailability and are greatly superior to ramelteon sublingual tablets which are researched and developed originally.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a ramelteon sublingual tablet and a preparation method thereof. Background technique [0002] Ramelteon (Ramelteon, ) is an oral hypnotic drug developed by Takeda Corporation of Japan, and it is the first melatonin receptor agonist used in the clinical treatment of insomnia. Ramelteon has high selectivity, has high affinity with melatonin receptors MT1 and MT2 receptors, and has a specific and complete agonistic effect on MT1 and MT2 receptors, but does not interact with MT3 receptors. In addition, it does not bind to neurotransmitter receptors such as GABA receptors, and does not interfere with the activity of most enzymes to a certain extent, so ramelteon has a low potential for abuse and can avoid the distraction associated with GABA drugs (may lead to car accidents, falls, fractures, etc.), drug addiction and dependence. Ramelteon has been launched in the United...

AI Technical Summary

Problems solved by technology

But its disadvantages are: 1. The preparation process involves steps such as wet granulation and drying, which is cumbersome and time-consuming, and the preparation cost increases; 2. Ethanol is used as a solvent in wet granulation, which has hidden dangers of "three wastes" discharge and production safety; 3. The granules obtained after French granulation are hard, which affects the taste and the compliance of sublingual administration is poor

[0007] The Chinese patent with publication number CN 103429223A (Original Research Takeda) discloses a preparation for oral mucosal absorption of ramelteon, including sublingual administration or buccal administration, and Example 2 in the description is 0.25 mg Ramelteon sublingual tablet, its adjuvant consists of binder (pregelatinized starch), excipient (D-mannitol+microcrystalline cellulose), disintegrant (crospovidone), lubricant ( Sodium stearyl fumarate), the weak point of this technical scheme is: 1. microcrystalline cellulose and pregelatinized starch in the prescription are all water-insoluble adjuvants, and mouthfeel will be affected (there is gritty feeling) during sublingual administration ), and there is no flavoring agent in the prescription, so the patient's compliance is poor; ②It is prepared through fluidized bed granulation, coating and other processes, and the filler D-mannitol is used in both coating and granulation , its dosage is between 70% and 80%, not above 95%

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