KR20130023127A - Controlled-release formulations comprising pregabalin - Google Patents

Abstract

PURPOSE: A sustained-release formulation containing pregabalin is provided to stably and continuously release pregabalin and to ensure an anti-seizure property. CONSTITUTION: A sustained-release formulation contains pregabalin and one or more selected among a swelling agent, a matrix forming agent, and a vapor generating agent. The matrix forming agent is hypromellose. The viscosity of the matrix forming agent is 4000-150000 cps. The swelling agent is sodium starch glycolate. The vapor generating agent is sodium bicarbonate. [Reference numerals] (AA) Embodiment 1; (BB) Comparative embodiment 2; (CC) Comparative embodiment 3

Description

Sustained-release preparations containing pregabalin {CONTROLLED-RELEASE FORMULATIONS COMPRISING PREGABALIN}

The present invention relates to a sustained release formulation containing pregabalin suitable for once-daily administration.

Pregabalin is a drug that has anti-seizure efficacy, as described in US Pat. No. 5,563,175 (RB Silverman), which includes epilepsy, pain, physiological symptoms associated with psychomotor stimulants, inflammation, gastrointestinal damage, alcoholism, It is useful for treating insomnia, fibromyalgia, and various mental disorders including anxiety, depression, mania and bipolar disorder. Pregabalin has been approved in the United States for the treatment of diabetic peripheral neuropathy, postherpetic neuralgia, and partial early seizures in adults. Pregabalin is available in immediate release (IR) formulations of capsules and is administered to patients twice daily or three times daily (BID or TID).

However, if pregabalin, which is administered twice or more daily, for such symptom, can be administered once daily (QD), the patient's drug compliance can be improved and the drug concentration in the blood can be kept constant. Because it can reduce drug side effects, there is an advantage that can sustain the effect of the drug.

In general sustained-release preparations, the average absorption time of the drug is about 6 to 8 hours, so it is difficult to expect the desired drug efficacy only once a day. Therefore, in order to develop a pregabalin formulation that can be taken once daily, a special formulation design of the formulation that can prolong the absorption time of the drug is required.

Formulation design systems used in sustained release formulations include swelling systems, flotation systems, biofilm attachment systems, and the like. Polyethylene oxide, which is a matrix-forming agent used in a conventional swelling system, has a problem of low swelling, which can withstand external resistance after swelling, although swelling is good. US Patent Publications US6340475 and US6488962 describe swelling systems containing polyethylene oxide and xanthan gum. The polymer used in such a swelling system has a low resistance after swelling, and there is a risk that the form of the preparation may be rapidly collapsed by the gastrointestinal movement. Korean Journal of Pharmaceutical Sciences (2009) Vol. 39, No. 4 discloses the preparation of swellable gastric suspension tablets by preparing a swellable tablet and then coating a semipermeable membrane on the tablet surface. The system has the disadvantage that the semipermeable membrane is damaged by the movement of the gastrointestinal tract, making control release impossible.

In addition, conventional flotation systems have a disadvantage in that suspension is not achieved within a short time (within about 30 minutes after administration) due to relatively dense main components and other additives.

On the other hand, the biofilm attachment system is difficult to maintain due to the movement of the gastrointestinal tract and the food, there is a problem that the actual product is not made.

U.S. Patent 5,563,175 United States Patent Application Publication No. US6340475 United States Patent Application Publication No. US6488962

Journal of Pharmacology, Vol. 39, No. 4

The present invention is to provide a sustained release formulation of pregabalin, which is formulated so as to obtain a desired effect even if the pregabalin is administered only once a day.

The present invention provides a sustained release preparation comprising a pregabalin or a pharmaceutically acceptable salt thereof as an active ingredient, further comprising at least one of a swelling agent, a matrix forming agent, and a gas generating agent. .

According to one embodiment of the present invention, the matrix forming agent is preferably hypromellose.

According to another example of the present invention, the viscosity of the matrix forming agent is preferably 4000 to 150000 cps.

According to another example of the present invention, the swelling agent is sodium starch glycolate, the gas generator is preferably sodium bicarbonate.

According to another embodiment of the present invention, the swelling agent is 2 to 8% by weight, the matrix forming agent is 20 to 35% by weight, the gas generator is 4 to 10% by weight based on the total weight of the sustained-release formulation desirable.

According to another example of the invention, the sustained release formulation is suspended in a solution of pH 1.2 to pH 4.0 within 30 minutes, it is preferable that the suspension is maintained for 5 hours to 24 hours.

