GB2098867A - Sustained release pharmaceutical composition - Google Patents
Sustained release pharmaceutical composition Download PDFInfo
- Publication number
- GB2098867A GB2098867A GB8214461A GB8214461A GB2098867A GB 2098867 A GB2098867 A GB 2098867A GB 8214461 A GB8214461 A GB 8214461A GB 8214461 A GB8214461 A GB 8214461A GB 2098867 A GB2098867 A GB 2098867A
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- GB
- United Kingdom
- Prior art keywords
- composition
- mixture
- indoramin
- sustained release
- pharmaceutically acceptable
- 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.)
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Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
Abstract
The invention provides a sustained release pharmaceutical composition comprising a mixture of micronised indoramin or a pharmaceutically acceptable salt thereof, a water-channelling agent and a wetting agent, the mixture being in the form of a non-compressed pellet and having an enteric coat or a sustained release coat permeable to gastrointestinal juices. Sustained release capsules are also provided comprising a plurality of the aforementioned pellets.
Description
SPECIFICATION
Sustained release pharmaceutical composition
This invention relates to sustained release pharmaceutical compositions containing indoramin or a pharmaceutically acceptable salt thereof.
In UK Patent Specification No. 1218570 there are described and claimed a class of indole derivatives which have various pharmacological activities, especially action on the cardiovascular system. One of these compounds, indoramin, (3-[2-(4-benzamido- 1 -piperidyl)ethyl]-indole), has demonstrated valuable antihypertensive properties in human beings. This compound is generally used in the form of its hydrochloride salt.
In the treatment of hypertensive patients where therapy continues for a considerable length of time it is desirable to employ sustained release compositions of an antihypertensive agent. This is because administration of the drug need not be as frequent as with ordinary release forms and can be reduced, for example, to once a day. As a result patient compliance with long term therapy is generally improved. Desirably sustained release forms achieve or approach steady state plasma therapeutic levels of the drug. With this aim in mind sustained release compositions are tailored to slowly, but completely release the drug in sufficient concentration into the gastrointestinal tract at a rate dependent on the dose frequency and gastrointestinal transit time (on average about 24 hours in the human).It is both desirable and a requirement for use in humans that a sustained release composition should be able to release at least about 80% of the drug present during transit. Formulations with less efficiency than this could have safety problems if unexpected complete release were to occur resulting in drug overdose from the 'excess' of drug present in the composition.
In attempts to prepare satisfactory sustained release formulations in pellet form containing indoramin using sustained release coatings and carriers, we have now found that dissolution of indoramin was occurring at excessively slow rates which were totally unsuitable for practical purposes.
This invention relates to pharmaceutical compositions of indoramin or a pharmaceutically acceptable salt thereof which can be used for sustained release over the gastrointestinal transit time and can provide high levels of drug release. Because the average gastric emptying time is known to be about 1 hour slow release during intestinal transit time (on average ca. 23 hours) may also be utilized in a therapeutically effective sustained release formulation. Therefore this invention also relates to a pharmaceutical composition having sustained release properties over the intestinal transit time.
Accordingly this invention provides a sustained release pharmaceutical composition comprising a mixture of micronised indoramin or a pharmaceutically acceptable salt thereof, a waterchannelling agent and a wetting agent, the mixture being in the form of a non-compressed pellet and having an enteric coat or a sustained release coat permeable to gastrointestinal juices.
By 'micronized indoramin' is meant indoramin in which the particle size has been reduced by comminution techniques employing for example fluid energy mills or roller mills, the former being preferred. It is preferred that the indoramin is micronized to a particle size in which 90% of particles are less than or equal to 1 5it most preferably less than or equal to 1 OIL, e.g. 5y or less.
By the term 'water-channelling agent' is meant an agent which facilitates the movement of water into the matrix of a dose form. We have found hydrophilic long chain polymers such as microcrystalline cellulose are particularly useful as exemplified by those sold under the
Registered Trade Mark AVICEL.
