IE53104B1 - Process for the control of the liberation of active materials from active material containing compositions - Google Patents
Process for the control of the liberation of active materials from active material containing compositionsInfo
- Publication number
- IE53104B1 IE53104B1 IE1201/82A IE120182A IE53104B1 IE 53104 B1 IE53104 B1 IE 53104B1 IE 1201/82 A IE1201/82 A IE 1201/82A IE 120182 A IE120182 A IE 120182A IE 53104 B1 IE53104 B1 IE 53104B1
- Authority
- IE
- Ireland
- Prior art keywords
- liberation
- active material
- viscosity
- active
- process according
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 15
- 239000011149 active material Substances 0.000 title claims description 30
- 239000000203 mixture Substances 0.000 title claims description 18
- 229920001477 hydrophilic polymer Polymers 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract 2
- 229940079593 drug Drugs 0.000 claims abstract 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 18
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 18
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 13
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 239000013543 active substance Substances 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract 2
- 238000013270 controlled release Methods 0.000 abstract 1
- 230000000630 rising effect Effects 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 230000000979 retarding effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229920006184 cellulose methylcellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229960005316 diltiazem hydrochloride Drugs 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000005624 silicic acid group Chemical class 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
- A01N25/10—Macromolecular compounds
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C05—FERTILISERS; MANUFACTURE THEREOF
- C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
- C05G3/00—Mixtures of one or more fertilisers with additives not having a specially fertilising activity
- C05G3/40—Mixtures of one or more fertilisers with additives not having a specially fertilising activity for affecting fertiliser dosage or release rate; for affecting solubility
- C05G3/44—Mixtures of one or more fertilisers with additives not having a specially fertilising activity for affecting fertiliser dosage or release rate; for affecting solubility for affecting solubility
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Chemical & Material Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Dentistry (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Materials For Medical Uses (AREA)
- Lock And Its Accessories (AREA)
- Slot Machines And Peripheral Devices (AREA)
- Valve-Gear Or Valve Arrangements (AREA)
Abstract
1. Process for the time controlled release of active substances from sustained-release active substance preparations, in particular drug preparations, by addition of hydrophilic polymers characterized in that the release rate which is rising as a result of increasing viscosity steps of the hydrophilic polymers added is empirically determined and the desired release characteristic is adjusted using the values determined.
Description
The present invention is concerned with a process for the timed control of the liberation of active materials from active material-containing compositions and especially from pharmaceutical compositions.
In pharmaceutical technology, it is known to incorporate active materials into pharmaceutical compositions in such a manner that the active . · materials are liberated from these compositions at a predetermined rate. In this way, it is possible, for example, to achieve a prolongation of the period· of action and thus to avoid too quick and/or too con-, centrated a release of the active material and too high peaks of the blood or tissue levels, which can lead to undesirable side effects.
If the good solubility or, in the case of peroral pharmaceutical products, also the good resorbability of the active material is the reason for too rapid a release, then the resorption of such an active material can be retarded by restricting the original solubility properties. In the simplest case, they can be achieved, for example, in the case of readily soluble substances by admixing poorly soluble adjuvant materials or by coating the substances with adjuvant materials which lower the solubility. Generally speaking, the rule applies that readily water-soluble substances must be worked up with poorly soluble adjuvant -3materials and poorly water-soluble substances with readily soluble or readily swellable adjuvant substances if a good retarding effect is to be achieved.
Such compositions are often additionally coated with diffusion coatings.
It is known that hydrophilic polymers can be used to produce the desired retarding effect.
From J. Pharm. Sci., 55, 974/1965, it is known, for example, that the desired retarding effect depends exclusively upon the formation of a viscous gel barrier which prevents the penetration of digestive juices into the interior of tablets.
Otherwise, hydrophilic polymers have hitherto only been used in pharmaceutical technology as binding agents in aqueous solution for achieving mechanically stable compressed bodies and those with a high swellability have been employed as so-called disintegrating agents for achieving a rapid breakdown of tablets in solid form.
For the expert, it was hitherto very difficult, when using swelling materials, for example guar gum, carob bean meal, semi-synthetic or synthetic polymers, such as silicic acids, cellulose acetate phthalate, hydroxypropylcellulose or carboxypolymethylene (Carbopol), to predict their influence on the liberation of an active substance from a pharmaceutical composition and -4hitherto extensive empirical experiments were first necessary in order to develop a retard form with a previously determined liberation characteristic of the active material.
It is an object of the present invention to adjust the liberation characteristic of retard form with the simplest of means in any desired manner, using a previously unknown principle, and thus to minimise the empirical experiments in the case of developments.
