GB2061111A - Long acting pharmaceutical composition - Google Patents
Long acting pharmaceutical composition Download PDFInfo
- Publication number
- GB2061111A GB2061111A GB8034222A GB8034222A GB2061111A GB 2061111 A GB2061111 A GB 2061111A GB 8034222 A GB8034222 A GB 8034222A GB 8034222 A GB8034222 A GB 8034222A GB 2061111 A GB2061111 A GB 2061111A
- Authority
- GB
- United Kingdom
- Prior art keywords
- tiaramide
- acceptable salt
- pharmaceutically acceptable
- composition
- pharmaceutical composition
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A long acting pharmaceutical composition comprises Tiaramide or its pharmaceutically acceptable salt, as an active ingredient, and a dissolution regulating agent. The composition may be covered with a readily soluble composition of Tiaramide or its pharmaceutically acceptable salt.
Description
SPECIFICATION
Long acting pharmaceutical composition
This invention relates to a long acting pharmaceutical composition of Tiaramide or its pharmaceutically acceptable salt.
More particularly, this invention reiates to a long acting pharmaceutical composition which comprises
Tiaramide or its pharmaceutically acceptable salt as an active ingredient and a dissolution regulating agent, wherein the said composition may be optionally covered with a readily soluble composition of
Tiaramide or its pharmaceutically acceptable salt.
Tiaramide, i.e. 3 -L4- (2 - hydroxyethyl - 1 - piperazinyl) - carbonylmethylj - 5 - chloro - 2 - benzothiazolinone or its pharmaceutically acceptable salt as used as an active ingredient in this invention is widely known as an excellent analgesic, antiallergic and antiinflammatory medicine, among which, Tiaramide hydrochloride is marketted in a form oftabletfororal administration use.
As to Tiaramide or its pharmaceutically acceptable salt, it is understood that said drug is very rapidly absorbed in the body, for example, its serum concentration in human beings comes up to the maximum within about one hour after its oral administration.
However, Tiaramide or its pharmaceutically acceptable salt is excreted so rapidly that more than 90% of Tiaramide is excreted in the urine within about 20 hours after its administration, and accordingly its serum concentration decreases rapidly in a short time after its administration.
Due to the behavior of Tiaramide or its pharmaceutically acceptable salt as explained above, it is necessary for patients to take the drug many times a day for efficient therapy.
After extensive studies of various pharmaceutical compositions, the problem as given above has been solved based upon the new finding that the inventors of this invention have found out a long acting pharmaceutical composition of Tiaramide or its pharmaceutically acceptable salt which comprises
Tiaramide or its pharmaceutically acceptable salt as an active ingredient and a dissolution regulating agent, wherein the said composition may be optionally covered with a readily soluble composition of
Tiaramide or its pharmaceutically acceptable salt, for efficient the reapy.
Namely, according to this invention, efficient therapy can be achieved by the less dosage and less administration times of Tiaramide or its pharmaceutically acceptable salt, since the serum concentration of Tiaramide or its pharmaceutically acceptable salt can be maintained for a long time by administration of the composition of this invention to human beings.
Suitable pharmaceutically acceptable salt of Tiaramideto be used in this invention may include hydrochloride and any other pharmaceutically acceptable acid addition salt.
Suitable "dissolution regulating agent" may include a mixture of a water-slightly soluble substance (e.g. (C1 to C6) alkyl cellulose such as ethyl cellulose, cellulose acetate, paraffin, etc.) and a water-soluble substance (e.g. polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxy (C1 to C6) alkyl cellulose compound such as hydroxypropyl methylcellulose or hydroxypropyl cellulose, etc.), and the like.
Suitable "readily soluble composition of
Tiaramide or its pharmaceutically acceptable salt", which is an optional portion of this invention, may be a conventional one used for usual oral administration such as powder, granules, tablets or the like.
And in case that this composition is used in tablets, the formulation of said composition may be the same as that of the marketted Tiaramide hydrochloride tablet.
According to this invention, in case that a long acting pharmaceutical composition comprises
Tiaramide or its pharmaceutically acceptable salt as an active ingredient and a dissolution regulating agent, the said composition can be used in a conventional pharmaceutical form, preferably in tablet.
In case that a long acting pharmaceutical composition of this invention comprises the composition comprising Tiaramide or its pharmaceutically acceptable salt as an active ingredient and a dissolution regulating agent and the readily soluble composition of Tiaramide or its pharmaceutically acceptable salt, the said composition can be also used in a conventional pharmaceutical form, preferably in dry coated tablets, wherein the outside of the composition comprising Tiaramide or its pharmaceutically acceptable salt and the dissolution regulating agent is covered with the readily soluble composition of Tiaramide or its pharmaceutically acceptable salt.
