CA1208556A - Process for time controlled release of active ingredients from active material containing pharmaceutical preparations - Google Patents
Process for time controlled release of active ingredients from active material containing pharmaceutical preparationsInfo
- Publication number
- CA1208556A CA1208556A CA000406024A CA406024A CA1208556A CA 1208556 A CA1208556 A CA 1208556A CA 000406024 A CA000406024 A CA 000406024A CA 406024 A CA406024 A CA 406024A CA 1208556 A CA1208556 A CA 1208556A
- Authority
- CA
- Canada
- Prior art keywords
- liberation
- viscosity
- active material
- hydrophilic polymer
- material containing
- 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
Links
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)
- Chemical & Material Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Agronomy & Crop Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Lock And Its Accessories (AREA)
- Slot Machines And Peripheral Devices (AREA)
- Valve-Gear Or Valve Arrangements (AREA)
- Materials For Medical Uses (AREA)
Abstract
ABSTRACT
The present invention provides a process for the timed control of the liberation of active material from a retarded active material-containing composition by the addition of a hydrophilic polymer, wherein the rate of liberation is adjusted by means of the viscosity of the added hydrophilic polymer, the rate of liberation increasing with increasing viscosity.
The present invention provides a process for the timed control of the liberation of active material from a retarded active material-containing composition by the addition of a hydrophilic polymer, wherein the rate of liberation is adjusted by means of the viscosity of the added hydrophilic polymer, the rate of liberation increasing with increasing viscosity.
Description
12(~85W
The present invention is concerned with a process for the timed oontrol of the liberation of active materials from active material-containing com~ositions and especially from pharmaceutical compositions.
In pharmaceutical technology, it is known to incorporate active material~ 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 ~uick 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 e~fects.
If the good solubility or, in the case of peroral pharmaceutical products, al~o the good resorb~
ability of the active material is the reason for too rapid a release, then the resorption of such an active material can be retarded by re~tricting the original solubility properties. In the simplest ca~e, 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 ~2(~8556 materials and poorly water-solubie substances with readily soluble or readily swellable adjuvant sub-st~nces if a good retarding e~fect 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, 974/1966, it is known, for example, that the desired retarding effe~t 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 bindins agents in aqueous solution for achieving mechanically stable compres~ed bodies and those with a high swell-ability have been employed as so-called disintegrating agents for achieving a rapid breakdown of tablets in s~lid form.
For the expert, it was hitherto very difficult, when u~ing ~welling material~, for example guar gum, carob bean meal, semi-synthetic or synthetic polymers, such a~ silicic acids, cellulose acetate phthalate, A hydroxypropylcellulose or carboxypolymethylene (~ar~p31 ), to predict their influence on the liberation of an active substance from a pharmaceutical composition and 120855~
hitherto 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 minimie the empirical experiments in the case of developments.
We have now, surprisingly, found that when using hydrophilic polymers, ecpecially caxboxymethyl-cellulose and methylcellulose, the differences of solubility or of swellability, due, perhaps, to the degree of substitution, have only a very smail influence on the liberation of active materials from retard pharmaceu~ical 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, carboxy-methylcellulose into retard compositions, the degree of eubstitution would be of con~iderable importance for the aberosion of compressed bodies and thus the liberation of active material involved therewith since the solubility or swellability of thiq adjuvant material depends directly upon the degree of substitution so that, 12~)~
upon contact with water or digestive juices, due to va~yingly 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 acti~e material taking place, fully surprisingly, with highly viscou~ polymers, whereas with low vi~cous polymers the liberation of the active material is more ~trongly retarded.
Consequently, according to the present inver.tion, there is provided a process for the timed control of the liberation of active material from a retarded active material-containing composition and especially from a pharmaceutical composition by the addition of a hydrophilic polymer, wherein the rate of liberation is adjusted by means of the viscosity of the added hydrophilic polym~r, the rate of liberation increasing with increasing vi~cosity.
Especially preferred hydrophilic polymers include carboxymethylcelluloses (synonym: sodium carboxymethyl-cellulose, CMC, Na-celluloseglycolate) and methyl cellulose, which are widely available commercially.
They differ, on the one hand, by the degree of substit-ution and, on the other hand, within a certain range of ~208SS~
substitution, by the viscosity which, in turn, is dependent upon the degree of polvmerisation or upon t~e molecular weight. The viscosity cf the convent-ional commercial products is detPrmined 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.
~00-6A/G, Hercules, Wilmington, Del., U.S.A.).