We have now, surprisingly, found that when using hydrophilic polymers, especially carboxymethyleellulose and methylcellulose, the differences of solubility or of swellability, due, perhaps, to the degree of substitution, have only a very small influence on the liberation of active materials from retard pharmaceutical compositions.
The expert would, on the basis of his knowledge of the prior art, actually have expected that in the case of the incorporation of, for example, carboxymethylcellulose into retard compositions, the degree of substitution would ba of considerable importance for the aberosion of compressed bodies and thus the liberation of active material involved therewith since the solubility or swellability of this adjuvant material depends directly upon the degree of substitution so that, -5upon contact with water of digestive juices, due to varyingly strong swelling and loosening up of the pharmaceutical compositions, a greatly differing rate of liberation ought to result. Completely unexpectedly, we have found that the liberation of the active material is essentially determined only by the degree of viscosity of the added hydrophilic polymers, the adjustment of a less retarded liberation of active material taking place, fully surprisingly, with highly viscous polymers, whereas with low viscous polymers the liberation of the active material is more strongly retarded.
Consequently, according to the present invention there is provided a process for the timed control of liberation of active material from a retarded active materialcontaining composition by the addition of a hydrophilic polymer, wherein the rate of liberation of active material which increases with increasing viscosity of the hydrophilic polymer added is empirically determined and the desired liberation characteristic is adjusted using the values so determined.
Especially preferred hydrophilic polymers include carboxymethylcelluloses (synonyms sodium carboxymethylcellulose, CMC, Na-celluloseglycolate) and methyl cellulose, which are widely available commercially.
They differ, on the one hand, by the degree of substitution and, on the other hand, within a certain range of S3 10 4 -6substitution, by the viscosity which, in. turn, is dependent upon the degree of polymerisation or upon the molecular weight. The viscosity of the conventional commercial products is determined in aqueous solution and is type-specified by the manufacturer.
The statements in the present description refer to the data supplied by the manufacturer and depend upon the viscosity determination, published in the Company's brochure of technical data for cellulose gum and its chemical and physical properties (cellulose gum No. 800-6A/G, Hercules, Wilmington, Del., U.S.A.).
Not only by the use of hydrophilic polymers of quite definite viscosity but also by the use of mixtures of polymers with different degrees of viscosity, the rate of liberation of active materials from solid retard compositions can now be varied and fixed in a previously unknown manner. In the case of the use of a thorough'mixing of, for example, carboxymethylcelluloses of differing viscosity, retard pro20 ducts are obtained, the course of liberation of which lies between the courses of liberation which the individual components would have given.
Carboxymethylcelluloses are, therefore, especially preferred for the process according to the present invention because these are commercially available in a large number of degrees of viscosity of from about 0.02 Pa.s. to about 40 Pa.s. and do not give rise to -7any problems with regard to their stability and compatibility with active materials and other adjuvant materials.
The process according to the present invention is advantageous for the development of retard pharmaceutical compositions since the carrying out of a large number of experiments can be avoided. Hitherto, in large series of experiments, it was necessary to find compositions which gave the necessary liberation of the active materials. The formulations were thereby either randomly selected and varied within the series of experiments or, according to a factor search plan, I certain influential factors were sought, each of which had to be varied at different levels. The planned experiments must thereby be carried out, the products obtained investigated and, on the basis of the results, the selection made for the next series of experiments.
When using the process according to the present invention, this work is, as a rule, either not necessary or is substantially reduced in extent; thus, after one preliminary experiment, the probably suitable viscosity stage of, for example, carboxymethylcellulose, can be sought. If the desired degree of active material liberation is thereby not obtained, then, by the use of mixtures of carboxymethylcelluloses with different degrees of viscosity, an appropriate degree of liberation can be adjusted. 310^ -8If this adjustment has taken place, then products are obtained, each of which are the same in their qualitative and quantitative composition and which only differ by the degree of viscosity of the carboxy5 methylcelluloses employed.
Since the products are of uniform composition, the working up properties are also the same. Thus, there is no danger that, in the case of variation of the degree of liberation, as previously, the physical properties, for example, the tabletability, would also change. The active material stability of such products is also the same for all degrees of viscosity and, consequently, no longer has to be separately determined for each variation in prolonged stability tests.
The amount of polymer to be added is, as a mile, from 0.1 to 10% by weight of the total mass of the composition. When using carboxymethylcelluloses, amounts in the range of from 0.5 to 3% by weight are preferred.
' The process according to the present invention can, in principle, also be applied to other active material-containing compositions, for example, animal bait, fertilisers and herbicides.