Amount of the "dissolution regulating agent" can be suitably selected according to a kind of the dissolution regulating agent. For example, in case that the dissolution regulating agent is a mixture of ethyl cellulose and polyethylene glycol, preferable amount of "ethyl cellulose" to "whole amount of the composition comprising Tiaramide or its pharamaceutically acceptable salt and the dissolution regulating agent" is 1 to 40 weight percent (more preferably 2 to 30 weight percent and most preferably 5 to 20 weight percent), and preferable amount of "polyethylene glycol" to "whole amount ofthe composition comprising Tiaramide or its pharmaceutically acceptable salt and the dissolution regulating agent" is 1 to 30 weight percent (more preferably 2 to 25 weight percent).
Amount of Tiaramide or its pharmaceutically acceptable salt to be contained in the composition of this invention can be suitably selected. For example, in case that Tiaramide hydrochloride is used as an active ingredient in this invention, preferable amount of "Tiaramide hydrochloride" to "whole amount of the composition comprising Tiaramide hydrochloride and the dissolution regulating agent" is 40 to 70 weight percent (more preferably 50 to 60 weight percent), and preferable amount of "Tiaramide hydrochloride" to "whole amount of the readily soluble composition of Tiaramide hydrochloride" is 10 to 30 weight percent (more preferably 10 to 20 weight percent).
In case that the long acting pharmaceutical composition of this invention comprises the composition comprising Tiaramide hydrochloride and the dissolution regulating agent and the readily soluble composition ofTiaramide hydrochloride, preferable ratio of "Tiaramide hydrochloride contained in the composition comprising Tiaramide hydrochloride and the dissolution regulating agent" to "Tiaramide hydrochloride contained in the readily soluble composition ofTiaramide hydrochloride" is 1:2 to 2:1.
The long acting pharmaceutical composition of this invention can be prepared in a conventional manner. The pharmaceutical composition ofthis invention may contain various organic or inorganic additives, which are conventionally used for the purpose of pharmaceutical preparation, such as excipient (e.g. lactose, starch, sucrose, etc.), binding agent (e.g. starch, hydroxypropyl cellulose, polyvinylpyrrolidone, gelatin, etc.), disintegrator (e.g. microcrystalline cellulose, starch, carboxymethyl cellulose, etc.), lubricant (e.g. talc, mag
Table 1 nesium stearate, etc.), or the like.
The following comparative test data are given to illustrate superiority of the pharmaceutical composition of this invention in comparison with the marketting Tiaramide hydrochloride tablet.
Experiment (1) Dissolution test
The each dissolution rate of the tablets obtained in
Examples of this invention and the marketting tablet (110 mgofTiaramide hydrochloride iscontained) was determined according to the rotating basket method tU.S.P. XIX Method I) under 100 r.p.m. with (a) simulated gastric juice (J.P. IX Disintegration Test
Solution Na. 1) (hereinafter referred to "Method A" or (b) simulated gastric juice (J.P. IX Disintegration
Test Solution No. 2) (hereinafter referred to "Method"
B") or (c) firstly with "Method A" for 1 hour and the "Method B" continuously (hereinafter referred to "Method C".
The results are shown in the following Table 1.
Dissolution rate (%) Tablet Method Time (hour) 113 0.5 1 2 3 4 5 6 7 8 Markettingtablet A 92 100 - Example A A - 25 40 48 55 63 68 73 79 Example 2 (A) B - - 28 46 60 73 81 88 93 99 Example 2 (B) B - - 27 42 53 63 73 78 88 93 Example 2 (C) B - - 23 33 42 51 56 63 67 72 Example 3 (90% C2HsOH B - - 29 46 59 69 74 79 83 85 Example3(85%C2H5OH) B - - 29 52 66 70 77 81 83 86 lExample3(80%C2H5OH) B - - 41 64 78 87 94 97 98 Example4 C - 13 27 51 65 75 83 89 Example 5 (300 mg) A - - 35 49 59 66 73 77 Example 5 (400 mg) A - - 33 45 54 62 67 72 Example A A - 35 47 57 63 69 73 77 Example C - 36 39 56 68- 76 82 86 90 93 (2) Bioavailabllity' test in dogs
The one tablet weighing 300 mg (165 mg of
Tiaramide hydrochloride is contained) obtained in
Example 5 of this invention and the two marketting tablets (total amount of Tiaramide hydrochlorid'e is
Table 2 165 mg) were orally dosed to 6 beagle dogs, respectively, and then the serum concentration of
Tiaramide was determined by gas-liquid chromatography.
The results were shown in the following Table 2.
