CN101669917B - Scopolamine hydrobromide orally disintegrating microencapsule tablets based on NIMS system - Google Patents

Abstract

The invention relates to the technical field of medicine, and relates to an orally rapidly disintegrating microcapsule tablet of scopolamine hydrobromide based on a "NiMS" system and a preparation method thereof. The oral rapidly disintegrating microcapsule tablet of the present invention is made of scopolamine hydrobromide "NiMS" system and auxiliary materials. Excipients include microcrystalline cellulose, sodium carboxymethyl starch, mannitol, lactose, xylitol, magnesium stearate, micronized silica gel, etc. The scopolamine hydrobromide orally disintegrating microcapsule tablet of the present invention is convenient to take, can disintegrate rapidly through saliva dissolution in the oral cavity, and can be swallowed without drinking water, and the "NiMS" system has a sustained release effect and will not cause drug absorption The abnormally high blood concentration of the drug reduces the side effects of the drug, and can reduce local irritation, and can meet the needs of special conditions and special populations, especially the elderly, children and patients with dysphagia.

Description

A kind of oral rapidly disintegrating microcapsule tablet of scopolamine hydrobromide based on "NiMS" system

technical field

The invention relates to the technical field of medicine, and relates to an orally rapidly disintegrating microcapsule tablet of scopolamine hydrobromide based on a "NiMS" system and a preparation method thereof.

Background technique

Motion sickness is a series of nervous system dysfunction syndromes caused by abnormal exercise stimulation. Its pathogenesis is not yet clear, but it is generally believed that it is closely related to the vestibular system cholinergic hyperfunction. Scopolamine hydrobromide can block M-choline receptors, inhibit the central function, and is mainly used to prevent and treat motion sickness. Scopolamine hydrobromide is odorless and tasteless, and is easily soluble in water. At present, the clinically used dosage forms are mainly oral tablets and injection injections. Many inconveniences, and oral tablets or injections often cause abnormally high blood levels of drug absorption, and the side effects of the drug are large.

The NiMS system is a new technology for drug loading in recent years. After the drug is made into nanoparticles, it is spray-dried and microencapsulated to form a drug-containing NiMS system. It has a slow and controlled release effect, improves its environmental stability, and makes the drug The release of scopolamine hydrobromide is safer and more controllable, and it can be used as an excellent carrier for efficient absorption in specific parts of the gastrointestinal tract after oral administration, but so far there is no relevant information about scopolamine hydrobromide orally disintegrating microcapsules based on the "NiMS" system and its preparation method reports.

Contents of the invention

The invention provides an orally rapidly disintegrating microcapsule tablet of scopolamine hydrobromide based on a "NiMS" system and a preparation method thereof.

The scopolamine hydrobromide oral fast-disintegrating microcapsule tablet based on the "NiMS" system of the present invention is made of the "NiMS" system containing scopolamine hydrobromide and auxiliary materials, and uses chitosan as a carrier to encapsulate scopolamine hydrobromide nano-capsules. The nanoparticle and the drug free in the glue are made of hypromellose as the sustained-release framework material, and the microspheres formed by spray drying technology are the drug-loaded "NiMS" system, in which the content of scopolamine hydrobromide is 0.1 %～1.0% (w/w), made into orally disintegrating microcapsule tablets.

Scopolamine Hydrobromide oral microcapsule tablet component and proportioning (w/w) of the present invention are as follows:

Among them, the drug-loaded "NiMS" system is a "NiMS" system containing 0.1% to 1.0% (w/w) scopolamine hydrobromide;

Wetting agent is microcrystalline cellulose;

The disintegrant is selected from one or more of sodium carboxymethyl starch, lactose, and low-substituted hydroxypropyl cellulose;

The bulking agent is mannitol and/or compressible starch;

The flavoring agent is xylitol;

The lubricant is magnesium stearate;

The flow aid is micropowder silica gel;

The binder is vinylpyrrolidone, which is made into an aqueous solution with a concentration of 1% to 10%;

The preparation method is as follows:

1. Preparation of Scopolamine Hydrobromide "NiMS" system:

I. Preparation of chitosan solution:

Dissolve a certain amount of chitosan and hypromellose in dilute acetic acid, the concentrations of chitosan and hypromellose are both 0.1% to 1% (g/ml), and swell overnight;

II. Preparation of tripolyphosphate solution (referred to as cross-linking agent):

Dissolve sodium tripolyphosphate in distilled water at a concentration of 0.1% to 1% (g/ml), which is a cross-linking agent;