According to another example of the invention, the sustained release formulation preferably increases by 1.5 to 2 times the total volume of the initial sustained release formulation within 1 hour in a solution of pH 1.2 to pH 4.0.

The sustained-release preparation according to the present invention allows the pregabalin to be released stably and continuously, thus achieving the desired effect even if administered only once a day.

Figure 1 is a graph showing the dissolution rate with time of Example 1 and Comparative Examples 2,3.
Figure 2 is a graph showing the time-blood concentration in the beagle dog of Example 1 and the control drug (Pfizer, Lyrica). In the graph, Reference is an empirical result from the first group (control), and Test is a test result from the second group (Example 1).

The present invention relates to a sustained-release preparation containing pregabalin or a pharmaceutically acceptable salt thereof as an active ingredient, and further comprising a sustained-release preparation further comprising at least one of a swelling agent, a matrix former, and a gas generator. do.

The pregabalin sustained release preparation of the present invention may include one or more of a swelling agent, a matrix former, and a gas generator, and preferably includes all of the swelling agent, the matrix former, and the gas generator. When only the swelling agent and the matrix-forming agent are used for the pregabalin, the size of the pylorus and the gastric emptying time (GET) are individually different due to the characteristics of each patient, so that the preparation may pass through the pylorus before the preparation is sufficiently swollen. There is a risk that a safer gastroretentive system is required to achieve the purpose of once-daily administration, and in addition to the swelling agent and matrix former of the present invention, a formulation comprising a gaseous agent is sufficiently swelled before the pylorus Pass it through.

Pregabalin of the present invention (Pregabalin) may be prepared using known methods. In some of these methods, a racemic mixture of 3-aminomethyl-5-methyl-hexane is synthesized and subsequently degraded to its R- and S-enantiomers. Pregabalin of the present invention may be an enantiomer of R- or S-, and the pharmaceutically acceptable salt of the pregabalin of the present invention may be a known alkali or acid salt.

The swelling agent of the present invention means a component that allows swelling in a short time, cross-linked polyvinylpyrrolidone, croscarmellose sodium, sodium starch glycolate and the like can be used, but is not limited thereto.

The swelling agent is preferably contained 2 to 8% by weight relative to the total weight of the formulation according to the invention. When the amount of the matrix forming agent is less than 2% by weight, the matrix forming agent can not be expanded due to the high viscosity. In the case of exceeding 8% by weight, the matrix system may be destroyed due to excessive swelling.

The matrix forming agent means a component used for the purpose of forming a matrix of a sustained release pharmaceutical formulation. The matrix forming agent compensates for the disadvantage that the sustained-release pharmaceutical preparation has a low resistance after swelling in vivo and thus shortens the residence time in the stomach. Preferably, the matrix forming agent is preferably a high viscosity formulation with high rigidity. As the matrix forming agent of the present invention, polyethylene oxide, carbomer, hydroxyethyl cellulose, methyl cellulose, xanthan gum, hypromellose, and the like may be used. Preferably, hypromellose having high viscosity and rigidity may be used. In this case, hypromellose having a viscosity of 100,000 cps may be used, but is not limited thereto. As hypromellose having a viscosity of 100,000 cps, hypromellose 2208 commercially supplied by Shin-Etsu Co., Ltd. (Japan) can be used.

The viscosity of the matrix forming agent of the present invention is preferably 4000 to 150000 cps. If the viscosity of the matrix forming agent is less than 4000 cps, the matrix system is destroyed due to the rapid expansion of the swelling agent and the movement of the gastrointestinal tract in the human body, and there is a danger that the drug release rate cannot be controlled. Excessive amount of swelling agent should be added and there is a problem in the oral dosage form in the excessive size, considering the weight of the additive is usually added to the formulation.

The matrix forming agent is preferably included 20 to 40% by weight relative to the total weight of the formulation according to the present invention. If the amount is less than 20% by weight, the swelling agent has a low resistance to swelling and movement of the gastrointestinal tract, and there is a risk of destroying the matrix system. If the amount is more than 40% by weight, the swelling speed is lowered, which makes it difficult to obtain the expected swelling effect. There is a problem that the addition of excessive swelling agent to achieve is produced in undesirable sizes in the above-mentioned oral dosage form.

The gas generating agent according to the present invention means a component having a function of generating a gas in the body to float the pharmaceutical preparation according to the present invention.

Since general gas generators react in an acidic environment to generate carbon dioxide, they are often used in combination with an acidifying agent. However, since the preparation according to the present invention is designed to prolong the residence time in the stomach, which is an acidic environment in consideration of absorption and release of pregabalin, it is preferable to use a gas generating agent capable of causing a reaction without an acidifying agent. As a gas generating agent, sodium carbonate, sodium bicarbonate, etc. were used, It is more preferable to use sodium bicarbonate.

The gas generating agent is preferably contained 1 to 20% by weight relative to the total weight of the formulation. If less than 1% by weight of the amount of gas generated is a problem that is difficult to float the formulation, if it exceeds 20% by weight oral administration there is a problem that the initial excessive gas is generated to destroy the matrix system.

The preparation according to the present invention may be suspended in an acidic solution of pH 1 to pH 4 within 60 minutes, and may be suspended for at least 5 hours and up to 24 hours, and thus sustained sustained release for a long time in the stomach.

In addition, since the preparation according to the present invention may increase from 1.5 to 2 times with respect to the total volume of the initial preparation within 1 hour in a solution of pH 1 to pH 4, gastric passage is prevented and sustained sustained release in the stomach for a long time Can be maintained.

The preparations according to the invention may further comprise excipients and excipients such as binders, lubricants and the like which increase hardness. As the binder, polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, and the like may be used, and the lubricant may include talc, stearyl fumarate, magnesium stearate, and the like, but is not limited thereto.

In addition, the pharmaceutical preparation according to the present invention can be coated as a material that can prevent moisture absorption after molding the tablets to ensure the stability of pregabalin, waxes, paraffins, phthalic acid derivatives, polyvinyl alcohol, cellulose acetate, hydroxide Roxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose and the like and a complex prescription thereof may be used.

Formulations of the present invention, based on pregabalin, can be administered to adults in a range of 150 to 600 mg total daily, and can be administered once daily.

In addition, the formulations of the present invention can be prepared in a variety of formulations, for example, can be formulated into tablets, powders, granules, capsules and the like, such as uncoated tablets, coated tablets, multi-layered tablets, or nucleated tablets.

The route of administration of the preparation of the present invention is not particularly limited but is preferably administered orally.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are merely to illustrate the present invention, the contents of the present invention is not limited to the following examples.

Tablet manufacturing method

Components except magnesium stearate were passed through a No. 35 sieve and then mixed for 15 minutes using a mixer (P-20087, Drum mixer,). The obtained mixture was prepared into granules using an oscillator (YBK-60, Zhangjiagang Create Mechanical Manufacturing) equipped with a No. 18 body after producing a slate using a compressor (MFL-01, Freund). Subsequently, magnesium stearate, which passed through No. 35 through granules, was added, and mixed at 14 rpm for 5 minutes in a mixer (P-20087, Drum mixer). This mixture was molded into tablets having a hardness of 15-20 kgf using a tablet press equipped with a rectangular punch of 19 mm long axis and 9 mm long axis.

Example 1  And Comparative Example 1 ~ 4

Example 1 was composed of a composition containing all of the matrix forming agent, swelling agent, gas generator, Comparative Examples 1 to 3 were excluded from one of the three functional materials, Comparative Example 4 was configured to exclude all three materials . The tablets prepared according to the tablet manufacturing method were observed for dissolution of the drug and physical properties of the preparation according to the presence of each substance. Table 1 shows the composition (mg / tablet) of Example 1 and Comparative Examples 1-4.

fair ingredient Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 compression Pregabalin 300 300 300 300 300 Hypromellose  2208 100000 300 - 300 300 - Sodium starch glycolate 40 40 - 40 - Sodium bicarbonate 80 80 80 - - Microcrystalline cellulose (remaining amount) 118 418 158 198 538 Hydroxypropylcellulose 155 155 155 155 155 Post-mix Magnesium stearate 7 7 7 7 7 Sum 1000 1000 1000 1000 1000

Example 2 , 3 and Comparative Example 5 To 8

Examples 2 and 3 and Comparative Examples 5 to 8 are compositions designed to determine the difference according to the amount and viscosity of hypromellose, which is a matrix forming agent. The manufacturing method was the same as above. Table 2 shows the compositions (mg / tablet) of Examples 2 and 3 and Comparative Examples 5 to 8.

fair ingredient Example 2 Example 3 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 compression Pregabalin 300 300 300 300 300 300 Hypromellose  2208 100000 200 350 150 400 Hypromellose  2208 4000 350 Hypromellose  2208 150000 200 Sodium starch glycolate 40 40 40 40 40 40 Sodium bicarbonate 80 80 80 80 80 80 Microcrystalline cellulose (remaining amount) 218 68 268 18 68 218 Hydroxypropylcellulose 155 155 155 155 155 155 Post-mix Magnesium stearate 7 7 7 7 7 7 Sum 1000 1000 1000 1000 1000 1000

Example 4 , 5 and Comparative Example 9 , 10

Examples 4, 5 and Comparative Examples 9, 10 are compositions designed to investigate the physical properties of the preparations according to the amount of sodium starch glycolate added as a swelling agent. The preparation method was the same as above. Table 3 shows the compositions (mg / tablet) of Examples 4 and 5 and Comparative Examples 9 and 10.

fair ingredient Example 4 Example 5 Comparative Example 9 Comparative Example 10 compression Pregabalin 300 300 300 300 Hypromellose 2208 100000 300 300 300 300 Sodium starch glycolate 20 80 10 100 Sodium bicarbonate 80 80 80 80 Microcrystalline cellulose (remaining amount) 138 78 148 58 Hydroxypropylcellulose 155 155 155 155 Post-mix Magnesium stearate 7 7 7 7 Sum 1000 1000 1000 1000

Example 6 , 7 and Comparative Example 11 , 12

Examples 6, 7 and Comparative Examples 11 and 12 are compositions designed to investigate the change in physical properties of the formulation according to the amount of the sodium bicarbonate which is a gas generator. The preparation method was the same as above. Table 4 shows the compositions (mg / tablet) of Examples 6 and 7 and Comparative Examples 11 and 12.

fair ingredient Example 6 Example 7 Comparative Example 11 Comparative Example 12 compression Pregabalin 300 300 300 300 Hypromellose 2208 100000 300 300 300 300 Sodium starch glycolate 40 40 40 40 Sodium bicarbonate 40 100 20 120 Microcrystalline cellulose (remaining amount) 158 98 178 78 Hydroxypropylcellulose 155 155 155 155 Post-mix Magnesium stearate 7 7 7 7 Sum 1000 1000 1000 1000

Experimental Example  1-Dissolution Rate Assessment

The dissolution test was performed in 900 mL of pH 1.2 solution according to Dissolution Test Method No. 1 (Basket Method) of the general test method of the Korean Pharmacopoeia. 3 mL was taken at 0.5, 1, 2, 4, 6, 8, 10, 16 and 24 hours, and 2 mL was passed through a 0.45 μm PVDF filter.

Detector: UV-visible spectrophotometer

Column: Capcell Pak-C18, 150 × 4.6 mm, particle size 5 μm or equivalent column

Column temperature: 30 ° C

Flow rate: 1.0 mL / min

Injection volume: 50 μl

Detector wavelength: 210 nm

Mobile phase: buffer / methanol / acetonitrile = 800/150/50 adjusted to pH 7.0 with phosphoric acid (buffer = 3.5 g K2HPO4 dissolved in 1000 mL purified water)

In Table 5, the dissolution rates of Example 1 and Comparative Examples 1 to 4 are shown, and the dissolution rates of Light Comparative Examples 2 and 3 of Example 1 are shown in FIG. 1. Table 5 shows the dissolution rate (%) of pregabalin over time (Example 1 and Comparative Examples 1 to 4).

Time (hr) Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 0 0 0 0 0 0 0.5 7.3 98.1 3.2 4.3 97.5 One 12.6 99.2 8.4 8.7 99.4 2 20.5 99.5 15.9 13.2 100.5 4 36.8 30.8 28.7 6 50.4 42.1 43.1 8 60.9 54.2 53.2 10 68.9 62.3 63.7 16 88.1 82.1 83.4 24 97.8 99.9 95.2

Referring to the experimental results, Comparative Example 1 and Comparative Example 4, in which hypromellose was not added as a matrix forming agent, had a rapid burst of drug due to dissolution of the initial dissolution tablet. The release rate of the drug with or without the addition of a swelling agent and a gas generating agent does not show a big difference, so it can be predicted that the additive controlling the release rate of the drug is hypromellose, which is a matrix forming agent.

In addition, the dissolution test results of Examples 2 and 3 and Comparative Examples 5 to 8 comparing the release rate of the drug according to the amount and viscosity of hypromellose are shown in Table 6. Table 6 shows the dissolution rate (%) of pregabalin over time (Examples 2 and 3 and Comparative Examples 5 to 8).

