US3922338A - Tablets containing in their mass controlled-release micro-capsules and process for manufacture of said tablets - Google Patents

Tablets containing in their mass controlled-release micro-capsules and process for manufacture of said tablets Download PDF

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US3922338A
US3922338A US487042A US48704274A US3922338A US 3922338 A US3922338 A US 3922338A US 487042 A US487042 A US 487042A US 48704274 A US48704274 A US 48704274A US 3922338 A US3922338 A US 3922338A
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tablets
microcapsules
layers
layer
medial layer
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Yvette Fr M J Estevenel
Maurice H Thely
Wladimir A Coulon
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Choay SA
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Choay SA
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    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50

Definitions

  • the present invention relates to new tablets for administration of medicaments, which tablets contain in their mass, controlled-release microcapsules, that is to say elemental particles coated with a protective covering which contains an encapsulated product which is gradually released in a controlled, regular and timedependent way.
  • the present invention relates to new tablets containing in their mass, controlled-release microcapsules and to the method of manufacture of such tablets.
  • the pharmaceutical industy has, for a long time, attempted to solve the problem of prolonging the period of effective action of medicaments. This problem is particularly important in the case where the period of effective action is short and also if there is a problem of conditioning two substances, or mixtures of substances, which are incompatible with one another in the same tablet especially when it would be advantageous to administer these substances in association with one another.
  • the multi'layer tablets which have been produced with the object of constituting controlled-release types of medicament comprise a plurality of superposed layers, the most common number of layers being three. Each of these layers has such a composition that the medicaments are liberated at intervals of time which are spaced apart.
  • three layers are again usually provided, which comprise a thin central layer of an inert substance which separates two layers of much greater thickness, which contain the incompatible medicaments.
  • the multi-layer tablets already known which are of the controlled-release type that is to say, tablets which release the active ingredients in a controlled manner over a period of time, suffer from the disadvantage that it cannot be ensured that the active constituent is liberated in a programmed manner at sufficiently regular intervals.
  • microcapsules comprise elemental particles of small dimensions, that is to say, having dimensions from a few microns to several millimeters. These microcapsules may be in a solid or liquid state and may be coated with a protective covering to form a micropackage. This micro-package is capable of being destroyed by mechanical or any bio-chemical action, at the time when it is desired to use the micro-packaged substance. Alternatively, the structure thereof may be such that it constitutes a coating through which the active constituent is progressively liberated.
  • the protective coating covering the elemental particles is obtained either by chemical or mechanical methods of encapsulation.
  • the coatings of microcapsules which are intended to act in a controlled-release manner over a period of time, are prepared by methods known per se. In particular, it is possible to regulate the rate of external diffusion of the encapsulated product by different methods. It is particularly possible to vary the thickness, to a greater or lesser extent, of the coating and, above all, by providing the coating with a predetermined micro-porosity.
  • microcapsules are relatively fragile structures.
  • a tablet is, of course, a very convenient form of administration since it reduces the volume to be swallowed by a patient.
  • an abrasive effect is noticed. This affects the external layer of the microcapsules and leads to at least a partial destruction of the microcapsule. This, accordingly, affects the quality of the controlled-release effect desired.
  • the direct pressing of the microcapsule irrespective of whether or not the microcapsule is of the double core coating type, has the effect of destroying its external and internal structure and the tablet obtained loses all its effectiveness.
  • the object of the present invention is to provide new tablets which contain controlled-release microcapsules in their mass, which respond better to the necessities of the art than controlled-release agents previously known.
  • new tablets containing, in their mass, controlledrelease microcapsules, characterised in that they are constituted by the association of a plurality of superposed layers, of which the medial layer is essentially constituted by microcapsules containing an active substance, whilst the exterior layers which may possibly also contain identical or different active substances and which have a composition usual for the making of tablets constitute means of protecting the microcapsules of the medial layer, particularly against the shock of compression.
  • the tablets in accordance with the invention have a hardness of the order of 10 to 20 kg on their surface and of theorder of 8 to 16 kg on their periphery.
  • the ratio between the sum of the thicknesses of the external layers and the thickness of the medial layer containing the microcapsules is advantageously between 0.8 and 4 and preferably between 1 and 2.4.