Examples of the wetting agents useful in the composition of this invention include anionic surfactants such as sodium alkyl sulphates, sodium laurate, dioctyl sodium sulphosuccinate, sodium stearate, potassium stearate and sodium oleate; non ionic surfactants such as polyethylene glycol and polyoxyethylene esters such as those sold under the Registered Trade Mark
TWEEN and cationic surfactants such as benzalkonium chloride and bis-2-hydroxyethyl oleylamine.
In a preferred dosage form, the composition of the invention is prepared by applying the ingredients, with adhesive, to an inert core which acts as a physical support, e.g. non-pareil seeds; and then providing a sustained release or enteric coating, preferably in the form of a film applied to the pellet.
In the compositions of the invention the degree of micronisation and the ratios of micronised indoramin or pharmaceutically acceptable salt thereof, water-channelling agent and wetting agent are adjustable so that at least about 80% dissolution of drug occurs in gastrointestinal media, within about 24 hours.
The ratio of micronized indoramin or pharmaceutically acceptable salt thereof to waterchannelling agent may be from about 30:1 to about 2:1, preferably about 10:1 to about 3:1.
The ratio of micronized indoramin or pharmaceutically acceptable salt thereof to wetting agent may be from about 300:1 to about 6:1, preferably about 150:1 to 30:1. Ratios used herein are on a w/w basis.
The amount of indoramin or pharmaceutically acceptable salt thereof present in the mixture (i.e. excluding the sustained release coat adhesive and any inert support) may comprise about 50 to 95% by weight, preferably 75 to 90% by weight. The water channelling agent may comprise up to about 25% by weight, preferably about 4 to 20% w/w of the composition and the wetting agent up to about 10% by weight, preferably about 0.5 to 3% by weight.
Examples of sustained release coats permeable to gastro-intestinal juices are known coats- such as natural waxes or mixtures of polymers especially mixtures of ethyl cellulose and a polymer selected from polyethylene glycol, hydroxypropyl cellulose, methyl cellulose, hydroxypropylmethyl cellulose and polyvinylpyrrolidone; or polyacrylate resins such as EUDRAGIT RL and RS.
The coat is preferably applied as a film by depositing a solution or suspension of the coating agent on the pellet followed by evaporation solvent carrier. However, other coat barriers are possible, e.g. enteric or sustained release coated carrier containing the pellet mixture.
Preferably the coating is a mixture of ethylcellulose (e.g. 6-50 cps) and polyethylene glycol (PEG) for example in the ratio ranging from about 9:1 to about 6:4 respectively. Preferably the molecular weight of the PEG ranges from 400 to 20,000 e.g. 2000 to 10,000. The coating may have, for example, up to about 50p thickness depending on the release profile desired and comprise up to 15% by weight of the total composition. Examples of enteric coats are any suitable coats known in the art such as film forming substances for example hydroxypropylmethyl cellulose phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate and acrylic resins. Plasticizers and lubricants may also be present. The coating may be sprayed onto the composition using a suitable solvent carrier.Typically the enteric coating comprises about 3 to about 20% w/w.
Advantageously the compositions also comprise a disintegrant, for exam'ple, modified starch such as that sold under the Trade Mark EXPLOTAB or a cross-linked polyvinyl pyrrolidone such as sold under the Trade Mark KOLLIDON CL. Preferred range for the disintegrant is up to 5% of the composition (excluding sustained release coating and any inert core).
In a particularly preferred aspect this invention provides a capsule or similar unit dosage form for slow release of indoramin or a salt thereof comprising a plurality of sustained release pellets according to the aforementioned composition of this invention, if desired the pellets having varying sustained release coat thicknesses and quantities of indoramin, water channelling agent and/or wetting agent, and further desired the capsule comprising a ready release quantity of indoramin or pharmaceutically acceptable salt thereof. Where an enteric coating is applied to the pellets it will obviously be desirable to incorporate the ready release quantity of indoramin in the capsule to provide a rapid therapeutical effect to the user.
This invention also provides a process for preparing a sustained release pharmaceutical composition which comprises intimately mixing micronised indoramin or a pharmaceutically acceptable salt thereof, a water channelling agent and a wetting agent; forming the mixture without compression into a pellet and providing an enteric or sustained release coat permeable to gastrointestinal juices. If desired pharmaceutical disintegrants, excipients, e.g. lactose may also be present in the mixture.