Not only by the use of hydrophilic polymers of ~uite definite viscosity but al~o by the use of mixtures of polymers with different degrees of vi~cosity, the rate of liberation of active materials from solid retard compositions can now be varied and fixed in a previously unknown manner. In the ca~e of the use of a thorough mixing of, for example, carboxy-methylcelluloses of differing viscosity, retard pro-ducts are obtained, the cour~e of liberation of which lie~ between the courses of liberation which the individual components would have given, Carboxymethylcellulose~ are, therefore, ecpecially preferred for the procesC according to the present invention because these are commercially available in a large number of degrees of viscosity of from about 0.02 Pa. 5, to about 40 Pa.s. and do not give rise to - ~20~;6 any 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 o, retard pharma-ceutical compositions since the carrying out of a large number of experiments can be avoided. $itherto, in large series of experiments, it was necessary to find compositions which gave the necessary liberation of t~e active materials. The fonmulations were thereby either randomly selected and varied within the series of experiments or, according to a factor search plan, 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 i8, as a rule, either not necess-ary or is substantially reduced in extent, thus, after one preliminary experiment, the probably suitable viscosity stage of, ~or example, carboxymethylcellulo~e, can be sought. If the de~ired 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 liber-ation can be adjusted.
8 ~2~
If this adjustment has taken place, then products are obtained, each of which are the same in their qualltative and quantitative composition and which only differ by the degree of viscosity of the carboxymethylcelluloses 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 stabil-ity tests.
The amount of polymer to be added is, as a rule, 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-contain-ing compositions, for example, animal bait, fertilisers and herbicides.
The ollowing Examples are given for the purpose of illustrating the present invention.
Figure 1 graphically illustrates the results of Example 1.
Figures 2A to 2E graphically illustrate the results of Example 2.
Example 1.
_ 100 g. of hydrogenated caster oil, 150 g. of lcm/ ~
1208S~
g stearic acid and 750 g. lactose were homogeneously mix~d with 10 g. amounts of carboxymethylcellulose of various stages of viscosity and then melt granulated in known manner. The Lollowing viscosity stages were thereby employed:
a~ 0~05 Pa7s.
b) 0.3 Pa.s.
c) 0.6 Pa.s.
d) 3 ~a.s.
e) 6 Pa.s.
f) 20 Pa.s.
g) 40 Pa.s.
All batches were then pres~ed with a medium, uniform pressure to give domed tablets 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.985, in simulated gastric and duodenal juice, ba~ed upon their loss of weight, the residue~ of the tablets being determined at time intervals indicated on the absci~sa of Figure 1 of the accompanying dra~ings, dried at 45C.
~or 10 hours and weighed.
It can be seen ~rom Figure 1 that the weight 109s of the tablets is directly dependent upon the viscosity of the carboxymethylcellulose used.
Exam~le 2.
This Example demonstrates the adjustment of a `` ~2085S6 particular active material liberation on the basis of a predetermined specification.
In the manner described in Exampl~ 1, tablets were produced with a total weight of 300 mg. and with an active material content of 50 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 carboxymethylcellulo~e 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 ~ig.l, 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. 9. gave a liberation characteristic lying exactly within the desired limits ~Fig.2d). ~he ~ame result was obtained when using a mixture of a carbo~ymethylcellulose with a viscosity of 0.3 Pa.s. with a carboxymethylcellulose with a viscosity of 3.0 Pa.s ~see Fig.2e).
The present invention is concerned with a process for the timed oontrol of the liberation of active materials from active material-containing com~ositions and especially from pharmaceutical compositions.
In pharmaceutical technology, it is known to incorporate active material~ 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 ~uick 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 e~fects.
If the good solubility or, in the case of peroral pharmaceutical products, al~o the good resorb~
ability of the active material is the reason for too rapid a release, then the resorption of such an active material can be retarded by re~tricting the original solubility properties. In the simplest ca~e, 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 ~2(~8556 materials and poorly water-solubie substances with readily soluble or readily swellable adjuvant sub-st~nces if a good retarding e~fect 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, 974/1966, it is known, for example, that the desired retarding effe~t 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 bindins agents in aqueous solution for achieving mechanically stable compres~ed bodies and those with a high swell-ability have been employed as so-called disintegrating agents for achieving a rapid breakdown of tablets in s~lid form.
For the expert, it was hitherto very difficult, when u~ing ~welling material~, for example guar gum, carob bean meal, semi-synthetic or synthetic polymers, such a~ silicic acids, cellulose acetate phthalate, A hydroxypropylcellulose or carboxypolymethylene (~ar~p31 ), to predict their influence on the liberation of an active substance from a pharmaceutical composition and 120855~
hitherto 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 minimie the empirical experiments in the case of developments.