  • a method of making tablets containing, within their mass, controlled-release microcapsules character ised in that they are prepared in a tablet-making machine, a first external layer which essentially comprises excipients, and possibly therapeutically active substances which is subjected to a light compression, by simple levelling, for example, in that an internal layer superposed on the first external layer is prepared, the internal layer essentially comprising microcapsules containing an active substance, which internal layer is subjected to a light compression, by simple levelling, for example, in that a second external layer is prepared, of which the composition is identical to or different from, that of the first external layer, which is superposed on the internal layer of microcapsules, after which the superposed layers are subjected to compression in a machine for making tablets, which exerts a pressure force capable of giving rise to tablets of which the cohesion is sufficient to ensure the disintegration of the tablet in accordance with the conditions required by the French Pharmacopoeia.
  • the microcapsules containing an active substance are associated, in the medial layer, with an excipient which favors the disintegration of the microcapsules.
  • the thickness of each of the external layers must be between O.8 and 2 millimeters and preferably between 1 and 1.2 millimeters.
  • the tablets obtained in accordance with the present invention have associated therewith the advantage inherent in their presentation in the form of tablets, that is to say, the administration of active substances in a small volume together with the advantage of microcapsules, that is to say, a controlledrelease of one or more active substances in a programmed manner with respect to time.
  • composition adapted to form the external layers of the final tablet is prepared.
  • This composition essentially comprises excipients to which may possibly be added active substances; the excipients advantageously comprise an excipient of appropriate charge, for example, a microcrystalline a-cellulose such as that which is known under the trade name of AVICEL PH 102 (sold particularly by the firm *SEPlC), associated with a corn starch and with a lubricant such as for example, a mixture of monodiand tri-palmitostearic esters of glycerol such as those which are sold (by Etablmaschines GATTEFOSSE) under the trade name of 4 PRECIROL.
  • AVICEL PH 102 sold particularly by the firm *SEPlC
  • a lubricant such as for example, a mixture of monodiand tri-palmitostearic esters of glycerol such as those which are sold (by Etablmaschines GATTEFOSSE) under the trade name of 4 PRECIROL.
  • compositions into such a composition can be introduced active substances which are incompatible with those contained in the microcapsules, or active substances which are immediate-acting compared with the active substances contained in the microcapsules which act progressively over a period of time.
  • the composition may contain active substances which act at a level of gastro-intestinal transit different from that of the substance contained in the microcapsules.
  • This composition is put into the form of granules whichh have a grain size identical to that of the microcapsules, so that the free flow in the tablet machine can be identical in the two compositions.
  • a composition adapted to form the medial layer of the final tablet is then prepared by association of the microcapsules containing the active substance, with an excipient which improves the free flow and which facilitates the disintegration and, in so doing, the splitting of the tablets.
  • Half of the quantity of the external layer composition is introduced into the matrix of a tabletmaking machine, in which it is subjected to a light compression with a punch which is just sufficient to level this first external layer.
  • the medial layer composition prepared is superposed thereon. This is then subjected to a light compression with a punch, which is, again, just sufficient to level it.
  • a second external layer constituted by the other half of the external layer composition is then superposed on the medial layer containing the microcapsules.
  • the assembly of the three superposed layers is then subjected, in a tablet-making machine, to a com pressive force which is a function, in particular, of the nature of the products being made into tablets, and which produces tablets having a hardness, when measured on a Stokes apparatus, lying within the range of 10 to 20 kg on its surface and of 8 to 16 kg around its periphery.
  • a hardness value is sufficient, in the pharmaceutical condition art, to ensure the wholeness of the microcapsules is preserved.
  • the tablets thus obtained are advantageously flat and bevelled having a diameter of the order of ll mm, a final weight of between 0.360 and 0.660 grams, and a final total thickness of between 3.3 and 5.65 mm, the thickness of each of the external layers being between 0.8 and 2 mm if the thickness of the medial layer is of the order of 0.6 to 3 mm and preferably between 1 and 2 mm.
  • the invention also comprises other embodiments, which will be apparent from the following description.
  • EXAMPLE 1 A composition adapted to form the external layers of the final tablet is prepared by mixing the following constituents in the proportions stated:
  • microcrystalline a-cellulosc (known under the trade name ofA ⁇ /ICEL PH 102') Q.s.p. 0.260 g
  • This mixture is put into the form of granules of a grain size identical to that of the microcapsules, in such a manner that the dispersion in the tablet making machine of this composition is identical to that of the microcapsules.
  • the granules obtained have a grain size less than 1000 a.
  • composition adapted to form the medial layer of the final tablet is prepared, by mixing the following constituents in the proportions stated:
  • Active constituent Microcapsules enclosing papaverine chlorhydrate of the order of 0.097 g Filler excipient favoring free flow such as AVlCEL PH 102 for example Q.s.p. 0.140 g 3. a. 0.130 g of the composition described in (l) is placed into the matrix of a tablet machine, and is subjected to a pressing, by levelling for example, with the aid of the suitable means such as the punch of the machine, without, however, supplying a compressive force to this latter.