This invention further provides a process for preparing a sustained release capsule comprising encapsulating a plurality of pellets according to the aforementioned composition of this invention.
The following Examples describe the preparation and comparative testing of pellets according to this invention and illustrate the high levels of drug release found from our dissolution studies using an updated standard procedure designed to simulate the human gastrointestinal tract.
EXAMPLE 1
Preparation of Indoramin Hydrochloride Sustained Release Pellets
A. Indoramin Un coa ted Pellets
Place suitable size non pareil seeds (e.g. 840-500y,) in the appropriate size of coating pan.
Wet the seeds evenly by spraying on a ca. 5% adhesive solution of PVP in IPA. Apply some indoramin HCI coating powder blend to the seeds, mixing well while the pellets are rolling. Dry the pellets between coats with warm air for a few minutes. The quantities of adhesive solution and coating powder applications can proportionally be increased as the batch size increases.
Continue alternate applications of adhesive solution and powder until all the coating powder blend is applied. Allow the pellets to dry. Sieve the pellets through a 1 200 micron screen and over a 600 micron screen.
B. Cellulosic Coating Application
Transfer into a suitable fluidized bed stainless steel column. Spray with ethyl cellulose-PEG 4000 solution into the fluidized pellets at 40or. Spray continuously at the appropriate speed from a suitable pump and a suitable size spray nozzle. Turn on the extraction at intermittent intervals to remove vapours. Apply sufficient coating solution to increase the weight of coated pellets by the desired amount, e.g. 2-20%.
C. Using the above mentioned general procedure, pellets incorporating the composition of this invention were made by using the following ingredients:
Coating Powder Blend % w/w
Indoramin HCI micronized (90%S51l) 84
AVICEL pH 101 10
EXPLOTAB 5
Sodium Lauryl Sulphate 1 and applying to non-pareil seeds using ca. 5% PVP in isopropyl alcohol adhesive. A 4% w/w coating of ethyl-cellulose+10 cps)-PEG 4000 (8:2 w/w) sustained release coat was applied.
Final composition had 420 mg g-' indoramin HCI.
D. A comparative formulation not containing micronised indoramin, wetting agent or waterchannelling-agent was made up similarly using the following ingredients:
Coating Powder Blend % by weight
Indoramin HCI 85%
EXPLOTAB 5%
Talc BP 5%
Kaolin Light BP 5% and applied to non-pareil seeds using same adhesive as in 1C and coated to 4% w/w with same sustained release coating as 1 C.
Final composition had 450 mg g-' indoramin HCI.
EXAMPLE 2
Dissolution testing of compositions from EXAMPLES 1 C and 1D
The test method used was designed to model the human gastrointestinal tract. Pellets were added to dissolution medium (2 litres) which was preheated to 37 + 0.5 and stirred at 50 revs/min with a 7 cm Teflon paddle situated 2.5 cm above the bottom of a 3 litre round bottomed flask.
The medium used to determine the dissolution rate was an aqueous solution of chloride ions (120 mmoles 1 -'), the surface tension of which had been adjusted to 4X 10-2 Nm-' with
Tween 80 (100 mgl-1). The medium was initially made pH 1.5 by the presence of hydrochloric acid (0.06M) but after 1 hour the medium was changed to pH 7 by the replacement of 500 ml of the initial medium with a 500 ml solution of sodium hydroxide (0.24 M) and buffering salts of phosphate (ca. 0.20 M) (K2HPO4 and KH2PO4). 20 ml samples of the medium were taken at selected time intervals after the introduction of the pellets and replaced by fresh medium to maintain constant volume.
Each sample was filtered through a pre-washed 1 .2it millipore filter in Swinnex holder immediately prior to assay. Samples were by uv absorbance measurement at 280nm in 1 cm quartz cells. Comparison with standard solutions (5-3Ogml-1) allowed the mg indoramin released from each sampling time to be calculated by reference to the standard graph (concentration plotted against absorbance).
The results of the variable pH dissolution test are shown in the Table below:
TABLE 1
Percent by weight released after hours
Formulation pH 71 1 13 2 3 4 6 20-24 hrs
EXAMPLE 1C 1.5 12 21 (4% w/w coat) 7 33 38 49 57 * 96
EXAMPLE 1D 1.5 24 41 (4% w/w coat) 7 56 64 66 66 64 70 *= not measured.
The results show that the 4% w/w coated composition of Example 1 D had a relatively rapid release profile up to 2 hours followed by a virtual halt in release of indoramin for the remainder of the 24 hour time period. The similarly coated composition of Example 1C on the other hand had a more steady release profile. Additionally the composition of Example 1 C produced almost complete dissolution of the indoramin in the 24 hour time period whereas that of Example 1 D reached only 70% release in the same period.
EXAMPLE 3
Coated pellets on non-pareil seed cores (840-500IL) were prepared by the procedure described in Example 1 to the following formulations:
% Amount by weight (excluding weight
of core and adhesive)
Formulation: 3A 3B 3C 3D 3E 3F 3G
INGREDIENT:
Indoramin HCI
micronised 84 93.3 93.3 84.9 - 84 84
Non micronised
indoramin HCI - - - - 84 -
Avicel PH 101 10 - - 10.1 10 10 10
Explotab 5 5.6 5.6 5 5 - 5
Kollidon CL - - - - - 5
Sodium lauryl
sulphate 1 1.1 1.1 - 1 1 1 Potency of pellets as mg/g indoramin HCI 410 527 547 547 487 448 425
Seed size W 840- 595- 840- 700- 595- 595- 840
700 500 700 595 500 500 700 * Degree of micronisation 90% of particles 5lj Pellets 3A, 3B, 3C, 3D and 3E were given a sustained release coat, the coating solution containing 8% w/v ethyl cellulose and 2% w/v polyethylene glycol 4000. Pellets 3F and 3G were given an enteric coat, the coating solution containing 8% w/v hydroxypropylmethyl cellulose phthalate and 5% w/v glycerol triacetate.The pellets had the following coating weights:
Pellet: 3A 3B 3C 3D 3E 3F 3G
Coating weight: 4 3.2 3.3 3.6 4 10.3 10 (% w/w relative to uncoated pellet)
EXAMPLE 4
Dissolution studies were carried out on the pellets 3A-3G above according to the procedure described in Example 2, but modified slightly in the following manner:
(i) Surface tension was controlled using Tween 20 (100 mgl-1).
(ii) The change in pH was modified so that the final pH was 6.8 + 0.05 (not 7.0). This was achieved by the replacement of 1 litre of initial medium after 1 hour with 1 litre of a solution, at 37"C, of sodium hydroxide (0.12 M) and buffering salts of phosphate (ca. 0.1 M) (K2HPO4 and KH2PO4) (iii) A further 1 litre of medium was replaced at 6 hours with 1 litre of solution, at 37"C, of buffering salts of phosphate (0.05M) (K2HPO4 and KH2PO4) having a pH of 6.8.
The results of the variable pH dissolution test are tabulated below (TABLE 2) and some are also illustrated in the accompanying Figure 1.
TABLE 2
% (w/w) released after hours:
Formulation pH 3 1 13 2 3 4 6 7 8 10 24 3A 1.5 13 26
6.8 40 46 * 62 70 * * * 94 3B 1.5 7 14
6.8 30 35 44 48 53 * 53 * 3C 1.5 8 15
6.8 30 39 45 48 52 * 52 3D 1.5 21 32
6.8 43 46 50 52 55 * 56 * * 3E 1.5 4 9
6.8 24 33 40 44 49 * 51 * 3F 1.5 2 3
6.8 13 15 19 21 27 31 * 42 91 3G 1.5 < 1 2
6.8 21 33 44 52 62 75 * * 87 * = not measured.
Formulations 3A, 3F and 3G are all composition of the present invention and the dissolution results show that 3A, 3F and 3G achieve almost complete release of indoramin hydrochloride in the 24 hour time period.
Formulations 3B, 3C, 3D and 3E on the other hand virtually halted release of indoramin HCI after 3 hours. The difference in behaviour is more readily apparent from the accompanying Fig.
1 where the dissolution rates of formulations 3B, 3C, 3D and 3E are compared graphically with formulation 3A. Formulation 3A can be seen to be markedly superior from its ability to reach almost total release of indoramin HCI at the 24 hour time point.