The following Examples are given for the purpose of illustrating the present invention:Exanrole 1. Ί00 g. of hydrogenated castor oil, 150 g. of -·9stearic acid and 750 g. lactose were homogeneously mixed with 10 g. amounts of carboxymethylcellulose of various stages of viscosity and then melt granulated in known manner. The following viscosity stages were thereby employed: a) 0.05 Pa.s. b) 0.3 Pa.s. c) 0.6 Pa.s. d) 3 Pa.s. e) 6 Pa.s. f) 20 Pa.s. g) 40 Pa.s.
All batches were then pressed with a medium, uniform pressure to give domed tablet's of 11 mm. diameter and 490 mg. weight. The breakdown of the tablets was investigated by the procedure described in the National Formulary XIV, p.935, in simulated gastric and duodenal juice, based upon their loss of weight, the residues of the tablets being determined at time intervale indicated on the abscissa of Figure 1 of the accompanying drawings, dried at 45°C. for 10 hours and weighed.
It can be seen from Figure 1 that the weight loss of the tablets is directly dependent upon the viscosity of the carboxymethylcellulose used.
Example ?.
This Example demonstrates the adjustment of a -10particular active material liberation on the basis of a predetermined specification.
In the manner described in Example 1, tablets were produced with a total weight of 300 mg. and with an active material content of SO mg. (diltiazem hydrochloride). The determination of the active material was made from the liquid medium at the time intervals indicated on the abscissa of Fig.2a of the accompanying drawings. Initially, use was made of a carboxymethylcellulose with a viscosity of 0.3 Pa.s., the results obtained being given in Fig.2a. The desired limits of liberation are shown in Fig.2b.
On the basis of the course of the curve in Fig.1, tablets were then investigated which had been prepared with the use of carboxymethylcellulose with a viscosity of 3 Pa.s. The results of the liberation testing are given in Fig.2c which show that the liberation takes place too quickly. The use of a carboxymethylcellulose with a viscosity of 0.6 Pa.s. gave a liberation characteristic lying exactly within the desired limits (Fig.2d). The same result was obtained when using a mixture of a carboxymethylcellulose with a viscosity of 0.3 Pa.s. with a carboxymethylcellulose with a viscosity of 3.0 Pa.s (see Fig.2e).
Claims (6)
1. A process for the timed control of the liberation of active material from a retarded active materialcontaining composition by the addition of a hydrophilic 5 polymer, wherein the rate of liberation of active material which increases with increasing viscosity of the hydrophilic polymer added is empirically determined and the desired liberation characteristic is adjusted using the values so determined. 10
2. A process according to Claim 1, wherein the active material is a drug.
3. A process according to Claim 1 or 2, wherein the hydrophilic polymer is methyl cellulose and/or carboxymethylcellulose. 15
4. A process according to any one of Claims 1 to 3, wherein the hydrophilic polymer used has a viscosity of from 0.02 to 40 Pa.s.
5. A process according to any of the preceding claims, wherein the viscosity is adjusted by mixing hydrophilic polymers with 20 different degrees of viscosity to a value lying between these degrees of viscosity. -12
6. A process according to Claim 1 for the timed control of the liberation of active material from a retarded active material-containing composition, substantially as hereinbefore described and exemplified.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813125178 DE3125178A1 (en) | 1981-06-26 | 1981-06-26 | METHOD FOR THE TIMED CONTROL OF THE RELEASE OF ACTIVE SUBSTANCES FROM ACTIVE SUBSTANCE PREPARATIONS, IN PARTICULAR DRUG PREPARATIONS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE821201L IE821201L (en) | 1982-12-26 |
| IE53104B1 true IE53104B1 (en) | 1988-06-22 |
Family
ID=6135462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1201/82A IE53104B1 (en) | 1981-06-26 | 1982-05-19 | Process for the control of the liberation of active materials from active material containing compositions |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0068446B2 (en) |