  • the composition described in (2) is superposed and this is also subjected to a pressing, by levelling for example, with the aid of suitable means such as the punch of the machine, in such a manner that the punch only exerts the compressive force exercised by its own weight.
  • the multi-layer composition thus obtained comprising a medial layer of microcapsules protected by two external layers, is submitted to a suitable compressive force in a tablet machine in such a manner as to obtain tablets having a hardness sufficient to be pharmaceutically satisfactory whilst nevertheless permitting a disintegration conforming to the standards laid down in the French Pharmacopoeia and preserving the programmed controlled-release of the active constituents.
  • the tablet obtained by using the method which has just been described is a flat tablet, chamfered, having a diameter of l 1 mm, a final thickness of 3.8 mm and a final weight of 0.400 g. This disinegrates in a period of 35 minutes.
  • the thickness of each of the external layers is 1.07 mm whilst the thickness of the microcapsule layer is 1.65 mm.
  • the hardness of this tablet measured on Strokes apparatus is kg on its surface and 5 kg on its periphery.
  • the tablets in accordance with the present invention which have just been described cause the immediate liberation of the therapeutic agents contained in their external layers and the controlled-release, over a prolonged period of time, up to 8 hours, of the papaverine contained in the microcapsules of the medial layer.
  • One practical application shows a particular interest in the case of medicaments of which the therapeutic action is transient, such as is the case with papaverine, be cause it allows a progressive controlled-release of the papaverine in the patient, and thus maintains a constant amount of medicament.
  • the application of the new pharmaceutical form in accordance with the present invention, to the administration of other medicaments of which the therapeutic action is fleeting, such as adrenaline, and trinitrine, is of major interest.
  • the present invention also shows a great interest in the case where it is desired to administer one substance which it is desired to maintain at a regular level in the patient for a long period of time, without having to greatly increase the number of doses or by giving extremely large doses; this being the case, for example, with hypnotic or tranquilizing substances.
  • the form of administration in accordance with the present invention is also particularly interesting in that it allows the association of microcapsules with other therapeutic substances, notably in that it allows association of two or more substances of which the actions are complementary or potentialise one another, such as is the case with the association of a delaying product and a non-delaying product, or with the association of a hypnotic agent having immediate action with a hypnotic agent having a delayed action.
  • EXAMPLE 2 Other excipients besides AVICEL PH 102 described in Example 1 have been tested in association with the microcapsules of the medial layer containing the active constituent, such as papaverine chlorhydrate as described in Example 1. The efficiency of those excipients has been studied. The efficiency criterion chosen in the tests which will be described hereinafter, is the time release in vitro of micro-encapsulated papaverine chlorhydrate. This is a function of the excipient associated with the microcapsules. This test has made it clear, in the first place of the role of the excipient, which plays a complementary role in the protection of the microcapsules, preventing these latter from sticking together and from being damaged during the preparation of the tablets, which have the result of affecting the controlled-release effect.
  • compositions of the gastric and intestinal medias are those described on pages 1026 and 1027 respectively of the American Pharmacopoeia.
  • the pH of the gastric medium is adjusted to 1.6 and the pH of the intestinal medium is adjusted to 5.0. However, this latter does not contain any pancreatin, which is inactive at this pH.
  • the sample is immersed for an hour in a bath containing only the gastric medium at 37C. Every hour thereafter, half the volume of the bath is removed and replaced by an-equal volume of intestinal medium.
  • Example 3 The compositions described in Example I are prepared, and by putting into operation the process de- Multilayered tablets in accordance with the invention Micro- Standard "AVICEL” Maize Alginate POEG '71 of capsules tablet starch Starch +AV
  • the accompanying drawing shows the curves obtained corresponding to Table I, to wit:
  • the curve S corresponds to standard type tablets, that is to say, to tablets comprising microcapsules containing papaverine chlorhydrate, made, as
  • Curves I to IV relate to multi-layer tablets in accordance with the invention, in which:
  • Curve I the active constituent of the medial layer is associated with AVICEL and corn starch;
  • Curve II the active constituent of the medial layer is associated with maize starch
  • Curve III the active constituent of the medial layer is associated with alginates
  • Curve IV the active constituent of the medial layer is associated with AVICEL PH 102 and polyoxyethyleneglycol.
  • Compressed layered tablets containing, in their mass, controlled-release microcapsules comprising the association of a plurality of superposed layers, of which the medial layer essentially comprises microcapsules containing an active substance, while the exterior layers, which have a microcrystalline cellulose, starch, alginate, or polyoxy ethylene glycol tablet excipient composition, constitute means of protecting the microcapsules of the medial layer, particularly against the shock of compression, said tablet excipient composition being in the form of granules having the same grain size as said microcapsules.
  • Tablets according to claim 1 wherein said tablets have a hardness of the order of 10 to 20 kg on their surface and of the order of 8 to 16 kg on their periphery.