III. Preparation of drug-loaded chitosan nanoparticles:

1. disperse scopolamine hydrobromide in the cross-linking agent prepared by above-mentioned II to obtain a cross-linking agent containing scopolamine hydrobromide; or add scopolamine hydrobromide to the chitosan solution prepared by above-mentioned I to obtain hydrogen-containing Chitosan solution of scopolamine bromate;

2. At 20°C-60°C, with continuous stirring at 300-1000 rpm, slowly add the cross-linking agent prepared in II into the above-mentioned chitosan solution containing scopolamine hydrobromide, or add the above-mentioned hydrogen bromide-containing The cross-linking agent of scopolamine acid is added dropwise in the chitosan solution prepared in I, and the stirring reaction is continued for 10 to 20 minutes to obtain the chitosan nanoparticle suspension containing scopolamine hydrobromide, wherein the scopolamine hydrobromide The concentration is 0.1%-0.5% (g/ml).

IV. Preparation of drug-loaded "NiMS" system:

The scopolamine hydrobromide chitosan nanoparticle suspension prepared in III was spray-dried to make microspheres, and the scopolamine hydrobromide "NiMS" system was obtained.

Two. prepare scopolamine hydrobromide oral microcapsule tablet:

According to the proportion, sieve and mix the "NiMS" system prepared above with microcrystalline cellulose, mannitol, and lactose according to the equal-volume incremental method, then add vinylpyrrolidone aqueous solution for wet granulation, and dry at 50-70°C for 1- After 2 hours, after granulation, add sodium carboxymethyl starch, micropowder silica gel, and magnesium stearate to mix and press into tablets to obtain scopolamine hydrobromide oral microcapsules based on the "NiMS" system.

Through the disintegration time test, the disintegration time is 30-60s, and the release test shows that the cumulative release in 37°C water for 30 minutes is 5%-25%.

The above method provided by the invention can also be used to prepare other drug-loaded "NiMS" systems and oral rapidly disintegrating microcapsules thereof.

The scopolamine hydrobromide orally disintegrating microcapsule tablet of the present invention is convenient to take, can disintegrate rapidly through saliva dissolution in the oral cavity, and can be swallowed without drinking water, and the "NiMS" system has a sustained release effect and will not cause drug absorption The abnormally high blood concentration of the drug reduces the side effects of the drug and reduces local irritation, and can meet the needs of special conditions and special populations, especially the elderly, children and patients with dysphagia.

Detailed ways

Now in conjunction with the examples, the present invention will be further described, but the protection scope of the present invention is not limited to the examples.

Example 1: Preparation of orally rapidly disintegrating microcapsule tablets of scopolamine hydrobromide based on the "NiMS" system

1. Preparation of scopolamine hydrobromide "NiMS" system (referred to as drug-loaded "NiMS" system):

1) prepare the chitosan solution containing scopolamine hydrobromide:

Take 150 mg of chitosan and 90 mg of hypromellose and dissolve them in 300 ml of 0.3% dilute acetic acid to obtain a 0.5% chitosan solution. After swelling overnight, add 80 mg of scopolamine hydrobromide powder to it to make a hydrobromide-containing solution. Chitosan solution of scopolamine acid;

2) Preparation of tripolyphosphate solution:

Prepare a 0.5% tripolyphosphate solution with distilled water;

3) Preparation of scopolamine hydrobromide "NiMS" system:

At 40°C, with continuous stirring at 600 rev/min, the above 0.5% tripolyphosphate solution was slowly added dropwise to the chitosan solution containing scopolamine hydrobromide, and the stirring was continued for 10 minutes to obtain scopolamine hydrobromide Chitosan nanoparticle suspension, the suspension is spray-dried by a spray dryer to make microspheres, which is the scopolamine hydrobromide "NiMS" system.

The encapsulation rate of the obtained "NiMS" system was 93% and the average particle size was 1.2 μm, detected by high performance liquid phase and laser particle size analyzer.

2. prepare scopolamine hydrobromide orally rapidly disintegrating microcapsules, the components and proportioning (w/w) are as follows:

According to the proportion, weigh the drug-loaded "NiMS" system and the total amount of excipients to be 100g, sieve and mix the scopolamine hydrobromide "NiMS" system, microcrystalline cellulose and mannitol according to the method of equal addition, and add the concentration at 5%. Take 20ml of vinylpyrrolidone aqueous solution, carry out wet granulation, dry at 60°C for 1 hour, add sodium carboxymethyl starch, micropowder silica gel, magnesium stearate after granulation, mix well and press into tablets to obtain hydrobromic acid based on the "NiMS" system Scopolamine Oral Microcapsules.

Through the disintegration time limit inspection experiment, the disintegration time limit is 34s, and the release rate test shows that the cumulative release rate in 37°C water for 30 minutes is 7.90%.