Time (hr) Example 2 Example 3 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 0 0 0 0 0 0 0 0.5 12.3 6.2 28.8 4.2 8.2 7.3 One 18.6 10.6 40.8 8.2 12.8 10.5 2 27.9 17.3 52.3 12.6 20.5 17.6 4 43.2 33.8 67.9 24.2 38.7 34.5 6 56.8 47.2 77.8 35.4 53.4 46.2 8 67.5 57.8 86.4 45.6 62.3 58.1 10 76.4 65.7 93.8 55.3 70.5 66.2 16 93.4 85.4 98.7 74.3 90.5 87.5 24 97.5 95.8 99.4 87.5 99.2 98.4

At the same viscosity, the release rate of the drug tended to increase as the addition amount decreased, and the dissolution rate tended to decrease as the viscosity increased.

Experimental Example  2-swelling rating

The swelling degree of Examples 4 and 5 and Comparative Examples 9 and 10 were measured to compare the degree of swelling according to the inclusion of swelling agent and gas generator in the tablet containing 30% of hypromellose 2208. The tablets were put into the basket at the outlet of 900 mL of the pH 1.2 solution and stirred at a rotating speed of 50 rpm and the size of the tablets with time was measured using a vernier caliper (CD-20CPX, Mitutoyo Corp.). The results are shown in Table 7. Table 7 shows the results of the tablet size evaluation (Examples 4, 5 and Comparative Examples 9, 10) over time.

Example 4 Example 5 time
(hr) Long axis
(mm) shorten
(mm) Height
(mm) volume
(mm ³ ) Long axis
(mm) shorten
(mm) Height
(mm) volume
(mm ³ ) 0 19.2 9.2 6.9 1216.1 19.2 9.2 6.9 1213.3 0.5 19.9 10.9 8.1 1756.1 21.3 12.7 9.1 2457.4 One 20.2 13.6 9.1 2514.1 22.5 14.7 10.1 3333.2 2 20.6 14.5 10.3 3083.8 23.0 16.2 11.5 4263.3 Comparative Example 9 Comparative Example 10 time
(hr) Long axis
(mm) shorten
(mm) Height
(mm) volume
(mm ³ ) Long axis
(mm) shorten
(mm) Height
(mm) volume
(mm ³ ) 0 19.2 9.3 6.8 1211.1 19.1 9.2 6.8 1203.7 0.5 19.4 9.3 7.0 1263.3 Tablet destroyed One 19.9 9.5 7.1 1349.7 2 20.0 9.7 7.3 1405.9

Referring to Table 7, the swelling speed of the tablets increased as the amount of swelling agent was increased, and Comparative Example 10, in which the amount of the swelling agent was added at 10% of the total weight, did not maintain the matrix system due to the excessive amount of swelling agent due to the disintegration of the initial tablets in the test. I could not see. In addition, in the case of Comparative Example 9 in which the amount of the swelling agent was 1% by weight, the length of the short axis was less than 10 mm by 2 hours, and thus, there was a fear of passing through the pylorus during the oral administration.

Experimental Example  3-float time evaluation

To evaluate the suspension time of the designed tablets, tablets were dropped into an eluent containing 900 mL of pH 1.2 solution and pH 4.0 solution (Korean Pharmacopoeia), each warmed at 37 degrees, and the time for which the tablets were suspended was measured. The results are shown in Table 8. Table 8 shows the measurement results of the suspension time of the tablet containing the gas generator.

Specimen Suspension time (minutes) in pH 1.2 liquid Suspension time (min) in pH 4.0 solution Example 6 10-12 15-18 Example 7 3 to 5 7 to 10 Comparative Example 3 180-200 180-200 Comparative Example 11 60 to 70 80 ~ 90 Comparative Example 12 Tablet destruction within 5 minutes Tablet destruction in 5-8 minutes

Referring to Table 8, the tablet of Comparative Example 3, in which sodium bicarbonate was not added, was slowly suspended after about 180 minutes, and the addition time showed a tendency to increase the suspension time. Examples 6 and 7 showed desirable results with a suspension time of about 20 minutes. However, in Comparative Example 12, which contained 12% of the total weight of sodium bicarbonate, the tablets were broken between about 5-8 minutes after the tablet dropping, and thus the matrix system was not maintained.

