Eszopiclone-containing particle and its preparation method

Abstract

The invention relates to an eszopiclone-containing particle and its preparation method. The particle can cover the bitter taste of eszopiclone, has no obvious sandy feeling, has uniform contents and high dissolution rate, and can be used for preparing solid dosage forms such as orally disintegrating tablets, dispersing tablets, suspension granules and the like.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to eszopiclone-containing granules and a preparation method thereof. Background technique [0002] Insomnia is a manifestation of sleep disorders. Insomnia not only causes changes in perception and spirit, but also may cause functional diseases and even induce other diseases, which is a great potential threat to human health. At present, nearly 1 / 4 of the people in the world suffer from insomnia, and more than 10% of people in our country have sleep disorders. When insomnia is severe and sleep hygiene and nonpharmacologic treatments are ineffective, drug therapy is the first choice. [0003] Commonly used sedative and hypnotic drugs such as barbiturates and benzodiazepines often have various side effects, such as causing drowsiness, fatigue, dizziness, ataxia, temporary amnesia and disturbance of consciousness. In severe cases, it may lead to coma and respiratory depress...

AI Technical Summary

Problems solved by technology

[0005] However, eszopiclone can produce extremely strong and persistent bitter taste in the oral cavity, and this shortcoming makes the development of oral formulations of eszopiclone greatly limited

Although the common tablets of eszopiclone currently on the market provide a choice for the application of eszopiclone, the disadvantages and limitations of use of conventional common tablets are also very obvious: 1. It cannot effectively cover the bad taste of the drug, causing disintegration The disintegration and drug dissolution time is longer, and the curative effect is slow; although the film-coated tablet has a taste-masking effect to a certain extent, its disintegration and drug dissolution may be worse; 2. The local concentration of the drug after disintegration is high, which may easily cause gastric Intestinal adverse reactions; 3. It must be swallowed whole, and the elderly, children and other patients with dysphagia have poor compliance; 4. The swallowed tablets may stick to the esophagus, causing foreign body sensation or even drug-induced esophageal damage

In conclusion, ordinary tablets are difficult to maximize the application advantages of eszopiclone

CN1418631A discloses a zopiclone orally disintegrating tablet. Although the tablet is dissolved in the oral cavity and is easy to swallow, the disintegrating tablet cannot effectively cover the bitter taste of zopiclone, and patients have a certain sense of rejection

We have found through experiments that this method has the following defects when it is used to prepare eszopiclone granules: 1. Due to the difference in bulk density between eszopiclone bulk drug and excipient powder, it is easy to stratify in a fluidized state, resulting in poor particle content uniformity; 2. The powder of eszopiclone raw material medicine is easy to fly and adhere to the fluidized bed equipment during the fluidization process, resulting in a large loss

We found through experiments that the preparation method of the taste-masking granules also has obvious deficiencies when it is used to prepare the taste-masking granules of eszopiclone: ​​the mixing process before wet granulation is difficult to ensure that the low dose of eszopiclone is mixed evenly with the excipients; The granules produced by the French granulation technology are often irregular in shape, loose in texture, difficult to form a complete coating film at the corners of the granules, and the granules are fragile during the coating process, exposing the inner surface. Achieving better taste-masking usually requires increased coating film thickness, which may result in increased coating time, material and energy costs, and risk of reduced dissolution

However, the composition and preparation method of the pellets are relatively complicated, and the realization method is relatively difficult.

[0011] WO2010116385A describes that eszopiclone can be loaded on an inert carrier (pellets, pellets, balls that do not contain active ingredients), and then taste-masked coating is performed, but no detailed technical scheme and research content are given, so it is necessary to There is still a lot of work to be done to prepare granules with good taste-masking effect by loading eszopiclone on an inert carrier first, and then coating them with taste-masking coating. At the same time, the drug content is uniform and the dissolution rate is good. What conditions should the drug granules meet; how to prepare the drug granules, and screen and optimize the preparation process. Different drug loading methods use different equipment and specific operations, and their advantages and disadvantages are also different. When using drug-containing slurry drug-loading methods, the preparation of drug-containing slurry needs to solve the problem of poor solubility of eszopiclone, particle size selection, etc. question

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