Example 2. Preparation of Oral Rapidly Disintegrating Microcapsules of Scopolamine Hydrobromide Based on the "NiMS" System

Get chitosan 150mg, hypromellose 150mg, be dissolved in the dilute acetic acid of 300ml 0.3%, swell overnight, all the other are with embodiment 1. The encapsulation efficiency of the obtained "NiMS" system was 94%, and the average particle size was 1.5 μm.

Example 3.

Prepare scopolamine hydrobromide orally rapidly disintegrating microcapsules according to the following ratio (w/w):

The rest are the same as in Example 1, the disintegration time of the obtained scopolamine hydrobromide orally disintegrating microcapsules is 48 s, and the cumulative release rate in 37° C. water for 30 min is 17%.

Example 4.

Prepare scopolamine hydrobromide orally rapidly disintegrating microcapsules according to the following ratio (w/w):

The rest are the same as in Example 1, the disintegration time of the obtained scopolamine hydrobromide orally disintegrating microcapsule tablet is 45 s, and the cumulative release rate in 30 min in 37° C. water is 21%.

Example 5.

Prepare scopolamine hydrobromide orally rapidly disintegrating microcapsules according to the following ratio (w/w):

The rest are the same as in Example 1, the disintegration time of the obtained scopolamine hydrobromide orally disintegrating microcapsule tablet is 50 s, and the cumulative release rate in 30 minutes in water at 37° C. is 20%.

Example 6.

Prepare scopolamine hydrobromide orally rapidly disintegrating microcapsules according to the following ratio (w/w):

The preparation method was the same as in Example 1. The disintegration time of the obtained scopolamine hydrobromide orally disintegrating microcapsule tablet was 52 s, and the cumulative release rate in 37° C. water for 30 min was 23%.

Claims (1)

1. the scopolamine hydrobromide orally speed based on " NiMS " system collapses microencapsule tablet, and (w/w) is as follows for component and proportioning:

Wherein, medicine carrying " NiMS " system is for containing " NiMS " system of 0.1%～1.0% (w/w) scopolamine hydrobromide;

Drawing humectant is microcrystalline Cellulose;

Disintegrating agent is selected from one or more of carboxymethyl starch sodium, lactose, low-substituted hydroxypropyl cellulose;

Filler is mannitol and/or amylum pregelatinisatum;

Correctives is an xylitol;

Lubricant is a magnesium stearate;

Fluidizer is micropowder silica gel;

Binding agent is a polyvinylpyrrolidone, is made into aqueous solution, and concentration is 1%～10%;

Preparation process is as follows:

1) preparation scopolamine hydrobromide " NiMS " system:

I. prepare chitosan solution:

Certain amount of chitosan and hypromellose are dissolved in the spirit of vinegar, chitosan concentration and

The concentration of hypromellose is 0.1%～1% (g/ml), and swelling is spent the night and got final product;

II. prepare cross-linking agent tripolyphosphate saline solution:

Sodium tripolyphosphate is dissolved in distilled water, and concentration is 0.1%～1% (g/ml), and this is a cross-linking agent;

III. prepare the medicine carrying chitosan nano:

(1) scopolamine hydrobromide is scattered in the cross-linking agent that above-mentioned II makes, must contains the cross-linking agent of hydrobromic acid scopolamine; Or scopolamine hydrobromide added in the chitosan solution that above-mentioned I makes, must contain the chitosan solution of hydrobromic acid scopolamine;

(2) under 20 ℃～60 ℃, continue to stir with 300～1000 rev/mins, II is made cross-linking agent slowly to drip in the chitosan solution that contains the hydrobromic acid scopolamine, the cross-linking agent that maybe will contain the hydrobromic acid scopolamine is added dropwise in the chitosan solution that I makes, continue again to stir 10～20 minutes, promptly get the chitosan nano suspension that contains the hydrobromic acid scopolamine, wherein, scopolamine hydrobromide concentration is 0.1%～0.5% (g/ml);

IV. prepare medicine carrying " NiMS " system:

The scopolamine hydrobromide chitosan nano spray dried for preparing among the III is made microsphere, promptly obtain scopolamine hydrobromide " NiMS " system;

2) preparation scopolamine hydrobromide orally microencapsule tablet:

By proportioning, above-mentioned medicine carrying " NiMS " system and microcrystalline Cellulose, mannitol, lactose, xylitol are sieved behind the mixing by the equivalent method of progressively increasing, add an amount of polyvinylpyrrolidone aqueous solution, carry out wet granulation, dried 1～2 hour for 50～70 ℃, add carboxymethyl starch sodium, micropowder silica gel, magnesium stearate mixing tabletting behind the granulate, promptly get scopolamine hydrobromide orally microencapsule tablet based on " NiMS " system.