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  • Pharmacology & Pharmacy (AREA)
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US487042A 1973-07-12 1974-07-10 Tablets containing in their mass controlled-release micro-capsules and process for manufacture of said tablets Expired - Lifetime US3922338A (en)

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FR7325531A FR2236483B1 (es) 1973-07-12 1973-07-12

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JP (1) JPS5736893B2 (es)
BE (1) BE817401A (es)
CA (1) CA1028622A (es)
DE (1) DE2433285C2 (es)
ES (1) ES428171A1 (es)
FR (1) FR2236483B1 (es)
GB (1) GB1469879A (es)
IT (1) IT1016413B (es)
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Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4139589A (en) * 1975-02-26 1979-02-13 Monique Beringer Process for the manufacture of a multi-zone tablet and tablet manufactured by this process
US4316884A (en) * 1979-01-25 1982-02-23 Adria Laboratories, Inc. Sustained release pharmaceutical formulation
US4415547A (en) * 1982-06-14 1983-11-15 Sterling Drug Inc. Sustained-release pharmaceutical tablet and process for preparation thereof
US4532123A (en) * 1982-03-04 1985-07-30 Battelle Development Corporation Dual Microcapsules and process for their preparation
US4637905A (en) * 1982-03-04 1987-01-20 Batelle Development Corporation Process of preparing microcapsules of lactides or lactide copolymers with glycolides and/or ε-caprolactones
US4710384A (en) * 1986-07-28 1987-12-01 Avner Rotman Sustained release tablets made from microcapsules
US4720387A (en) * 1983-06-22 1988-01-19 Shionogi & Co., Ltd. Sustained-release preparation of pinacidil
US4748023A (en) * 1983-01-26 1988-05-31 Egyt Gyogyszervegyeszeti Gyar Process for the preparation of sustained release pharmaceutical compositions having a high active ingredient content
DE3825693A1 (de) * 1987-07-28 1989-02-09 Squibb & Sons Inc Arzneimittel mit kontrollierter wirkstoffabgabe
US4863741A (en) * 1985-03-25 1989-09-05 Abbott Laboratories Tablet composition for drug combinations
US4874614A (en) * 1985-03-25 1989-10-17 Abbott Laboratories Pharmaceutical tableting method
US4940588A (en) * 1984-10-30 1990-07-10 Elan Corporation Controlled release powder and process for its preparation
US4961890A (en) * 1986-08-08 1990-10-09 Ethypharm Method of preparing comtrolled release fenofibrate
US5019302A (en) * 1986-03-12 1991-05-28 Washington University Technology Associates, Inc. Method for granulation
US5202159A (en) * 1990-12-27 1993-04-13 Standard Chemical & Pharmaceutical Corp., Ltd. Preparation method of microdispersed tablet formulation of spray-dried sodium diclofenac enteric-coated microcapsules
US5330767A (en) * 1985-02-07 1994-07-19 Takeda Chemical Industries, Ltd. Sustained release microcapsule
US5476663A (en) * 1983-11-04 1995-12-19 Takeda Chemical Industries, Ltd. Prolonged release microcapsule
US5593696A (en) * 1994-11-21 1997-01-14 Mcneil-Ppc, Inc. Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders
US5817340A (en) * 1992-12-01 1998-10-06 Mcneil-Ppc, Inc. Pharmaceutical compositions containing famotidine and aluminum hydroxide or magnesium hydroxide
US20020147150A1 (en) * 1992-12-07 2002-10-10 Takeda Chemical Industries, Ltd. Sustained-release preparation
US6663896B1 (en) 2001-08-01 2003-12-16 Alvin S. Blum Delayed release aspirin for vascular obstruction prophylaxis
DE10306468A1 (de) * 2003-02-14 2004-09-02 Henkel Kgaa Aus Pulver und Mikrokapseln gepreßter Formkörper
US20050019391A1 (en) * 2001-11-05 2005-01-27 Edouard Gendrot Orodispersible tablet having high homogeneity and the preparation method thereof
US20080286344A1 (en) * 2007-05-16 2008-11-20 Olivia Darmuzey Solid form