By studying Table 2 and the formulations given in Example 3 it can be seen that the micronised indoramin, water channelling agent and wetting agent are essential ingredients if the desired, almost complete, dissolution is to occur over the 24 hour time period. Compare for example: 3A and 3B which show water channelling agent is essential; 3A and 3E which show micronisation is essential; and 3A and 3D which show wetting agent is essential.
Furthermore 3A and 3G show that either sustained release or enteric coats may be employed.
EXAMPLE 5
Pellets according to the invention, on non-pareil seed cores, are prepared by the procedure described in Example 1 and have the following formulations prior to coating with ethyl cellulose/PEG 4000 slow release coat:
% amount by weight*
Ingredient H I J K L M
Indoramin HCI 84 80 85 94 85 80 (micronised, 90%5IL) Avicel pH 101 10 15 13 5 13 15
Explotab 5 4
Sodium lauryl sulphate 1 2 1 5
Dioctyl sodium sulphosuccinate 1 2 * Excluding weight of core and adhesive.
Claims (29)
1. A sustained release pharmaceutical composition comprising a mixture of micronised indoramin or a pharmaceutically acceptable salt thereof, a water-channelling agent and a wetting agent, the mixture being in the form of a non-compressed pellet and having an enteric coat or a sustained release coat permeable to gastrointestinal juices.
2. A composition as claimed in Claim 1 in which the ratio of micronised indoramin or pharmaceutically acceptable salt thereof to water-channelling agent is from about 30:1 to about 2:1.
3. A composition as claimed in Claim 2 in which the ratio is from about 10:1 to about 3:1.
4. A composition as claimed in any one of Claims 1 to 3 in which the ratio of micronised indoramin or pharmaceutically acceptable salt thereof to wetting agent is from about 300:1 to about 6:1.
5. A composition as claimed in any one of Claims 1 to 4 in which the ratio of micronised indoramin or pharmaceutically acceptable salt thereof to wetting agent is from about 1 50:1 to 30:1.
6. A composition as claimed in any one of Claims 1 to 5 in which the micronised indoramin or pharmaceutically acceptable salt thereof has a particle size where 90% of the particles are less than or equal to 1 5it
7. A composition as claimed in Claim 6 wherein 90% of the particles are 5y or less.
8. A composition as claimed in any one of Claims 1 to 7 in which the indoramin or pharmaceutically acceptable salt thereof comprises about 50 to about 95% by weight of the mixture.
9. A composition as claimed in Claim 8 in which the indoramin or pharmaceutically acceptable salt thereof comprises about 75 to about 90% by weight of the mixture.
1 0. A composition as claimed in any one of Claims 1 to 9 in which the water-channelling agent is a hydrophilic long chain polymer.
11. A composition as claimed in any one of Claim 1 to 10 in which the water-channelling agent is micro-crystalline cellulose.
1 2. A composition as claimed in any one of Claims 1 to 11 in which the water-channelling agent comprises from about 4 to about 20% by weight of the mixture.
1 3. A composition as claimed in any one of Claims 1 to 1 2 in which the wetting agent comprises up to about 10% by weight of the mixture.
1 4. A composition as claimed in Claim 1 3 in which the wetting agent comprises from about 0.5 to 3% by weight of the mixture.
1 5. A composition as claimed in any one of Claims 1 to 14 in which the wetting agent is a sodium alkyl sulphate, sodium laurate, dioctyl sodium sulphosuccinate, sodium stearate, potassium stearate, sodium oleate, polyethylene glycol, a polyoxyethylene ester, benzalkonium chloride or bis-2-hydroxyethyl oleylamine.
1 6. A composition as claimed in any one of Claims 1 to 1 5 in which the pellet is prepared by applying the mixture in layers, bound by adhesive, to an inert core.
1 7. A composition as claimed in Claim 1 6 in which the inert core is a non-pareil seed of from about 500 to 840it diameter.
