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Publication numberUS2857313 A
Publication typeGrant
Publication dateOct 21, 1958
Filing dateMar 27, 1956
Priority dateMar 27, 1956
Publication numberUS 2857313 A, US 2857313A, US-A-2857313, US2857313 A, US2857313A
InventorsCooper Jack, Pasquale Daniel Mario, Windheuser John Joseph
Original AssigneeCiba Pharm Prod Inc
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Self-lubricating granulation
US 2857313 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

United States Patent 2,857,313 SELF-LUBRICATIN G GRANULATION Jack Cooper, Summit, Daniel Mario Pasquale, Livingston, and John Joseph Windheuser, Milton, N. J., assignors to Ciba Pharmaceutical Products, Inc., Summit, N. J., a corporation of New Jersey No Drawing. Application March 27, 1956 Serial No. 574,103

6 Claims. (Cl. 16782) This invention relates to a new and improved method for preparing tablet granulations.

In the manufacture of compressed tablets, two methods are generally used. The most common is the so-called wet granulation process. This is a long and tedious operation requiring many steps. It includes moistening a mixture consisting of the therapeutic component, excipients and binder with a suitable moistening agent, passing the wet mass through a screen to form granules, drying and rescreening the granules in order to reduce them to a size suitable for use in a tableting machine. At this point a lubricating agent is homogeneously admixed with the granulation in order to facilitate its passage through various orifices in the tableting machine.

Another method for the preparation of compressed tablets is one commonly referred to as slugging. This method includes mixing the active ingredients with suitable excipients, compressing the dry powdered mass into large tablets or slugs, reducing the slugs to granules by forcing them through a screen of appropriate mesh size and recompressing the granules on a tableting machine.

Thus, in the case of the wet granulation process, it has heretofore been thought necessary to include -in the wet mass only the drug, excipients and binder and to add the lubricant to the dried granulation in a separate step. If the slugging method is used, the lubricant can be added in the initial mixing step but it is necessary to recompress the slugs after they have been granulated. It is also customary to add an additional lubricant before recompression to the final tablet shape.

Contrary to the teachings of the art at the present time, we have found that the lubricant can be added to the initial powdered mixture and can be subjected to wet granulation. The incorporation of the lubricant in the initial mixture, as well as the wetting and drying of it, in no way detract from its lubricating properties. This is an unexpectedand surprising observation, inasmuch as it has been though that the dry free-flowing consistency of the lubricant can be retained only if its contact with .moistening agents is completely avoided. Our discovery that the lubricating properties of lubricants are not affected by moisture and drying, not only eliminates a step which heretofore has been considered essential in the preparation of tablet granulations, but affords a considerable saving in time in the overall tableting process.

An additional advantage in incorporating the lubricant in the initial pro-granulated mixture resides in the efficacy of the tableting operation. Where, as before, it was necessary to subject the granulation to an additional mixing step, thus reducing the control over the accuracy of dosage per unit and increasing the probability of error, contamination and loss, it is now possible to make tablets by a process which is more accurate, more efficient, and less time-consuming. Tablets prepared in accordance with our process do not vary in hardness, have optimal disintegration time, are smooth and readily extrudable by the machine. Pitting and jamming, because of lack of lubricant in the granulation, have not been observed.

2,857,313 Patented Oct. 21, 19 58 Lubricants considered to be suitable in the operation of our process are talc, stearic acid, salts of this acid, preferably magnesium stearate and mixtures thereof. The amount of lubricant in relation to the total weight of the tablet depends largely upon the nature of the lubricant employed, and for this reason may vary within certain prescribed limits. For example, if talcum is employed, it is preferable to use about 5% to 10% of the lubricant. If magnesium stearate is used, the limits are somewhat narrower in range, being from 0.5 to 2%. In the case of stearic acid one may use a quantity varying from about 2% to about 5%. If mixtures of these are used, the proportions will vary in accordance with the respective quantities employed.

The method we have described here may be advantageously applied to a wide variety of tableting formulae tions wherein the use of a lubricating agent is mandatory. Therapeutically active compounds which may be formulated in accordance with our improved method include tripelennamine, methyl-phenidylacetate, phenobarbital, aspirin, reserpine, glutethimide, hydrocortisone, cortisone and other substances usually administered in tablet form.

Excipients suitable for use in our process are milk sugar, corn starch or other therapeutically inert substances commonly employed for this purpose. As binders, to insure adequate cohesive properties, may be used sucrose, gelatin, acacia or tragacanth. If desired, a water-soluble polyethylene glycol such as Carbowax 6000 may be added to provide added binding properties. Water, a lower alkanol such as methyl, ethyl, propyl or isopropyl alcohol, acetone, or mixtures thereof may be advantageously used as moistening agents in our process.

The following examples are intended to illustrate this invention but are not intended to be limitative upon the scope thereof.

Example 1 100 grams of methyl phenidylacetate hydrochloride,

grams of confectioners sugar, 75 grams of talcum and 7.5 grams of magnesium stearate are mixed in a suitable container until homogeneous. 75 grams of polyethylene glycol 6000 are dissolved in 100 ml. water and the mixture is diluted with 100 ml. anhydrous 3A alcohol, heating, if necessary, to a temperature of about 45 C. to effect solution. The mixed powders are granulated with the polyethylene glycol solution, additional 50% 3A alcohol being added when necessary. The moist mass is pressed through a No. 10 sieve and is dried. The resultant granules are passed through a No. 16 mesh screen and compressed into tablets.