We have now, surprisingly, found that when using hydrophilic polymers, ecpecially caxboxymethyl-cellulose and methylcellulose, the differences of solubility or of swellability, due, perhaps, to the degree of substitution, have only a very smail influence on the liberation of active materials from retard pharmaceu~ical 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, carboxy-methylcellulose into retard compositions, the degree of eubstitution would be of con~iderable importance for the aberosion of compressed bodies and thus the liberation of active material involved therewith since the solubility or swellability of thiq adjuvant material depends directly upon the degree of substitution so that, 12~)~
upon contact with water or digestive juices, due to va~yingly 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 acti~e material taking place, fully surprisingly, with highly viscou~ polymers, whereas with low vi~cous polymers the liberation of the active material is more ~trongly retarded.
Consequently, according to the present inver.tion, there is provided a process for the timed control of the liberation of active material from a retarded active material-containing composition and especially from a pharmaceutical composition by the addition of a hydrophilic polymer, wherein the rate of liberation is adjusted by means of the viscosity of the added hydrophilic polym~r, the rate of liberation increasing with increasing vi~cosity.
Especially preferred hydrophilic polymers include carboxymethylcelluloses (synonym: sodium carboxymethyl-cellulose, CMC, Na-celluloseglycolate) and methyl cellulose, which are widely available commercially.
They differ, on the one hand, by the degree of substit-ution and, on the other hand, within a certain range of ~208SS~
substitution, by the viscosity which, in turn, is dependent upon the degree of polvmerisation or upon t~e molecular weight. The viscosity cf the convent-ional commercial products is detPrmined 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.
~00-6A/G, Hercules, Wilmington, Del., U.S.A.).
Not only by the use of hydrophilic polymers of ~uite definite viscosity but al~o by the use of mixtures of polymers with different degrees of vi~cosity, the rate of liberation of active materials from solid retard compositions can now be varied and fixed in a previously unknown manner. In the ca~e of the use of a thorough mixing of, for example, carboxy-methylcelluloses of differing viscosity, retard pro-ducts are obtained, the cour~e of liberation of which lie~ between the courses of liberation which the individual components would have given, Carboxymethylcellulose~ are, therefore, ecpecially preferred for the procesC according to the present invention because these are commercially available in a large number of degrees of viscosity of from about 0.02 Pa. 5, to about 40 Pa.s. and do not give rise to - ~20~;6 any 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 o, retard pharma-ceutical compositions since the carrying out of a large number of experiments can be avoided. $itherto, in large series of experiments, it was necessary to find compositions which gave the necessary liberation of t~e active materials. The fonmulations were thereby either randomly selected and varied within the series of experiments or, according to a factor search plan, 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 i8, as a rule, either not necess-ary or is substantially reduced in extent, thus, after one preliminary experiment, the probably suitable viscosity stage of, ~or example, carboxymethylcellulo~e, can be sought. If the de~ired 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 liber-ation can be adjusted.
8 ~2~
If this adjustment has taken place, then products are obtained, each of which are the same in their qualltative and quantitative composition and which only differ by the degree of viscosity of the carboxymethylcelluloses 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 stabil-ity tests.
The amount of polymer to be added is, as a rule, 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-contain-ing compositions, for example, animal bait, fertilisers and herbicides.
The ollowing Examples are given for the purpose of illustrating the present invention.
Figure 1 graphically illustrates the results of Example 1.
Figures 2A to 2E graphically illustrate the results of Example 2.
Example 1.
_ 100 g. of hydrogenated caster oil, 150 g. of lcm/ ~
1208S~
g stearic acid and 750 g. lactose were homogeneously mix~d with 10 g. amounts of carboxymethylcellulose of various stages of viscosity and then melt granulated in known manner. The Lollowing viscosity stages were thereby employed:
a~ 0~05 Pa7s.
b) 0.3 Pa.s.
c) 0.6 Pa.s.
d) 3 ~a.s.
e) 6 Pa.s.
f) 20 Pa.s.
g) 40 Pa.s.
All batches were then pres~ed with a medium, uniform pressure to give domed tablets 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.985, in simulated gastric and duodenal juice, ba~ed upon their loss of weight, the residue~ of the tablets being determined at time intervals indicated on the absci~sa of Figure 1 of the accompanying dra~ings, dried at 45C.
