CN110623932A

CN110623932A - Captopril tablets and application thereof

Info

Publication number: CN110623932A
Application number: CN201911037810.3A
Authority: CN
Inventors: 林业翔; 王世礼; 宿晓法; 曹欣欣; 薛颖
Original assignee: Tong Ren Pharmaceutical Co Ltd
Current assignee: Tong Ren Pharmaceutical Co Ltd
Priority date: 2019-10-29
Filing date: 2019-10-29
Publication date: 2019-12-31

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and discloses captopril tablets which are prepared from the following raw materials in parts by weight: captopril granules, microcrystalline cellulose, lactose starch mixture, corn starch, stearic acid. The captopril tablet can prolong the action time of the medicine, reduce the medicine taking times and the medicine dosage, reduce the toxic and side effects of the medicine and have good stability.

Description

Captopril tablets and application thereof

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to captopril tablets and application thereof.

Background

Captopril (Captopril), also known as Captopril, is white or white-like crystalline powder of 1- (2-methyl-3-mercapto-1-oxopropyl) -L-proline, which has a peculiar smell similar to garlic, is salty in taste, slightly soluble in water, and easily soluble in ethanol. Captopril is an angiotensin converting enzyme inhibitor (ACE inhibitor or ACEI) and is used in the treatment of hypertension and certain types of congestive heart failure. As the first ACEI class of drugs, captopril is considered a breakthrough in drug therapy due to its new mechanism of action and revolutionary development process. Captopril was first produced by the company Pottem, Mitsunobao, under the trade name of Kablotong.

Captopril is an artificially synthesized non-peptide Angiotensin Converting Enzyme (ACEI) inhibitor, and mainly acts on a renin-angiotensin-aldosterone system. Inhibiting Angiotensin Converting Enzyme (ACEI) of RAAS system, inhibiting angiotensin I conversion or angiotensin II, inhibiting aldosterone secretion, and reducing water and sodium retention. Has obvious blood pressure lowering effect on various types of hypertension, and can improve the cardiac function of patients with congestive heart failure. The hypotensive effect on different renin-typed hypertension patients is characterized by two types of high renin and normal renin; has obvious effect of reducing blood pressure after adding diuretic to the low renin type. The blood pressure lowering mechanism comprises the inhibition of the activity of angiotensin converting enzyme, the reduction of the level of angiotensin II, the diastole of arteriole and the like. Captopril has the effects of lowering blood pressure with light intensity to medium intensity, reducing peripheral vascular resistance, increasing renal blood flow, and accelerating heart rate without being accompanied by reflexive effect. Captopril can lower blood pressure by the following mechanism: inhibiting angiotensin converting enzyme to reduce angiotensin I to AngII, thereby producing vasodilation; simultaneously, the secretion of aldosterone is reduced, so that sodium can be discharged; the specific renal vasodilatation also enhances the sodium excretion function; reduced inactivation of bradykinin due to inhibition of bradykinin hydrolysis; in addition, it can inhibit local angiotensin I formation in vascular tissue and myocardium. Can improve heart function of patients with heart failure. The captopril tablet is rapidly absorbed by oral administration, takes effect in about 15min, reaches the peak value in blood concentration for 1h, is widely distributed, can permeate placenta and can move into milk. The bioavailability is 60%, the protein binding rate is about 30%, T1/2 is 4h, and the effect is maintained for 6 h. Metabolized in the liver, and metabolites and pro-drugs excreted from the urine.

Topril tablets are orally administered 3 times a day, with an initial dose of 25mg generally, increased to 50mg, 3 times a day, and then the effect is preferably observed for 2 weeks with continuous administration. The captopril drug is used independently, the action is violent, the duration is short, and many researchers turn the eyesight to the captopril slow release research, aiming at prolonging the half-life period and reducing the medicine taking times of patients.

Disclosure of Invention

The invention provides a captopril tablet and application thereof in order to optimize prescription captopril tablets.

The invention is realized by the following technical scheme.

The captopril tablet comprises the following raw materials: captopril granules, microcrystalline cellulose, lactose starch mixture, corn starch, stearic acid.

Further, according to 70 ten thousand tablets produced, the raw materials of the captopril tablets comprise the following components: 97.50kg of captopril granules, 21.00kg of microcrystalline cellulose, 21.00kg of lactose-starch mixture, 8.40kg of corn starch and 2.10kg of stearic acid.

Further, the preparation method of the captopril granules comprises the following steps:

1) sequentially adding 30g of glyceryl monostearate and 20g of lecithin into 500ml of ethanol, uniformly stirring, adding 17.5g of captopril, and performing ultrasonic dispersion for 10min to obtain an organic phase;

2) adding Tween-8020 g and chitosan 10g into 500ml of purified water, and performing ultrasonic dispersion for 5min to obtain a water phase;

3) adding the organic phase into the water phase under the stirring condition of 500rpm, wherein the stirring time is 30 min; concentrating under reduced pressure to remove ethanol, and freeze drying to obtain captopril granules.

Preferably, the frequency of the ultrasonic wave is 20 kHZ.

Preferably, the captopril tablet is prepared by the following process: step 1) batching, step 2) mixing, step 3) tabletting and step 4) packaging.

The invention also claims the use of the above described captopril tablets in the treatment of hypertension and congestive heart failure.

Compared with the prior art, the invention has the advantages that the following aspects are mainly included but not limited:

the captopril is firstly wrapped into particles, so that the advantages of avoiding drug degradation, controlling drug release, improving drug stability and the like can be achieved. Compared with the medicines sold in the market, the captopril tablet can prolong the action time of the medicines, reduce the times and the dosage of the medicines and reduce the toxic and side effects of the medicines; the preparation method is simple in preparation process, suitable for large-scale production of enterprises and extremely wide in market development prospect. The captopril tablet provided by the invention has good stability, meets the quality standard of medicines, and can ensure the medication safety of patients.

Drawings

FIG. 1: dissolution profile of different formulations.

Detailed Description

In order to make those skilled in the art better understand the technical solutions in the present application, the technical solutions in the present application will be clearly and completely described below with reference to specific embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The preparation method of captopril granules is as follows:

1) adding 30g of glyceryl monostearate and 20g of lecithin into 500ml of ethanol in sequence, stirring uniformly, adding 17.5g of captopril, and performing ultrasonic dispersion on 20kHZ for 10min to obtain an organic phase;

2) adding Tween-8020 g and chitosan 10g into 500ml of purified water, and performing ultrasonic dispersion with 20kHZ for 5min to obtain a water phase;

The raw material composition of the captopril tablets is as follows 1:

TABLE 1

Process step

1. Ingredients

According to the sequence of auxiliary materials and raw materials, 97.50kg of captopril particles, 21.00kg of microcrystalline cellulose, 21.00kg of lactose-starch complex (the mass ratio of lactose to starch is 85: 15) and 8.40kg of corn starch are weighed in each part, the raw and auxiliary materials are put into a stainless steel barrel lined with a plastic bag, and labels are pasted on the inside and the outside of the barrel. 2.10kg of stearic acid are weighed out and stored separately and added when the total mixing is marked.

2. Mixing

Adding the raw and auxiliary materials except the stearic acid into a three-dimensional motion mixer, setting the swing frequency to be 40, sampling and detecting the mixing uniformity when mixing for 10min, 20min and 30min respectively, and determining reasonable mixing time according to the measurement result. And adding stearic acid with the prescription amount into a three-dimensional motion mixer, setting the swing frequency to be 40 and setting the rotation opening time to be 5 minutes, and uniformly mixing.