1 8. A sustained release pharmaceutical composition comprising a pellet formed by applying an intimate mixture comprising micronised indoramin hydrochloride in which 90% of the particles have a particle size 5y, a microcrystalline cellulose and a wetting agent, in layers bound by adhesive to an inert core; said pellet having a sustained release or enteric coat applied as a film, the ratios of indoramin hydrochloride to microcrystalline cellulose and wetting agent being in the range from 10:1 to 3:1 and 150:1 to 30:1 respectively.
1 9. A composition as claimed in Claim 1 7 or Claim 1 8 in which the coated pellets are from about 1200it to 600it in diameter.
20. A composition as claimed in any one of Claims 1 to 1 9 in which the sustained release coat comprises a natural wax, a polyacrylate resin or a mixture of ethyl cellulose and a polymer selected from polyethylene glycol, hydroxypropyl cellulose, methyl cellulose, hydroxypropylmethyl cellulose and polyvinylpyrrolidine.
21. A composition as claimed in any one of Claims 1 to 19 in which the enteric coat comprises hydroxypropylmethyl cellulose phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate or an acrylic resin.
22. A composition as claimed in Claim 20 or Claim 21 in which the coat comprises up to 20% by weight of the pellet.
23. A composition as claimed in any one of Claims 1 to 22 in which the mixture also comprises a disintegrant.
24. A composition as claimed in Claim 1 substantially as hereinbefore described in any one of formulations 1C, 3F, 3G, H, I, J, K, Land M.
25. A process for preparing a sustained release pharmaceutical composition which comprises intimately mixing micronised indoramin or a pharmaceutically acceptable salt thereof, a water channelling agent and a wetting agent forming the mixture without compression into a pellet and providing the pellet with an enteric coat or a sustained release coat permeable to gastrointestinal juices.
26. A process as claimed in Claim 25 in which the mixture is formed into a pellet by applying it to an inert core in layers bound by adhesive.
27. A process as claimed in Claim 26 substantially as hereinbefore described with reference to Example 1C.
28. A composition whenever prepared by a process as claimed in any one of Claims 1 5 to 27.
29. A sustained release pharmaceutical capsule comprising a plurality of pellets as claimed in any one of Claims 1 to 24 and 28, and optionally, a ready release quantity of indoramin or a pharmaceutically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8214461A GB2098867B (en) | 1981-05-21 | 1982-05-18 | Sustained release pharmaceutical composition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8115678 | 1981-05-21 | ||
| GB8214461A GB2098867B (en) | 1981-05-21 | 1982-05-18 | Sustained release pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2098867A true GB2098867A (en) | 1982-12-01 |
| GB2098867B GB2098867B (en) | 1984-10-24 |
Family
ID=26279556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8214461A Expired GB2098867B (en) | 1981-05-21 | 1982-05-18 | Sustained release pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2098867B (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4540566A (en) * | 1984-04-02 | 1985-09-10 | Forest Laboratories, Inc. | Prolonged release drug dosage forms based on modified low viscosity grade hydroxypropylmethylcellulose |
| GB2176999A (en) * | 1985-06-22 | 1987-01-14 | Stanley Stewart Davis | Multiparticulate sustained release medicament |
| DE3830749A1 (en) * | 1987-09-11 | 1989-03-30 | Squibb & Sons Inc | MEDICAMENT IN THE FORM OF HIGH MEDICAL CONCENTRATED CONCENTRATES AND METHOD FOR THE PRODUCTION THEREOF |
| US4927640A (en) * | 1985-10-11 | 1990-05-22 | Aktiebolaget Hassle | Controlled release beads having glass or silicon dioxide core |
| US4938968A (en) * | 1988-07-26 | 1990-07-03 | Norjec Development Associates, Inc. | Controlled release indomethacin |
| US4942040A (en) * | 1987-10-08 | 1990-07-17 | Aktiebolaget Hassle | Pharmaceutical preparation and a process for its preparation |
| US4957745A (en) * | 1985-10-11 | 1990-09-18 | Aktiebolaget Hassle | Pharmaceutical preparation |
| US4971805A (en) * | 1987-12-23 | 1990-11-20 | Teysan Pharmaceuticals Co., Ltd. | Slow-releasing granules and long acting mixed granules comprising the same |