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DE3228533A1 (de) * 1982-07-30 1984-02-02 Council of Scientific and Industrial Research, 110001 New Delhi Verfahren zur herstellung von medizinischen pillen und so hergestellen pillen
JPS61501197A (ja) * 1984-03-29 1986-06-19 レツペル−プラステイク　ゲゼルシヤフト　ミツト　ベシユレンクテル　ハフツング 印刷物の積み降ろし装置
EP0418596A3 (en) * 1989-09-21 1991-10-23 American Cyanamid Company Controlled release pharmaceutical compositions from spherical granules in tabletted oral dosage unit form
JPH0539288U (ja) * 1991-10-31 1993-05-28 三栄源エフ・エフ・アイ株式会社 容器兼用食品
ATE401868T1 (de) * 2004-08-04 2008-08-15 Alza Corp ZUSAMMENSETZUNG MIT VERZÖGERTER ARZNEIMITTELFREISETZUNG MIT EINEM AUFSTEIGENDEN NULLORDNUNG-FREIGABE-MUSTER; VERFAHREN ZUR HERSTELLUNG EINER SOLCHEN ZUSAMMENSETZUNGß

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US462990A (en) * 1891-11-10 William oppenheimek
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US3096248A (en) * 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3341416A (en) * 1963-12-11 1967-09-12 Ncr Co Encapsulation of aspirin in ethylcellulose and its product
US3488418A (en) * 1965-11-18 1970-01-06 Sterling Drug Inc Sustained relief analgesic composition
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US462990A (en) * 1891-11-10 William oppenheimek
US3048526A (en) * 1958-08-04 1962-08-07 Wander Company Medicinal tablet
US3096248A (en) * 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3341416A (en) * 1963-12-11 1967-09-12 Ncr Co Encapsulation of aspirin in ethylcellulose and its product
US3488418A (en) * 1965-11-18 1970-01-06 Sterling Drug Inc Sustained relief analgesic composition
US3524910A (en) * 1965-11-18 1970-08-18 Sterling Drug Inc Sustained relief analgesic compositions