3. Tabletting

1) Preparation before production

And checking the operation site and state signboards according to the safety technical operating regulations of tabletting posts. The tablet press dies are replaced with circular dimple dies and the interior surfaces of the equipment are sterilized. Checking that all parts of the tablet press should operate normally. If there is abnormality, it is removed in time.

2) Test machine

And (3) getting qualified captopril tablet total mixed materials from the intermediate station, checking and recording the name, specification, batch number and the like, checking the theoretical tablet weight of the production instruction according to the intermediate product report sheet, and calculating the weight difference range according to the weight difference internal control standard. The pressure of the tablet press is adjusted to the lowest, a start button of the tablet press is pressed, the pressure is adjusted to enable the tablet to be formed and have certain hardness, the weight of the tablet is adjusted to the set weight, and then the pressure is adjusted to 30-70N according to the hardness and the thickness of the pressed tablet. The appearance, hardness, disintegration time, average tablet weight and weight difference of the tablet surface meet the requirements and can be stably produced, a tablet sieving machine is connected at the tablet outlet, and the tablet is pressed at the production speed of 23 revolutions per minute (1500 tablets per minute).

3) Tabletting

During normal production, the disintegration time limit, the hardness and the friability of the tablets should be detected once per shift, the production is continued when the disintegration time limit, the hardness and the friability meet the quality control standard, otherwise, the production is stopped, and the reason is found out. The container card is written, sent to an intermediate station and recorded.

When the tabletting is about to be finished, the disintegration time limit, the hardness and the friability of the tablet need to be detected again, and the production is continued until the end when the quality control standard is met. Writing a material marking card, conveying to an intermediate station and recording.

And after the production is finished, the power supply is turned off, the equipment and the environment are cleaned, remnants in the production process are cleaned, and production records and field cleaning records are filled.

4) The tabletting intermediate control methods and criteria are given in table 2 below.

TABLE 2

Package (I)

Packaging form: and (6) packaging with a plastic bottle.

Main process parameters table 3

Example 2

The captopril particles of the invention are spherical and have uniform size, and the average particle size is between 200 and 300 nm.

Dissolution testing of the inventive captopril tablets:

the control group was commercially available as "BOBU TONG", and the results are shown in FIG. 1. As can be seen from figure 1, compared with the tablet sold on the market, the captopril preparation has a sustained-release effect, prolongs the action time of the medicine, can reduce the frequency and dosage of the medicine, improves the bioavailability and reduces the adverse reaction of the medicine.

And (3) stability testing:

the preparation of the invention is placed at 25 +/-2 ℃ and relative humidity of 60 +/-10%, and is sampled and detected at 0, 3, 6, 9, 12 and 18 months respectively, and the long-term stability of the sample is examined, and the result is shown in table 4.

TABLE 4

Time (moon)	Total impurities%	Maximum single impurity%
			0	0.18	0.05
3	0.25	0.06
			6	0.34	0.07
9	0.39	0.09
			12	0.45	0.10
18	0.48	0.10

It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And such obvious changes and modifications which fall within the spirit of the invention are deemed to be covered by the present invention.

Claims

1. The captopril tablet comprises the following raw materials: captopril granules, microcrystalline cellulose, lactose starch mixture, corn starch, stearic acid.

2. The captopril tablet according to claim 1, wherein the captopril tablet is prepared from the following raw materials in 70 ten thousand tablets: 97.50kg of captopril granules, 21.00kg of microcrystalline cellulose, 21.00kg of lactose-starch mixture, 8.40kg of corn starch and 2.10kg of stearic acid.

3. Captopril tablet according to claims 1-2, characterized in that the captopril particles are prepared as follows:

4. The captopril tablet according to claim 3, wherein the ultrasonic wave has a frequency of 20 kHz.

5. The captopril tablet according to claims 1-4, prepared according to the following process: step 1) batching, step 2) mixing, step 3) tabletting and step 4) packaging.

6. Use of the captopril tablets of claims 1-5 in the treatment of hypertension and congestive heart failure.