~or 10 hours and weighed.
It can be seen ~rom Figure 1 that the weight 109s of the tablets is directly dependent upon the viscosity of the carboxymethylcellulose used.
Exam~le 2.
This Example demonstrates the adjustment of a `` ~2085S6 particular active material liberation on the basis of a predetermined specification.
In the manner described in Exampl~ 1, tablets were produced with a total weight of 300 mg. and with an active material content of 50 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 carboxymethylcellulo~e 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 ~ig.l, 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. 9. gave a liberation characteristic lying exactly within the desired limits ~Fig.2d). ~he ~ame result was obtained when using a mixture of a carbo~ymethylcellulose with a viscosity of 0.3 Pa.s. with a carboxymethylcellulose with a viscosity of 3.0 Pa.s ~see Fig.2e).
Claims (4)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the time-controlled liberation of an active material from a retarded active material-containing composition by the addition of a hydrophilic polymer, wherein the rate of liberation is adjusted by means of the viscosity of the added hydrophilic polymer, the rate or liberation increasing with increasing viscosity.
2. The process according to claim 1, wherein the hydrophilic polymer is selected from the group consisting of methyl cellulose, carboxymethyl cellulose and mixtures thereof.
3. The process according to claim 1 or 2, wherein the hydrophilic polymer used has a viscosity of from 0.02 to 40 Pa.s.
4. The process according to claim 1 or 2, wherein the viscosity is adjusted by mixing hydrophilic polymers with different viscosities to obtain a viscosity value for the mixture between said viscosities.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3125178.1 | 1981-06-26 | ||
| 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 (1)
| Publication Number | Publication Date |
|---|---|
| CA1208556A true CA1208556A (en) | 1986-07-29 |
Family
ID=6135462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000406024A Expired CA1208556A (en) | 1981-06-26 | 1982-06-25 | Process for time controlled release of active ingredients from active material containing pharmaceutical preparations |
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 |
|---|---|---|---|---|
| GB8403360D0 (en) * | 1984-02-08 | 1984-03-14 | Erba Farmitalia | Pharmaceutical compositions |
| GB8403361D0 (en) * | 1984-02-08 | 1984-03-14 | Erba Farmitalia | Pharmaceutical composition |
| 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 ZA ZA824496A patent/ZA824496B/en unknown
- 1982-06-24 FI FI822276A patent/FI78391C/en not_active IP Right Cessation
- 1982-06-24 EP EP82105557A patent/EP0068446B2/en not_active Expired
- 1982-06-24 AT AT82105557T patent/ATE16979T1/en active
- 1982-06-24 DE DE8282105557T patent/DE3268012D1/en not_active Expired
- 1982-06-25 HU HU822074A patent/HU189148B/en unknown
- 1982-06-25 JP JP57108599A patent/JPS5843927A/en active Granted
- 1982-06-25 ES ES513422A patent/ES8308699A1/en not_active Expired
- 1982-06-25 DK DK198202879A patent/DK173480B1/en active
- 1982-06-25 AU AU85361/82A patent/AU548792B2/en not_active Expired
- 1982-06-25 CA CA000406024A patent/CA1208556A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AU8536182A (en) | 1983-01-06 |
| FI78391C (en) | 1989-08-10 |
| FI822276A0 (en) | 1982-06-24 |
| EP0068446A3 (en) | 1983-07-20 |
| ES513422A0 (en) | 1983-10-01 |
| EP0068446A2 (en) | 1983-01-05 |
| IE53104B1 (en) | 1988-06-22 |
| DE3125178A1 (en) | 1983-01-13 |
| IE821201L (en) | 1982-12-26 |
| FI78391B (en) | 1989-04-28 |
| SU1375114A3 (en) | 1988-02-15 |
| AU548792B2 (en) | 1986-01-02 |
| EP0068446B1 (en) | 1985-12-18 |
| ATE16979T1 (en) | 1986-01-15 |
| ES8308699A1 (en) | 1983-10-01 |
| DK173480B1 (en) | 2000-12-18 |
| DE3268012D1 (en) | 1986-01-30 |
| FI822276L (en) | 1982-12-27 |
| HU189148B (en) | 1986-06-30 |
| DK287982A (en) | 1982-12-27 |
| ZA824496B (en) | 1983-04-27 |
| JPH0569806B2 (en) | 1993-10-01 |
| EP0068446B2 (en) | 1988-12-07 |
| JPS5843927A (en) | 1983-03-14 |
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| Date | Code | Title | Description |
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| MKEX | Expiry |