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4139589A (en) * 1975-02-26 1979-02-13 Monique Beringer Process for the manufacture of a multi-zone tablet and tablet manufactured by this process
US4316884A (en) * 1979-01-25 1982-02-23 Adria Laboratories, Inc. Sustained release pharmaceutical formulation
US4532123A (en) * 1982-03-04 1985-07-30 Battelle Development Corporation Dual Microcapsules and process for their preparation
US4637905A (en) * 1982-03-04 1987-01-20 Batelle Development Corporation Process of preparing microcapsules of lactides or lactide copolymers with glycolides and/or ε-caprolactones
US4415547A (en) * 1982-06-14 1983-11-15 Sterling Drug Inc. Sustained-release pharmaceutical tablet and process for preparation thereof
US4748023A (en) * 1983-01-26 1988-05-31 Egyt Gyogyszervegyeszeti Gyar Process for the preparation of sustained release pharmaceutical compositions having a high active ingredient content
US4720387A (en) * 1983-06-22 1988-01-19 Shionogi & Co., Ltd. Sustained-release preparation of pinacidil
US5631020A (en) * 1983-11-04 1997-05-20 Takeda Chemical Industries, Ltd. Method for producing microcapsule
US5476663A (en) * 1983-11-04 1995-12-19 Takeda Chemical Industries, Ltd. Prolonged release microcapsule
US5631021A (en) * 1983-11-04 1997-05-20 Takeda Chemical Industries, Ltd. Method for producing microcapsule
US4940588A (en) * 1984-10-30 1990-07-10 Elan Corporation Controlled release powder and process for its preparation
US4952402A (en) * 1984-10-30 1990-08-28 Elan Corporation, P.L.C. Controlled release powder and process for its preparation
US5330767A (en) * 1985-02-07 1994-07-19 Takeda Chemical Industries, Ltd. Sustained release microcapsule
US4863741A (en) * 1985-03-25 1989-09-05 Abbott Laboratories Tablet composition for drug combinations
US4874614A (en) * 1985-03-25 1989-10-17 Abbott Laboratories Pharmaceutical tableting method
US5019302A (en) * 1986-03-12 1991-05-28 Washington University Technology Associates, Inc. Method for granulation
US4710384A (en) * 1986-07-28 1987-12-01 Avner Rotman Sustained release tablets made from microcapsules
US4961890A (en) * 1986-08-08 1990-10-09 Ethypharm Method of preparing comtrolled release fenofibrate
DE3825693A1 (de) * 1987-07-28 1989-02-09 Squibb & Sons Inc Arzneimittel mit kontrollierter wirkstoffabgabe
US5202159A (en) * 1990-12-27 1993-04-13 Standard Chemical & Pharmaceutical Corp., Ltd. Preparation method of microdispersed tablet formulation of spray-dried sodium diclofenac enteric-coated microcapsules
US5817340A (en) * 1992-12-01 1998-10-06 Mcneil-Ppc, Inc. Pharmaceutical compositions containing famotidine and aluminum hydroxide or magnesium hydroxide
US20020147150A1 (en) * 1992-12-07 2002-10-10 Takeda Chemical Industries, Ltd. Sustained-release preparation
US20020173467A1 (en) * 1992-12-07 2002-11-21 Takeda Chemical Industries, Ltd. Sustained-release preparation
US6528093B1 (en) 1992-12-07 2003-03-04 Takeda Chemical Industries, Ltd. Sustained-release preparation
US7048947B2 (en) 1992-12-07 2006-05-23 Takeda Pharmaceutical Company Limited Sustained-release preparation
US5593696A (en) * 1994-11-21 1997-01-14 Mcneil-Ppc, Inc. Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders
US6663896B1 (en) 2001-08-01 2003-12-16 Alvin S. Blum Delayed release aspirin for vascular obstruction prophylaxis
US20050019391A1 (en) * 2001-11-05 2005-01-27 Edouard Gendrot Orodispersible tablet having high homogeneity and the preparation method thereof
DE10306468A1 (de) * 2003-02-14 2004-09-02 Henkel Kgaa Aus Pulver und Mikrokapseln gepreßter Formkörper
US20080286344A1 (en) * 2007-05-16 2008-11-20 Olivia Darmuzey Solid form

Also Published As

Publication number Publication date
IT1016413B (it) 1977-05-30
SE7409149L (sv) 1975-01-13
NL7409295A (nl) 1975-01-14
JPS5036619A (es) 1975-04-05
DE2433285A1 (de) 1975-01-30
GB1469879A (en) 1977-04-06
JPS5736893B2 (es) 1982-08-06
DE2433285C2 (de) 1985-02-07
CA1028622A (fr) 1978-03-28
SE419161B (sv) 1981-07-20
AU7117574A (en) 1976-01-15
ES428171A1 (es) 1976-07-16
FR2236483A1 (es) 1975-02-07
BE817401A (fr) 1975-01-09
FR2236483B1 (es) 1976-11-12

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