Experimental Example  4-Gastrointestinal Movement Resistance Prediction

In order to predict the resistance in the gastrointestinal tract to the tablets of Example 1, tablets placed in the sinker according to the Elution Test Method 2 (paddle method) of the Korean Pharmacopoeia General Test Method were prepared using 900 mL of pH 1.2 solution as the test solution. The dissolution test was carried out at 50 rpm and 100 rpm, respectively. Quantification of the drug was analyzed in the same manner as in Experiment 1. The results are shown in Table 9. Table 9 shows the dissolution rate comparison results of Example 1 according to the stirring speed.

Time (hr) 50 rpm 100 rpm 0 0 0 0.5 7.3 13.2 One 12.6 18.3 2 20.5 26.8 4 36.8 41.6 6 50.4 54.8 8 60.9 66.2 10 68.9 75.3 16 88.1 93.5 24 97.8 99.1

Referring to Table 9, the dissolution rate according to the rotational speed was within about 6%, and it was predicted that the rapid release of the drug was unlikely due to the movement of the gastrointestinal tract.

Experimental Example  5-stability evaluation

In order to evaluate the stability of the tablets prepared according to the composition of Example 1, samples were placed in HDPE bottles and stored at 40 ° C and 75% relative humidity. The change in content was observed.

The experimental results are shown in Table 10 below. Table 10 shows the stability evaluation results of Example 1.

time content(%) Lactam content (%) Start 99.6 0 2 weeks 99.4 0.03 4 weeks 99.5 0.02 6 weeks 99.4 0.03 3 months 98.8 0.05 6 months 98.4 0.07

Referring to Table 10, the change in content up to 6 months was negligible and the main degradation product lactam also showed a value of less than 0.1%, the formulation of Example 1 was found to be stable.

Experimental Example  Pharmacokinetic Evaluation in 6-Animals

To evaluate the bioavailability and pharmacokinetic parameters of the test drug containing 300 mg of pregabalin, a test was conducted using beagle dogs using commercially available Lyrica capsule (pregabalin 150 mg) as a control agent in Pfizer. Test drug was prepared and used in the same composition as in Example 1. 12 healthy beagle dogs (9.45 ~ 12.60Kg, 28 ~ 29 months old) were divided into 2 groups of 6 dogs each, and in the first group, control capsules twice a day, 1 capsule (150 mg each as pregabalin) 12 The group was orally administered at intervals of time, and the second group was orally administered test tablets once a day and once tablets (300 mg as pregabalin). After oral administration, the control and test drug administration groups were collected for 48 hours, and the concentration of pregabalin in plasma was quantitatively analyzed by LC-MS / MS. Based on the results, pharmacokinetic parameters such as Cmax, Tmax, AUCt, T1 / 2, Vd / F and CL / F of the control and test preparations were calculated.

The experimental results are shown in FIG. 2 and Table 11. In FIG. 2 and Table 11, Reference is a demonstration result in the first group of the control formulation, and Test represents an experimental result in the second group of the sustained release test formulation. Table 11 shows the pharmacokinetic parameters after oral administration of pregabalin formulations in beagle dogs.

Referring to FIG. 2 and Table 11, in the case of pregabalin in plasma, the sustained release test preparation showed a relative bioavailability of about 70-73% of the immediate release control preparation, and tmax and t1 / 2 were immediate release control preparations. It showed that the characteristic as a sustained release formulation was shown by showing the longer result.

Claims (7)

A sustained release formulation comprising pregabalin or a pharmaceutically acceptable salt thereof as an active ingredient, the sustained release formulation further comprising at least one of a swelling agent, a matrix former, and a gas generating agent.
The method according to claim 1,
Sustained release preparation, characterized in that the matrix forming agent is hypromellose.
The method according to claim 1,
Sustained release formulation, characterized in that the viscosity of the matrix forming agent is 4000 to 150000 cps.
The method according to claim 1 or 2,
The swelling agent is sodium starch glycolate, the gas-generating agent is sustained-release preparation, characterized in that sodium bicarbonate.
The method according to claim 1,
Sustained release preparation, characterized in that the swelling agent 2 to 8% by weight, the matrix forming agent 20 to 35% by weight, the gas generator is 4 to 10% by weight based on the total weight of the sustained release formulation.
The method according to claim 3,
The sustained-release preparation is suspended in a solution of pH 1.2 to pH 4.0 within 30 minutes, sustained-release preparation, characterized in that the suspension is maintained for 5 hours to 24 hours.
The method according to claim 3,
The sustained release formulation is characterized in that the sustained release formulation increases by 1.5 to 2 times the total volume of the initial sustained release formulation in a solution of pH 1.2 to pH 4.0 within 1 hour.

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