JPH0460090B2 - - Google Patents

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Publication number
JPH0460090B2
JPH0460090B2 JP57234521A JP23452182A JPH0460090B2 JP H0460090 B2 JPH0460090 B2 JP H0460090B2 JP 57234521 A JP57234521 A JP 57234521A JP 23452182 A JP23452182 A JP 23452182A JP H0460090 B2 JPH0460090 B2 JP H0460090B2
Authority
JP
Japan
Prior art keywords
long
surfactant
lipid
drug
acting
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP57234521A
Other languages
Japanese (ja)
Other versions
JPS59122425A (en
Inventor
Kyoji Koyari
Suehiro Matsuda
Akira Ito
Masayuki Hasegawa
Shinichi Kimura
Takao Goto
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kaken Pharmaceutical Co Ltd
Original Assignee
Kaken Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kaken Pharmaceutical Co Ltd filed Critical Kaken Pharmaceutical Co Ltd
Priority to JP23452182A priority Critical patent/JPS59122425A/en
Publication of JPS59122425A publication Critical patent/JPS59122425A/en
Publication of JPH0460090B2 publication Critical patent/JPH0460090B2/ja
Granted legal-status Critical Current

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Description

【発明の詳細な説明】[Detailed description of the invention]

本発明は持続性製剤およびその製造法に関す
る。 持続性製剤、とくに持続性の医薬品は投与回数
を減らす、すなわち効力を持続させる目的、また
必要以上に血中濃度を上げない、すなわち副作用
を軽減する目的から種々の検討がなされてきた。
しかしながら、従来より行なわれているいゆるコ
ーテイング法、湿式造粒法、熔融造粒法などで
は、放出特性においロツト間、ロツト内のバラツ
キが大きく、また技術的にみても満足しうるもの
ではなかつた。たとえば、コーテイング法につい
てはフイルムの厚さ(量)を全ての顆粒または錠
剤に均一でしかもピンホールなどに施すことは不
可能であり、湿式造粒法については造粒物の一粒
子からみれば不均一で医薬の放出をコントロール
するところまでいたらなかつた。また熔融造粒法
についてはわずかな脂質の量の違いで放出量が異
なつたり、錠剤の大きさ、圧力、硬度によつても
放出量にかなり影響を受けていた。 叙上の持続性製剤の欠点を解決するため、種々
の検討がなされており、たとえば特開昭57−
34854号公報に記載の徐放性粉体の製造法がある。 しかしながら、前記方法は、あくまで被覆重合
体中に医薬と溶出調節剤を含有するいわゆる広義
のコーテイング法である。そのため被覆重合体が
溶出の際に体内に残るという欠点があり、また重
合体中に医薬を溶解させる際あるいは被覆された
医薬を分離する際に種々の有機溶媒を用いるた
め、該有機溶媒による大気汚染、体内残留の危険
性などの種々の欠点がみられる。 かかる現状に鑑み、本発明者らは被覆重合体を
用いずに溶出調節剤の脂質を加温溶融させたもの
を媒体として用い、さらにいまひとつの溶出調節
剤として界面活性剤を加えることによつて、被覆
重合体を用いなくても医薬の溶出が確実に制御さ
れ、しかも人体に有害な溶媒を使用することなく
加温熔融という接作のみで簡単でかつ経済的に持
続性製剤を製造しうることを見出し、本発明を完
成するにいたつた。 すなわち、本発明は脂質の中に医薬および界面
活性剤が均一に熔融および(または)分散されて
いることを特徴とする持続性製剤およびその製造
法に関する。 本発明の脂質とは製剤上許容しうる水不溶性物
質で、医薬の溶出を遅らせる作用を有し、好まし
い軟化点または融点(40〜150℃)を有する物質
のことであり、硬化油またはパラフイン、さらに
詳しくは、カルナバロウ、合成および天然パラフ
イン、密ロウ、鯨ロウ、カスターワツクス、牛
脂、水素添加植物油(たとえばラブリーワツクス
101(フロイント産業(株)製)、ラブリーワツクス102
(フロイント産業(株)製))、脂肪アルコール、ステ
アリン酸などの脂肪酸、脂肪酸の塩、グリセライ
ドなどがあげられる。 前記脂質を加温熔融させ、該脂質中に医薬およ
びアビセル、スターチ、アエロジルなどの賦形剤
の微粒子を適量加えて均一に熔融および(また
は)分散させることによつても持続性製剤をうる
ことができるが、通常、脂質のみで溶出を調節し
ようとすると、脂質量のわずかな違いまたは操作
の違いにより溶出率、血中濃度等のバラツキが大
きく再現性が乏しい。このことは、たとえば医薬
として消炎鎮痛剤のフルルビプロフエン(以下、
FPという)、脂質として硬化油を用いて仮に3時
間値の薬物溶出率を50%に制御するばあいについ
て調べ結果を示す第1図または第1表から明らか
である。ただし溶出試験は第9改正日本薬局方
(以下、9局という)崩壊試験法に準じた。
TECHNICAL FIELD The present invention relates to depot formulations and methods for their production. Various studies have been conducted on long-acting preparations, especially long-acting drugs, with the aim of reducing the number of administrations, that is, sustaining the efficacy, and also for the purpose of not increasing the blood concentration more than necessary, that is, reducing side effects.