| US5049394A (en) * | 1987-09-11 | 1991-09-17 | E. R. Squibb & Sons, Inc. | Pharmaceutical composition containing high drug load and method for preparing same |
| US5122384A (en) * | 1989-05-05 | 1992-06-16 | Kv Pharmaceutical Company | Oral once-per-day organic nitrate formulation which does not induce tolerance |
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US9974752B2 (en) | 2014-10-31 | 2018-05-22 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
| US10722473B2 (en) | 2018-11-19 | 2020-07-28 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
-
1982
- 1982-05-18 GB GB8214461A patent/GB2098867B/en not_active Expired
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4540566A (en) * | 1984-04-02 | 1985-09-10 | Forest Laboratories, Inc. | Prolonged release drug dosage forms based on modified low viscosity grade hydroxypropylmethylcellulose |
| GB2176999A (en) * | 1985-06-22 | 1987-01-14 | Stanley Stewart Davis | Multiparticulate sustained release medicament |
| GB2176999B (en) * | 1985-06-22 | 1989-07-12 | Stanley Stewart Davis | Sustained release medicament |
| US4927640A (en) * | 1985-10-11 | 1990-05-22 | Aktiebolaget Hassle | Controlled release beads having glass or silicon dioxide core |
| US4957745A (en) * | 1985-10-11 | 1990-09-18 | Aktiebolaget Hassle | Pharmaceutical preparation |
| DE3830749A1 (en) * | 1987-09-11 | 1989-03-30 | Squibb & Sons Inc | MEDICAMENT IN THE FORM OF HIGH MEDICAL CONCENTRATED CONCENTRATES AND METHOD FOR THE PRODUCTION THEREOF |
| GB2209669A (en) * | 1987-09-11 | 1989-05-24 | Squibb & Sons Inc | Pharmaceutical composition containing high drug load |
| US5049394A (en) * | 1987-09-11 | 1991-09-17 | E. R. Squibb & Sons, Inc. | Pharmaceutical composition containing high drug load and method for preparing same |
| GB2209669B (en) * | 1987-09-11 | 1992-02-12 | Squibb & Sons Inc | Pharmaceutical composition containing high drug load and method for preparing same |
| US4942040A (en) * | 1987-10-08 | 1990-07-17 | Aktiebolaget Hassle | Pharmaceutical preparation and a process for its preparation |
| US4971805A (en) * | 1987-12-23 | 1990-11-20 | Teysan Pharmaceuticals Co., Ltd. | Slow-releasing granules and long acting mixed granules comprising the same |
| US4938968A (en) * | 1988-07-26 | 1990-07-03 | Norjec Development Associates, Inc. | Controlled release indomethacin |
| US5296232A (en) * | 1989-05-05 | 1994-03-22 | Kv Pharmaceutical Company | Pharmaceutical formulation which does not induce tolerance |
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5122384A (en) * | 1989-05-05 | 1992-06-16 | Kv Pharmaceutical Company | Oral once-per-day organic nitrate formulation which does not induce tolerance |
| US5445829A (en) * | 1989-05-05 | 1995-08-29 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US10500162B2 (en) | 2014-10-31 | 2019-12-10 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10111839B2 (en) | 2014-10-31 | 2018-10-30 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
| US10292938B2 (en) | 2014-10-31 | 2019-05-21 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10292939B2 (en) | 2014-10-31 | 2019-05-21 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10449159B2 (en) | 2014-10-31 | 2019-10-22 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US9974752B2 (en) | 2014-10-31 | 2018-05-22 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
| US10507186B2 (en) | 2014-10-31 | 2019-12-17 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10512613B2 (en) | 2014-10-31 | 2019-12-24 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10512612B2 (en) | 2014-10-31 | 2019-12-24 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10568841B2 (en) | 2014-10-31 | 2020-02-25 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10688060B2 (en) | 2014-10-31 | 2020-06-23 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US11896722B2 (en) | 2014-10-31 | 2024-02-13 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| US10722473B2 (en) | 2018-11-19 | 2020-07-28 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2098867B (en) | 1984-10-24 |
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| Date | Code | Title | Description |
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| PE20 | Patent expired after termination of 20 years |
Effective date: 20020517 |