Mean serum concentration (,zg/ml) ofTiaramide Tablet rime (hour) 0.5 1 2 4 6 8 10 12 24 Marketting tablet 0.6 3.2 4.1 1.3 0.7 0.6 0.6 - 0.2 Tablet (300 mg) of Example - 2.2 2.4 2.0 1.6 1.0 0.7 0.6 0.3 (3) Bioavailabilitytestin human beings
The one tablet (220 mg of Tiaramide hydrochloride is contained) obtained in Example 6 of this invention was orally dosed to 12 male volunteers and the two markettingtablets (one tablet contains 110 mg of
Tiaramide hydrochloride) were orally dosed twice to 12 male volunteers at the interval of 6 hours, respectively. After the first administration, the serum concentration of Tiaramide was determined by gasliquid chromatography, and the area under the serum concentration-time curve of Tiaramide was calculated.
The results were shown in the following Tables 3 and 4 and Figure 1.
Figure 1 shows the mean serum concentrations of
Tiaramide after single oral dosing with the tablet obtained in Example 6 of this invention and after twice oral dosing (Intervals: 6 hours) with the marketting tablet to twelve volunteers.
Table3 (Serum concentration of Tiaramide)
Mean serum concentration (,ag/ml) of Tiaramide Tablet Time (hour) 1 2 4 6 7 8 10 12 24 Marketting 0.46 0.33 0.09 0.03 0.37 0.35 0.12 0.03 0.01 tablet Tablet of 0.26 0.29 0.24 0.14 - 0.13 0.10 0.08 0.02 Example 6 Table 4 (Area underthe serum concentration-time
curve of Tiaramide)
Marketting tablet: 2.58,ag.ml ' .hour (mean)
Tablet of Example 6:: 2.59,ag.ml ' .hour (mean)
According to the above experimental results, it can be said that the long acting pharmaceutical composition of this invention is much superiortothe marketting tablet for efficient therapy of patients.
The following Examples are given to illustrate this invention, but this invention is not limited thereto.
Example 1
Each of Tiaramide hydrochloride (55 weight parts), ethyl cellulose (15 weight parts) and lactose (22 weight parts) is passed through a 16 mesh-sieve and these are blended for 10 minutes, and then kneaded with a solution of macrogol 6000 (polyethylene glycol) (7 weight parts) in 90 to 99% v/v aqueous solution of ethanol.
The resulting mixture was dried for 10 hours with chamber dryer at 40"C, granulated in 800 to 50ill size and then blended with magnesium stearate (1 weight part). The resulting mixture was granulated for tablets and then compressed into tablets weighing 200 mg. Thus obtained tablets, when desired, can be coated with sugar-coating or film-coating in a conventional manner.
Example 2
The following weight parts of ethyl cellulose and lactose were used instead of those in Example 1.
(A) (B) (C) ethyl cellulose 5 8 22
Lactose 32 29 15
Example 3
80% v/v or 85% v/v aqueous solution of ethanol was used instead of 90 to 99% v/v aqueous solution of ethanol in Example 1 or 2.
Example 4
The each tablet obtained in Example 1 was coated with coating liquid of hydroxypropyl methylcellulose phthalate (7.4 weight parts), triacetin (0.4 weight parts), isopropyl alcohol (46.1 weight parts and dichloromethane (46.1 weight parts) until the weight of the coating solid part of the tablet became 4.0 mg.
Example 5
Tablets weighing 400 mg or 300 mg were obtained by treating tiaramide hydrochloride (55 weight parts), ethyl cellulose (17.5 weight parts), lactose (20 weight parts), macrogol 6000 (polyethylene glycol) (6.5 weight parts) and magnesium stearate (1 weight part) in a similar manner to that in Example 1.
Example 6
The each tablet weighing 400 mg obtained in
Example 5 was coated with coating liquid of hydroxypropyl methylcellulose until the weight of the coating solid part of the tablet became 12 mg.
Example 7
(1) Tiaramide hydrochloride (14.3 weight parts), lactose (67 weight parts) and corn starch (17 weight parts) were blended and then kneaded with a sulution of metolose (1 weight part) in distilled water.
After the resulting mixture was dried and granulated to give a readily soluble composition of Tiaramide hydrochloride.
(2) The outside ofthe each tablet obtained in
Example 1 or 2 or 3 or 4 or 5 or 6 was covered with the readily soluble composition obtained in the above (1), and then compresses into dry coated tablet weighing 550 mg. The dry coated tablet was coated with coating liquid of polyvinylacetal diethylaminoacetate (7 weight parts) and ethanol (93 weight parts) until the weight of the coating solid part became 10 mg.
Claims (8)
1. A long acting pharmaceutical composition of
Tiaramide or its pharmaceutically acceptable salt which comprises Tiaramide or its pharmacuaticaily acceptable salt as an active ingredient and a dissolution regulating agent, wherein the said composition may be optionally covered with a readily soluble composition of Tiaramide or its pharmaceutically acceptable salt.