| JP (1) | JPS5843927A (en) |
| AT (1) | ATE16979T1 (en) |
| AU (1) | AU548792B2 (en) |
| CA (1) | CA1208556A (en) |
| DE (2) | DE3125178A1 (en) |
| DK (1) | DK173480B1 (en) |
| ES (1) | ES8308699A1 (en) |
| FI (1) | FI78391C (en) |
| HU (1) | HU189148B (en) |
| IE (1) | IE53104B1 (en) |
| SU (1) | SU1375114A3 (en) |
| ZA (1) | ZA824496B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8403361D0 (en) * | 1984-02-08 | 1984-03-14 | Erba Farmitalia | Pharmaceutical composition |
| GB8403360D0 (en) * | 1984-02-08 | 1984-03-14 | Erba Farmitalia | Pharmaceutical compositions |
| US4608248A (en) * | 1985-11-08 | 1986-08-26 | Warner-Lambert Company | Process for time-controlled release of active ingredients |
| DE3737741A1 (en) * | 1987-11-06 | 1989-05-18 | Goedecke Ag | ORAL MEDICAL FORM FOR THE ONLY DAILY TREATMENT OF HYPERTENSION WITH DILTIAZEMHYDROCHLORIDE |
| FR2630913A1 (en) * | 1988-05-09 | 1989-11-10 | Delalande Sa | DILTIAZEM WATER SOLUBLE SALT (S) COMPRESSES WITH PROGRAMMED RELEASE AND METHOD OF MANUFACTURING THE SAME |
| ES2036123B1 (en) * | 1990-12-03 | 1994-01-16 | Neila Nieto Jorge Juan | MANUFACTURING PROCESS OF SOLID INORGANIC FERTILIZERS CONDITIONED WITH WATER RETAINING POLYMERS. |
| ES2042418B1 (en) * | 1992-05-18 | 1994-07-01 | Tecno Holding S A | METHOD FOR THE EXTERNAL TREATMENT OF VEGETABLE CROPS. |
| US6440457B1 (en) | 1993-05-27 | 2002-08-27 | Alza Corporation | Method of administering antidepressant dosage form |
| GB2370775A (en) * | 2001-01-04 | 2002-07-10 | Nimrod Israely | Insecticidal composition based on attractant, insecticide and stabilizer, the outer surface of which expands & loses viscosity on contact with humidity |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1492019A1 (en) * | 1963-06-20 | 1969-02-20 | Ministerul Ind Petrolului Si C | Surcharge for medicinal tablets and methods of obtaining them |
| NL159577B (en) * | 1968-02-15 | 1979-03-15 | Organon Nv | PROCESS FOR PREPARING FAST DISINTEGRATING SOLID PARTS. |
| GB2042888B (en) * | 1979-03-05 | 1983-09-28 | Teijin Ltd | Preparation for administration to the mucosa of the oral or nasal cavity |
| US4226849A (en) * | 1979-06-14 | 1980-10-07 | Forest Laboratories Inc. | Sustained release therapeutic compositions |
| US4259314A (en) * | 1979-12-10 | 1981-03-31 | Hans Lowey | Method and composition for the preparation of controlled long-acting pharmaceuticals |
-
1981
- 1981-06-26 DE DE19813125178 patent/DE3125178A1/en not_active Ceased
-
1982
- 1982-05-19 IE IE1201/82A patent/IE53104B1/en not_active IP Right Cessation
- 1982-06-21 SU SU823452763A patent/SU1375114A3/en active
- 1982-06-24 DE DE8282105557T patent/DE3268012D1/en not_active Expired
- 1982-06-24 EP EP82105557A patent/EP0068446B2/en not_active Expired
- 1982-06-24 AT AT82105557T patent/ATE16979T1/en active
- 1982-06-24 ZA ZA824496A patent/ZA824496B/en unknown
- 1982-06-24 FI FI822276A patent/FI78391C/en not_active IP Right Cessation
- 1982-06-25 AU AU85361/82A patent/AU548792B2/en not_active Expired
- 1982-06-25 HU HU822074A patent/HU189148B/en unknown
- 1982-06-25 DK DK198202879A patent/DK173480B1/en active
- 1982-06-25 JP JP57108599A patent/JPS5843927A/en active Granted
- 1982-06-25 ES ES513422A patent/ES8308699A1/en not_active Expired
- 1982-06-25 CA CA000406024A patent/CA1208556A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FI822276L (en) | 1982-12-27 |
| HU189148B (en) | 1986-06-30 |
| AU548792B2 (en) | 1986-01-02 |
| JPH0569806B2 (en) | 1993-10-01 |
| DK173480B1 (en) | 2000-12-18 |
| DK287982A (en) | 1982-12-27 |
| EP0068446A3 (en) | 1983-07-20 |
| FI822276A0 (en) | 1982-06-24 |
| CA1208556A (en) | 1986-07-29 |
| ZA824496B (en) | 1983-04-27 |
| ES513422A0 (en) | 1983-10-01 |
| SU1375114A3 (en) | 1988-02-15 |
| EP0068446B2 (en) | 1988-12-07 |
| DE3125178A1 (en) | 1983-01-13 |
| ES8308699A1 (en) | 1983-10-01 |
| FI78391B (en) | 1989-04-28 |
| EP0068446A2 (en) | 1983-01-05 |
| ATE16979T1 (en) | 1986-01-15 |
| EP0068446B1 (en) | 1985-12-18 |
| JPS5843927A (en) | 1983-03-14 |
| IE821201L (en) | 1982-12-26 |
| AU8536182A (en) | 1983-01-06 |
| DE3268012D1 (en) | 1986-01-30 |
| FI78391C (en) | 1989-08-10 |
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