However, the conventional coating methods, wet granulation methods, melt granulation methods, etc. have large variations in release characteristics between and within lots, and are not satisfactory from a technical standpoint. . For example, with the coating method, it is impossible to uniformly apply the film thickness (amount) to all granules or tablets and even pinholes, and with the wet granulation method, it is impossible to apply the film thickness (amount) uniformly to all granules or tablets, and with the wet granulation method, It was not possible to control the release of the drug due to non-uniformity. Furthermore, with the melt granulation method, the amount released varies depending on the slight difference in the amount of lipid, and the amount released is also significantly affected by the size, pressure, and hardness of the tablet. In order to solve the above-mentioned shortcomings of long-acting preparations, various studies have been made, for example,
There is a method for producing sustained release powder described in Japanese Patent No. 34854. However, the above method is a so-called coating method in a broad sense, in which the coating polymer contains a drug and an elution modifier. Therefore, there is a drawback that the coated polymer remains in the body during elution, and since various organic solvents are used when dissolving the drug in the polymer or separating the coated drug, the organic solvent may cause atmospheric pressure. There are various drawbacks, such as the risk of contamination and persistence in the body. In view of this current situation, the present inventors did not use a coating polymer, but instead used a heated melted lipid as an elution modifier as a medium, and further added a surfactant as another elution modifier. , drug elution can be reliably controlled without the use of a coating polymer, and long-lasting preparations can be easily and economically produced simply by heating and melting without using solvents that are harmful to the human body. This discovery led to the completion of the present invention. That is, the present invention relates to a long-acting preparation characterized by having a drug and a surfactant uniformly melted and/or dispersed in a lipid, and a method for producing the same. The lipid of the present invention is a water-insoluble substance that is acceptable for formulation, has the effect of delaying the elution of medicine, and has a preferable softening point or melting point (40 to 150°C), such as hydrogenated oil or paraffin, More specifically, carnauba wax, synthetic and natural paraffins, beeswax, spermaceti, castor wax, beef tallow, hydrogenated vegetable oils (such as lovely wax)
101 (manufactured by Freund Sangyo Co., Ltd.), Lovely Wax 102
(manufactured by Freund Sangyo Co., Ltd.), fatty alcohols, fatty acids such as stearic acid, fatty acid salts, and glycerides. A long-lasting preparation can also be obtained by heating and melting the lipid, adding an appropriate amount of fine particles of the drug and excipient such as Avicel, starch, Aerosil, etc. to the lipid and uniformly melting and/or dispersing the mixture. However, when attempting to control elution using only lipids, the elution rate, blood concentration, etc. vary widely due to slight differences in the amount of lipids or differences in operation, resulting in poor reproducibility. This means, for example, that the anti-inflammatory analgesic flurbiprofen (hereinafter referred to as
This is clear from FIG. 1 or Table 1 showing the results of a study in which the 3-hour drug dissolution rate was controlled to 50% using hydrogenated oil as the lipid (referred to as FP). However, the dissolution test was based on the 9th revised Japanese Pharmacopoeia (hereinafter referred to as 9th Pharmacopoeia) disintegration test method.

【表】 すなわち、医薬量に対して9%(重量%、以下
同様)の硬化油を用いることにより医薬の溶出を
制御できるようになるが、12%では溶出率が38
%、8%では溶出率が60%になつたりして、わず
かな脂質量の違いにより溶出率のバラツキが大き
いことが明らかである。 そこで、いまひとつの溶出調節剤の界面活性剤
を加えたところ、これが溶出を速める制御因子と
なり医薬の溶出を確実に制御しえた。たとえば第
1図に示すように医薬量に対し20%以上の硬化油
を用いて多少の硬化油量の差が溶出率へほぼ影響
を与えないようにしたのち、界面活性剤を加える
ことにより溶出率を自由に制御しえた。つまり、
第1図に示す非直線部分でのみ制御せずに勾配の
少ない直線部分を利用してそのレベルを界面活性
剤で制御するわけである。 本発明の界面活性剤とは医薬に用いたばあい生
体に有害でないもの、たとえばシヨ糖脂肪酸エス
テル、ツイン8、ラウリル硫酸ナトリウム、
PEG#6000などがあげられる。 また本発明の持続性製剤は叙上のごとく薬物を
脂質の中に均一に熔融および(または)分散せし
めたものであるため、水溶性医薬、たとえば塩酸
ベフノロール(以下、BFという)、塩酸イソプロ
テノール、塩酸エタンブトール、塩酸ブプラノロ
ールなどはもちろんのこと、難溶性医薬、たとえ
ばFP、イブプロフエン(以下、IPという)、リフ
アンピシン、アモキシシリン、テガフル、フルオ
ロウラシル、インドメタシン、ニフエジピンなど
も9局液中でコアの外周から徐々に溶解せしめ
ることができ、しかも被覆重合体を用いいないた
め通常の持続性製剤を溶出させる際にみられる外
皮残る、顆粒状になつた粒子が溶出後も残るなど
の欠点を有さない。 なお、該持続性製剤は造粒物のままでも持続効
果を有するが、ヒトへの服用という観点からはカ
プセル剤または錠剤とするのが好ましい。 本発明の持続性製剤を製造するには、加温でき
る容器中に脂質を適量、医薬量に対し1/40〜40
倍、好ましくは1/25〜20倍を投入し、40〜150℃
で加温熔融させ、該脂質中に医薬および医薬量に
対し0.01〜2.0倍、好ましくは0.02〜1.0倍の界面
活性剤を加え、さらに必要に応じて賦形剤、滑沢
剤を加えて均一に熔融および(または)分散させ
たのち、スプレークーラー法により目的とする粒
度に噴霧冷却するか、あるいは一度冷却固化させ
たのち目的とする粒度にする。 叙上のごとく本発明の方法においては脂質の軟
化点または融点を利用し、加温熔融した脂質の中
に医薬を均一に熔融および(または)分散させる
方法を用いるため、FP、IP、インドメタシン、
ニフエジピン、リフアンピジン、アモキシシリ
ン、テガフル、フルオロウラシルなどの融点が
100℃以上の難溶性医薬を医薬自身の融点よりも
低い温度で溶かすことができ、医薬の安定性の面
からも好ましい。また水溶性医薬に関しては融点
以上に加温してもよいが、安定性と安全性の面か
らみても好ましくないため、たとえば100メツシ
ユあるいはそれ以上の細かい粒子に粉砕してから
熔融した脂質に均一に分散させるのが好ましい。 叙上のごとく本発明の方法は、有機溶媒を一切
用いていないため、製造過程において大気汚染を
生じることがなく、えられる製剤自身にも残留有
機溶媒の危険性が全くなく、また、溶媒を蒸発さ
せるための乾燥装置も不要であり、工程非常に簡
単であるため特別な注意事項をもつた作業標準、
特別な装置なども不要であり、単純で経済的な方
法である。 本発明はまた脂質の中に医薬および界面活性剤
が均一に熔融および(または)分散されてなる徐
放部と通常の医薬で構成された易溶部とからなる
持続性製剤に関する。 すなわち、叙上の持続性製剤からなる徐放部に
易溶部を追加することにより、速かに有効血中濃
度に到達せしめたのち、代謝されていく量を徐放
部で補う持続性製剤で、徐放部と易溶部の比率を
変えることにより有効血中濃度を自由に制御しう
るものであり、速効性と持続性の両方が要求され
る薬物に好適である。たとえば、β−ブロツカー
のBF、塩酸ブプラノロールなどは速効性が要求
され、予防製剤としても重要なものであるが、と
くに昼間の投与のわずらわしさをなくすためには
持続性製剤にする必要がある。さらに該医薬は心
臓病薬として用いる場合には医薬放出のバラツキ
が生じては目的を達しえないが、本発明の持続性
製剤によれば医薬の放出はバラツキなく一定であ
る。 なお、該持続性製剤は錠剤たとえば二層錠(第
2a図)、三層錠(第2b図)または有核錠(第
2c図)(だし第2a〜2c図中の1は徐放部、
2は易溶部である)もしくはカプセル剤として用
いる。 一般に持続性製剤において、とくに錠剤とする
ばあいには、いくら精度よく重量調整をしたり、
打錠圧を調整しても、厚さのバラツキや硬度のバ
ラツキが生じてくるため、溶出量にバラツキを生
ぜしめないようにすることは困難である。それに
対し、本発明の持続性製剤は錠剤とする際に打錠
圧、硬度、大きさなどの影響が少なく、工程も極
めて単純でありながら溶出量を自在に制御するこ
とができる。 つぎに実施例をあげて本発明をさらに詳しく説
明する、本発明はかかる実施例のみに限定される
ものではない。 なお、実施例中の溶出率は9局の崩壊試験に準
じて行なつた溶出試験により求め、溶出液として
は9局の液もしくは液を用いた。 実施例 1
[Table] In other words, the elution of the drug can be controlled by using 9% (wt%) hydrogenated oil based on the amount of the drug, but at 12%, the elution rate is 38%.
% and 8%, the elution rate reaches 60%, and it is clear that the elution rate varies greatly due to slight differences in the amount of lipid. Therefore, when we added a surfactant, another elution regulator, this became a control factor that accelerated the elution, and we were able to reliably control the elution of the drug. For example, as shown in Figure 1, after using a hydrogenated oil that accounts for 20% or more of the amount of the drug so that slight differences in the amount of hydrogenated oil have almost no effect on the dissolution rate, the elution can be achieved by adding a surfactant. The rate could be controlled freely. In other words,
Rather than controlling only the non-linear portion shown in FIG. 1, the level is controlled using the surfactant by utilizing the linear portion with a small slope. The surfactant of the present invention is one that is not harmful to living organisms when used in medicine, such as sucrose fatty acid ester, Twin 8, sodium lauryl sulfate,
Examples include PEG#6000. In addition, since the long-acting preparation of the present invention has a drug uniformly melted and/or dispersed in lipids as described above, water-soluble drugs such as befunolol hydrochloride (hereinafter referred to as BF), isoprotenol hydrochloride, etc. , ethambutol hydrochloride, bupranolol hydrochloride, etc., as well as poorly soluble drugs such as FP, ibuprofen (hereinafter referred to as IP), rifampicin, amoxicillin, tegaflu, fluorouracil, indomethacin, and nifedipine, etc., are gradually absorbed from the outer periphery of the core in the 9 topical fluids. Furthermore, since no coating polymer is used, it does not have the disadvantages that occur when dissolving conventional long-acting preparations, such as leaving behind a shell or leaving granular particles after dissolution. Although the long-acting preparation has a long-lasting effect even in the form of granules, it is preferably in the form of capsules or tablets from the viewpoint of human administration. To produce the long-acting preparation of the present invention, add an appropriate amount of lipid in a heatable container to 1/40 to 40 of the pharmaceutical amount.
Pour 1/25 to 20 times, preferably 1/25 to 20 times, and heat to 40 to 150℃.
0.01 to 2.0 times, preferably 0.02 to 1.0 times the amount of the drug and surfactant relative to the amount of the drug is added to the lipid, and if necessary, excipients and lubricants are added to homogenize. After being melted and/or dispersed, the particles are spray-cooled to the desired particle size using a spray cooler method, or once cooled and solidified, the desired particle size is obtained. As mentioned above, in the method of the present invention, the softening point or melting point of the lipid is used to uniformly melt and/or disperse the medicine in the heated and melted lipid, so FP, IP, indomethacin,
The melting point of nifedipine, rifampidine, amoxicillin, tegaflu, fluorouracil, etc.
It is possible to melt a poorly soluble drug at a temperature of 100°C or higher at a temperature lower than the melting point of the drug itself, which is preferable from the viewpoint of drug stability. In addition, water-soluble drugs may be heated above their melting point, but this is not preferable from the standpoint of stability and safety. It is preferable to disperse it. As mentioned above, the method of the present invention does not use any organic solvent, so there is no air pollution during the manufacturing process, and the resulting preparation itself has no danger of residual organic solvent. There is no need for drying equipment for evaporation, and the process is very simple, so the work standard has special precautions.
It is a simple and economical method that does not require any special equipment. The present invention also relates to a sustained-release preparation consisting of a sustained-release region in which a drug and a surfactant are uniformly melted and/or dispersed in a lipid, and an easily soluble region composed of a conventional drug. In other words, by adding an easily soluble part to the sustained-release part of the above-mentioned sustained-release preparation, the effective blood concentration is quickly reached, and then the sustained-release part supplements the amount that is metabolized. The effective blood concentration can be freely controlled by changing the ratio of the sustained release part to the easily soluble part, and it is suitable for drugs that require both immediate action and long-lasting effect. For example, β-blockers such as BF and bupranool hydrochloride are required to be fast-acting and are important as preventive preparations, but they need to be made into long-acting preparations in order to avoid the hassle of daytime administration. Furthermore, when the drug is used as a heart disease drug, the purpose cannot be achieved if there is variation in drug release, but according to the sustained-release preparation of the present invention, drug release is constant without variation. Note that the long-acting preparation is a tablet such as a two-layer tablet (Fig. 2a), a three-layer tablet (Fig. 2b), or a dry-coated tablet (Fig. 2c) (1 in Fig. 2a to 2c is a sustained release part,
2 is an easily soluble part) or used as a capsule. In general, when it comes to long-acting preparations, especially when they are made into tablets, it is important to adjust the weight accurately.
Even if the tableting pressure is adjusted, variations in thickness and hardness will occur, so it is difficult to prevent variations in the amount of elution. On the other hand, the long-acting preparation of the present invention is less affected by the tableting pressure, hardness, size, etc. when it is made into tablets, and the process is extremely simple, yet the dissolution amount can be freely controlled. Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples. In addition, the dissolution rate in the examples was determined by a dissolution test conducted according to the disintegration test of 9 stations, and the solution or solution of 9 stations was used as the eluent. Example 1

【表】 叙上の成分を用いてつぎに示す方法にしたがつ
て持続性製剤を製造した。 すなわち、ラブリーワツクス101を約90℃で熔
融させ、ついでFPおよびPEG#6000を加えて均
一に熔融せしめ、さらにアビセルを加えて充分混
合した。冷却固化後、粉砕して12メツシユ以下に
篩過し、さらにステアリン酸カルシウムを加え均
一に混合したのち、8.5mmφの杵で打錠し、えら
れた3種類の錠剤からの薬物の溶出率を調べ。結
果を第2表および第3図に示す。
[Table] A long-acting preparation was manufactured using the above ingredients and according to the method shown below. That is, Lovely Wax 101 was melted at about 90°C, then FP and PEG #6000 were added and melted uniformly, and Avicel was added and thoroughly mixed. After cooling and solidifying, the mixture was pulverized and sieved to a size of 12 mesh or less, and calcium stearate was added and mixed uniformly. The mixture was then compressed into tablets using an 8.5 mm diameter punch. The dissolution rate of the drug from the three types of tablets obtained was examined. . The results are shown in Table 2 and Figure 3.

【表】 第2表および第3表から明らかなように、溶出
調節剤のPEG#6000の量により目標とする溶出
率の3時間値が界面活性剤(対FP比10、20、30
%と増すこと)により約10%ずつ溶出量が増えて
いくことが判つた。また溶出試験においては錠剤
が外側から順に徐々に溶け出し、溶出が終了した
時点では全てが完全に溶解しているのが観察され
た。 実施例 2
[Table] As is clear from Tables 2 and 3, the target 3-hour value of elution rate depends on the amount of PEG#6000 as the elution regulator.
It was found that the amount of elution increases by approximately 10% as the amount increases by approximately 10%. In addition, in the dissolution test, it was observed that the tablet gradually began to dissolve from the outside, and by the time the dissolution was completed, all the tablets had completely dissolved. Example 2

【表】【table】

【表】 ム

[Table] Mu

Claims (1)

【特許請求の範囲】 1 脂質の中に医薬および界面活性剤が均一に熔
融および(または)分散されてなることを特徴と
する持続性製剤。 2 前記脂質が硬化油またはパラフインである特
許請求の範囲第1項記載の持続性製剤。 3 前記界面活性剤がシヨ糖脂肪酸エステル、ツ
イン80またはラウリル硫酸ナトリウムである特許
請求の範囲第1項または第2項記載の持続性製
剤。 4 前記特続性製剤の剤形がカプセル剤または錠
剤である特許請求の範囲第1項、第2項または第
3項記載の持続性製剤。 5 脂質を加温熔融したものに医薬および界面活
性剤を均一に熔融および(または)分散させるこ
とを特徴とする持続性製剤の製造法。 6 40〜150℃の温度で行なう特許請求の範囲第
5項記載の製造法。 7 前記脂質が硬化油またはパラフインである特
許請求の範囲第5項または第6項記載の製造法。 8 前記界面活性剤がシヨ糖脂肪族エステル、ツ
イン80またはラウリル硫酸ナトリウムである特許
請求の範囲第5項、第6項または第7項記載の製
造法。 9 脂質の中に医薬および界面活性剤が均一に熔
融および(または)分散されてなる徐放部と通常
の医薬で構成された易溶部とからなる持続性製
剤。 10 前記脂質が硬化油またはパラフインである
特許請求の範囲第9項記載の持続性製剤。 11 前記界面活性剤がシヨ糖脂肪酸エステル、
ツイン80またはラウリル硫酸ナトリウムである特
許請求の範囲第9項または第10項記載の持続性
製剤。 12 前記持続性製剤の剤形がカプセル剤または
錠剤である特許請求の範囲第9項、第10項また
は第11項記載の持続性製剤。 13 前記錠剤が二層錠、三層錠または有核錠で
ある特許請求の範囲第9項、第10項、第11項
または第12項記載の持続性製剤。
[Scope of Claims] 1. A long-lasting preparation characterized by having a drug and a surfactant uniformly melted and/or dispersed in lipid. 2. The long-acting preparation according to claim 1, wherein the lipid is hydrogenated oil or paraffin. 3. The long-acting preparation according to claim 1 or 2, wherein the surfactant is sucrose fatty acid ester, Twin 80, or sodium lauryl sulfate. 4. The long-acting preparation according to claim 1, 2, or 3, wherein the dosage form of the specific-release preparation is a capsule or a tablet. 5. A method for producing a long-acting preparation, which comprises uniformly melting and/or dispersing a drug and a surfactant in a heated and melted lipid. 6. The manufacturing method according to claim 5, which is carried out at a temperature of 40 to 150°C. 7. The manufacturing method according to claim 5 or 6, wherein the lipid is hydrogenated oil or paraffin. 8. The manufacturing method according to claim 5, 6, or 7, wherein the surfactant is sucrose aliphatic ester, Twin 80, or sodium lauryl sulfate. 9. A sustained-release preparation consisting of a sustained-release part in which a medicine and a surfactant are uniformly melted and/or dispersed in lipids and an easily soluble part made up of a conventional medicine. 10. The long-acting preparation according to claim 9, wherein the lipid is hydrogenated oil or paraffin. 11 The surfactant is a sucrose fatty acid ester,
11. The long-acting preparation according to claim 9 or 10, which is Twin 80 or sodium lauryl sulfate. 12. The long-acting preparation according to claim 9, 10, or 11, wherein the dosage form of the long-acting preparation is a capsule or a tablet. 13. The long-acting preparation according to claim 9, 10, 11, or 12, wherein the tablet is a double-layer tablet, a triple-layer tablet, or a dry-coated tablet.
JP23452182A 1982-12-27 1982-12-27 Sustained release preparation and its preparation Granted JPS59122425A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP23452182A JPS59122425A (en) 1982-12-27 1982-12-27 Sustained release preparation and its preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP23452182A JPS59122425A (en) 1982-12-27 1982-12-27 Sustained release preparation and its preparation

Publications (2)

Publication Number Publication Date
JPS59122425A JPS59122425A (en) 1984-07-14
JPH0460090B2 true JPH0460090B2 (en) 1992-09-25

Family

ID=16972323

Family Applications (1)

Application Number Title Priority Date Filing Date
JP23452182A Granted JPS59122425A (en) 1982-12-27 1982-12-27 Sustained release preparation and its preparation

Country Status (1)

Country Link
JP (1) JPS59122425A (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3437599C2 (en) * 1984-10-13 1987-04-16 Dolorgiet GmbH & Co KG, 5205 St Augustin Soft gelatin capsules containing ibuprofen
GB8524421D0 (en) * 1985-10-03 1985-11-06 Boots Co Plc Therapeutic agents
CH669523A5 (en) * 1986-06-25 1989-03-31 Mepha Ag
EP0956858B1 (en) * 1998-04-30 2001-10-31 Renata Maria Anna Cavaliere Vesely Pharmaceutical compositions containing Lactobacillus brevis and Lactobacillus salivarius for treatment of vaginal infections
EP2422772A3 (en) 2002-09-20 2012-04-18 Alpharma, Inc. Sequestering subunit and related compositions and methods
FR2848855B1 (en) * 2002-12-23 2005-02-11 Aventis Pharma Sa COMPOSITIONS FOR ORAL ADMINISTRATION OF ACTIVE INGREDIENTS REQUIRING TASTE MASKING

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF PHARMACEUTICAL SCIENCES=1966 *
JOURNAL OF PHARMACEUTICAL SCIENCES=1968 *

Also Published As

Publication number Publication date
JPS59122425A (en) 1984-07-14

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