Example 2 884 grams of lactose, 20 grams of tragacanth, 20 grams of acacia and 25 grams of talcum are mixed in a suitable container to a homogeneous mixture. 50 grams of polyethylene glycol 6000 are dissolved in'a solution containing 60 cc. of distilled water and 20 cc. of anhydrous 3A alcohol. The mixture of powders is granulated with the polyethylene glycol solution, passed through a No. 10 mesh screen, air-dried, passed through a No. 20 mesh screen and compressed into tablets.

Example 3 the steps of adding alubricating. agent, in: an: effective:

amount up to and includingv about %,.by weight, of

the resulting granules to a dry, powdered mixture of. a. therapeutic compound and an-excipient, moistening said? mixture with a solvent containing a binding agent andv forming the resulting massinto granules.

2. In a method forv preparing granules of therapeutically active substances, the improvement which comprises the steps of adding a lubricating agent, in an efiective amount;

up to and including about 10%, by weight,.of. the. resulting granules to a dry, powderedimixture' of a therapeutic compound. and an excipient,. moistening said. mixture with a solvent containing a binding lubricating agent,

and forming theresulting mass into granules;

3. In a method for preparing granules ottlierapeutically active substances, the improvement which comprises the:

step of moistening a dry, powdered mixture'of. a'therapeutic compound and an excipient with a mixture'of. a

solvent containing a binding-lubricating agent,.said.agent having an effective amount of lubricant up to-and:includ-' ing about l0% by weight,,of the resulting,granu1es, and' forming the resulting mass into'granules;

4. In a method for preparing granules of therapeutically active substances, the improvement which comprises the:

steps of moistening a dry, powdered mixture of athera- A peutic compound, an excipient and a lubricating agent; in an. effective amount up to and including about 10%, by weight, of the resulting granules with a solvent containing a binding agent, and forming the resulting mass into granules.

5. In a method for preparing granules of therapeutically active substances, the improvement which comprises the steps of moistening a dry, powdered mixtureof. a therapeutic agent, an excipient and an efiective amount up to and" including about 10%, by weight, of the resulting granules a member selected from the group consisting of talc, stearic acid, magnesium stearate and mixtures thereof with a solvent containing a binding agent, and forming the resulting mass'into granules.

6. In a method for preparinggranules of therapeutically active substances, the improvement which comprises the steps of moistening a dry, powdered mixture of a therapeutic compound, an excipient and an effective amount upto' a'nd includingabout 10%, by Weight, of the resulting granules, a member selected fro mthe group consisting of talc, stearic acid, magnesium stearate and mixturesthereof withan aqueous solvent containing a'mernber of the group consisting ofsucrose, gelatin, acacia and tragacanth and forming the resulting mass intov granules.

References Cited in the file of this patent UNITED STATES PATENTS Kupferbert et al. Feb. 21, 1956

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2735798 *Oct 21, 1952Feb 21, 1956 Acyl amevo-nitrothiazole compositions
US2736682 *Oct 11, 1954Feb 28, 1956Hermelin Victor MMethod of making a prolonged action medicinal tablet
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3033754 *Dec 21, 1959May 8, 1962Lakeside Lab IncTablets containing hydrazine derivatives
US3039927 *Oct 22, 1958Jun 19, 1962Lafon LouisPharmaceutical composition comprising aspirin and sorbitol
US3055433 *Aug 19, 1958Sep 25, 1962Ciba LtdEpoxy-resin enteric coated tablet and composition
US3096248 *Apr 6, 1959Jul 2, 1963Rexall Drug & Chemical CompanyMethod of making an encapsulated tablet
US4254099 *Oct 1, 1979Mar 3, 1981Beiersdorf AktiengesellschaftPharmaceutical tablet composition
US6080428 *Jan 4, 1995Jun 27, 2000Bova; David J.Nicotinic acid compositions for treating hyperlipidemia and related methods therefor
US6129930 *Mar 6, 1997Oct 10, 2000Bova; David J.Without causing treatment-limiting elevations in uric acid levels and/or glucose levels, by orally administering an antihyperlipidemic amount of niacin and an excipient to provide sustained release; fda orange book listed patent for niacin and simvastatin
US6676967Oct 31, 1997Jan 13, 2004Kos Pharmaceuticals, Inc.Methods for reducing flushing in individuals being treated with nicotinic acid for hyperlipidemia
US6746691Oct 31, 1997Jun 8, 2004Kos Pharmaceuticals, Inc.Intermediate release nicotinic acid formulation having a dissolution curve similarity fit factor of about 79, and in in vitro dissolution profile in deionized water at about 100rpm; time release agents; fda orange book listed patent for niacin and simvastatin
US6818229Oct 31, 1997Nov 16, 2004Kos Pharmaceuticals, Inc.Intermediate release nicotinic acid compositions for treating hyperlipidemia
US7385068Jun 16, 2005Jun 10, 2008Mallinckrodt Inc.Stearate composition and method
US7998506May 23, 2003Aug 16, 2011Kos Life Sciences, Inc.Dosing a hyperlipidemic with an effective anticholesterol amount of nicotinic acid once per day in the evening or at night; combined with a pharmaceutically acceptable carrier to form an oral solid dosage form; side effect reduction
US20100183715 *Jun 20, 2008Jul 22, 2010Bristo-Meyers Squibb CompanyTableted compositions containing atazanavir
US20130266648 *May 31, 2013Oct 10, 2013Bristol-Myers Squibb CompanyTableted compositions containing atazanavir
Classifications
U.S. Classification514/770, 514/784, 514/960
International ClassificationA61K9/20, A61K9/16
Cooperative ClassificationA61K9/16, Y10S514/96, A61K9/2095
European ClassificationA61K9/16, A61K9/20P