2. The pharmaceutical composition of claim 1, which comprises Tiaramide or its pharmaceutically acceptable salt and a dissolution regulating agent.
3. The pharmaceutical composition ofclaim 2, wherein the dissolution regulating agent is a mixture of a water-slightly soluble substance and a watersoluble substance.
4. The pharmaceutical composition of claim 3, wherein the dissolution regulating agent is a mixture of ethyl cellulose and polyethylene glycol.
5. The pharmaceutical composition of claim 4, which is tablet.
6. The pharmaceutical composition of claim 1, which comprises Tiaramide or its pharmaceutically acceptable salt as an active ingredient and a dissolution regulating agent and a readily solublecomposition of Tiaramide or its pharmaceutically acceptable salt.
7. The preparation of claim 6, wherein the outside of the composition comprising Tiaramide or its pharmaceutically acceptable salt and the dissolution regulating agent is covered with the readily soluble composition of Tiaramide or its pharmaceutically acceptable salt.
8. The preparation of claim 7, which is dry coated tablet.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13850679A JPS5661311A (en) | 1979-10-25 | 1979-10-25 | Thial amide or prolonged pharmaceutical preparation comprising its salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2061111A true GB2061111A (en) | 1981-05-13 |
Family
ID=15223717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8034222A Withdrawn GB2061111A (en) | 1979-10-25 | 1980-10-23 | Long acting pharmaceutical composition |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5661311A (en) |
| AU (1) | AU6325380A (en) |
| BE (1) | BE885806A (en) |
| DE (1) | DE3040042A1 (en) |
| FR (1) | FR2467596A1 (en) |
| GB (1) | GB2061111A (en) |
| IT (1) | IT1134039B (en) |
| NL (1) | NL8005873A (en) |
| NZ (1) | NZ195299A (en) |
| ZA (1) | ZA806383B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428951A (en) * | 1982-04-22 | 1984-01-31 | Fujisawa Pharmaceutical Co., Ltd. | Long acting pharmaceutical composition |
| NL8500724A (en) * | 1985-03-13 | 1986-10-01 | Univ Groningen | DEVICES FOR REGULAR RELEASE OF ACTIVE SUBSTANCES AND METHOD OF MANUFACTURE THEREOF |
| IT1200178B (en) * | 1986-07-23 | 1989-01-05 | Alfa Farmaceutici Spa | GALENIC FORMULATIONS WITH SCHEDULED SALE CONTAINING DRUGS WITH ANTI-FLOGISTIC ACTIVITY |
| IT1215726B (en) * | 1988-01-18 | 1990-02-22 | Alfa Wassermann Spa | GALENIC FORMULATIONS WITH SCHEDULED SALE. |
| US5840737A (en) | 1996-01-04 | 1998-11-24 | The Curators Of The University Of Missouri | Omeprazole solution and method for using same |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8906940B2 (en) | 2004-05-25 | 2014-12-09 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3388041A (en) * | 1964-01-27 | 1968-06-11 | Richardson Merrell Inc | High dosage sustained release tablet |
| JPS5495719A (en) * | 1978-01-09 | 1979-07-28 | Fujisawa Pharmaceut Co Ltd | Pharmaceutical composition containing tiaramide of its acid addition salt, and its preparation |
-
1979
- 1979-10-25 JP JP13850679A patent/JPS5661311A/en active Pending
-
1980
- 1980-10-14 AU AU63253/80A patent/AU6325380A/en not_active Abandoned
- 1980-10-16 ZA ZA00806383A patent/ZA806383B/en unknown
- 1980-10-20 NZ NZ195299A patent/NZ195299A/en unknown
- 1980-10-21 BE BE0/202538A patent/BE885806A/en not_active IP Right Cessation
- 1980-10-23 DE DE19803040042 patent/DE3040042A1/en not_active Withdrawn
- 1980-10-23 GB GB8034222A patent/GB2061111A/en not_active Withdrawn
- 1980-10-24 FR FR8022802A patent/FR2467596A1/en active Pending
- 1980-10-24 IT IT25577/80A patent/IT1134039B/en active
- 1980-10-24 NL NL8005873A patent/NL8005873A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ZA806383B (en) | 1981-10-28 |
| NL8005873A (en) | 1981-04-28 |
| BE885806A (en) | 1981-04-21 |
| NZ195299A (en) | 1983-06-14 |
| IT1134039B (en) | 1986-07-24 |
| FR2467596A1 (en) | 1981-04-30 |
| JPS5661311A (en) | 1981-05-26 |
| AU6325380A (en) | 1981-04-30 |
| IT8025577A0 (en) | 1980-10-24 |
| DE3040042A1 (en) | 1981-05-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |