IL28931A - Delayed release medicinal tablet - Google Patents
Delayed release medicinal tabletInfo
- Publication number
- IL28931A IL28931A IL28931A IL2893167A IL28931A IL 28931 A IL28931 A IL 28931A IL 28931 A IL28931 A IL 28931A IL 2893167 A IL2893167 A IL 2893167A IL 28931 A IL28931 A IL 28931A
- Authority
- IL
- Israel
- Prior art keywords
- tablet
- medicine
- wax
- temperature
- wax additive
- Prior art date
Links
- 230000003111 delayed effect Effects 0.000 title description 3
- 239000003814 drug Substances 0.000 claims description 38
- 239000000654 additive Substances 0.000 claims description 25
- 239000001993 wax Substances 0.000 claims description 22
- 230000000996 additive effect Effects 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 16
- 239000011248 coating agent Substances 0.000 claims description 14
- 238000000576 coating method Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- 239000000155 melt Substances 0.000 claims description 7
- 238000002844 melting Methods 0.000 claims description 7
- 230000008018 melting Effects 0.000 claims description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 230000002411 adverse Effects 0.000 claims description 4
- 235000013871 bee wax Nutrition 0.000 claims description 4
- 239000012166 beeswax Substances 0.000 claims description 4
- 229960000541 cetyl alcohol Drugs 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 239000003925 fat Substances 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- WCOXQTXVACYMLM-UHFFFAOYSA-N 2,3-bis(12-hydroxyoctadecanoyloxy)propyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC(O)CCCCCC)COC(=O)CCCCCCCCCCC(O)CCCCCC WCOXQTXVACYMLM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 229920013820 alkyl cellulose Polymers 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- 150000002191 fatty alcohols Chemical class 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 3
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000003921 oil Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 2
- 239000000194 fatty acid Substances 0.000 claims 2
- 229930195729 fatty acid Natural products 0.000 claims 2
- 150000004665 fatty acids Chemical class 0.000 claims 2
- 230000002496 gastric effect Effects 0.000 claims 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 2
- 239000011707 mineral Substances 0.000 claims 2
- 239000004698 Polyethylene Substances 0.000 claims 1
- 235000011187 glycerol Nutrition 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 229920000573 polyethylene Polymers 0.000 claims 1
- 235000013311 vegetables Nutrition 0.000 claims 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 6
- 239000001103 potassium chloride Substances 0.000 description 4
- 235000011164 potassium chloride Nutrition 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 238000005054 agglomeration Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229940097982 chlorothiazide 500 mg Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- -1 hydroxypropyl Chemical group 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000006223 plastic coating Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
Description
rgniiui H jr TJinrm PATENT ATTORNEYS ·' LVD -D E) 'DUIJ PATENTS AND DESIGNS ORDINANCE SPECIFICATION delayed Release Medicinal Tablet I/We MERCK & CO., INC., a corporation of Hew Jersey, U.S.A. , of Rahway, Hew Jersey, U.S.A. do hereby declare the nature of this invention and in what manner the same is to be performed, to be particularly described and ascertained in and by the following statement :— This invention relates to pharmaceutical compositions and particularly to tablet preparations which upon ingestion are capable of prolonging the release of the contained medicine or drug over extended periods of time.
This invention also involves a process for making these pharmaceutical tablets.
This prolonged or sustained release of a medicine or drug is important for several reasons. In the first place it serves to provide the body with medication over a long time and thereby eliminates the need for swallowing an ordinary tablet at frequent; intervals. The treatment of any disease with a medicine requires a fairly constant high body titre of the medicine. If the medicine is metabolized, or otherwise eliminated quickly from the body it would be necessary to swallow an ordinary tablet quite o ten to maintain the desired therapeutic level. The sustained re-, lease tablet of this invention makes it possible to swallow the tablet at considerably less frequent intervals.
Some medicines have such a narrow therapeutic ratio that slightly more of it than is necessary to achieve a therapeutic effect, will cause adverse toxic symptoms. If an ordinary tablet is taken, the rapid release of its medical content may cause such a high body level that undesirable side reactions will occur. The prolonged release tablet of this invention prevents the sudden release of a large amount of medicine and thereby prevents the onset of toxic symptoms.
Some medicines are inherently irritating to the alimentary mucosa and their rapid release f om the ordinary ; tablet may cause damage at the loci of high concentrations Tablets have -rcn prepared in the past which will prolong the release οί' the icontained medicine but they have not been entirely satisfactory. Some of them have been too expensive to make either because of the expensive ingredients or the complicated apparatus or process to make them or they have been too large because of the necessary additives to obtain the delayed release. Other tablets have been unsatisfactory because they have poorly reproducible release patterns although made in exactly the same way. The tablets of the present invention employ inexpensive tableting material and achieve an exceptionally uniform release of the medicine. These tablets can be made of relatively small size. Furthermore, the total elapsed drug release time can be varied and established by the practice of this invention.
Another important consideration is that the material which causes the prolonged drug release must be physiologically acceptable. It must have no or a negligible toxic effect upon the person. It must be completely eliminated so that even during prolonged use it does not accumulate in the person's tissues.
In accordance with the invention, the drug is mixed with a suitable wax or wax-like substance which will melt at a temperature at which the drug will not decompose or be otherwise adversely affected. This wax or wax-like substance is hereinafter called the wax additive and preferred ones are cetyl alcohol, castor wax, glycerol monostearate, stearyl alcohol, stearic acid, beeswax and solid polyethylene glycols. Lubricants and/or flow conditioners which are conventional in the tablet art may or may not be added with further inter- \ t The tablets are coated with a suitable film forming material, such as methylcellulose, which is not affected either by the molten wax or by the elevated temperature at which the wax melts. This coating material should not be-come tacky during the subsequent heating procedure so as to thereby prevent agglomeration of the tablets. The coated tablets are placed for a predetermined period in a drying oven set at a temperature higher than the melting point of the wax additive. This heating causes the wax additive to soften or melt and the coating serves to preserve the shape of the tablet and to prevent agglomeration of tablets. After cooling to room temperature the tablets exhibit the desired sustained release effect.
The mechanism involved in producing the sustained release property is that 'the drug particles are coated during the melting operation with a continuous film of the waxr additive. When the compressed, coated tablets are exposed to an elevated temperature* the additive melts and flows between the drug particles. This step in the process serves the additional function of driving off residual solvents from the film coat. Upon cooling to room temperature, the wax additive solidifies to form a continuous structure in which drug particles are imbedded. Upon ingestion, the wax additive is slowly dissolved or disintegrated, resulting in the availability of the drug at a controlled rate.
The wax-additives which may be employed in the practice of this invention should have melting points above body temperature and should be slowly soluble or disintegrat-able by digestion in g£- str-o-intestinal fluids. Among them as animal fats and hardened vegetable oils, Including hydro genated fats and oils; higher fatty alcohols and acids such as octyl, decyl, lauryl, myristyl, cetyl or stearyl.
The coating v.'hich is applied directly to the wax-additive core, in addition to the methylcellulose mentioned above, may be ethylcellulose, cellulose acetate, cellulose acetate phthalate or a substituted alkyl cellulose such as hydroxypropyl methylcellulo'se . Other conventional coatings-may be used if it is known that it will not melt or become sticky during the heating step which melts the waxy core. Sufficient coating should be applied so that it will serve to retain the shape and also prevent agglomeration of the tablets during the time that the core is molten, and for this purpose the film should be from .03 to 0.1 mm. thick.
The heating temperature should be slightly above the predetermined melting temperature of the wax additive and it should be sustained for a period that will assure the melting of the entire wax additive. This will generally require a minimum of about 30 minutes although the tablets may be heated for as long as an overnight period.
The amount of weight of the wax additive should be from 5$ to 95 and preferably from 10 to 20$ of the weight of the drug. Amounts higher than 25$ generally will be used when a mixture of additives is required for special release effects such as a release spread over an entire day or more.
The release time of the drug will be dependent upon the part cular selected wax additive and the particle size of the dru The process of this invention is an economical one These coated, cooled tablets can be swallowed in the form in v/hich they come from the heating step and consequently they may be sold as the final end use product.
However, their appearance, taste and ability to stand ship- 5 ment and shelf age, may make it desirable to further coat them. This overcoating may be a conventional sugar or plastic coating which is applied in a tumbling pan or by a spray using known materiels, the spray being directed upon the tumbling tablets in a pan or upwardly into a fluidized column of tablets. These are known techniques and form no part of this invention as the feature of this concept is the core of such a coated tablet.
A medicament may be added to the coating next to j the wax core if the medicament will withstand the heating 1 15 step. This may be utilized if this medicament is chemically incompatible with the medicament in the core, or if it is I desired that the medicament in the coating be quickly released.
For example, the coating may contain a diuretic such as hydrochlorothiazide so as to quickly get it into the person's 1 20 system and the core may contain potassium chloride so that it will be released slowly. The overcoating may, as well, contain a medicament, for the same reasons.
The invention is illustrated by the following examples : EXAMPLE 1 Ingredients per core tablet: Potassium chloride (Granular) 1,000 mg.
Cetyl alcohol 150 mg.
Procedure : The ingredients are thoroughly intermixed and , com ressed to form tablets containin the desired wei ht , A coating solution of the following composition prepared: Hydroxypropylmethylcellulose.
Alcohol Chloroform The film coating is applied to the tablets by a continuous spraying operation v/ell knov/n to those in the industry. Thirty milligrams of coating are applied to each tablet. The tablets are then placed in an oven (110° C) for 30 minutes. The finished product is obtained by cooling the tablets to room temperature. The dissolution time of the resulting tablet in water (75 ml.) was as follo\ EXAMPLE 3 Ingredients per core tablet: Potassium chloride (Granular) 1,000 mg.
Castor wax 150 mg.
Stearic acid 5 mg.
The procedure described in Example 1 is followed.
EXAMPLE k Ingredient per core tablet: Amitriptyline 0; mg.
The procedure of Example 1 is followed, and the dissolution rate of the resulting tablet in water { 750 ml.) is as follows: Time (hours)- 1 2 3 4 5 6 7 co Dissolved 31.8 44.6 52 .0 58.5 63.2 69.0 72.5 Time (hours) 8 9 10 11 12 13 Dissolved 76.0 79.5 82 . 85.5 88.0 90.1 EXAMPLE 5 Any one of the preceding examples is carried out but 5 mg. of anhydrous colloidal silica is added per tablet.
Other examples are apparent from the above specific, illustrative ones. Any one of the wax-additives mentioned above may be substituted for those in the above examples and they may be added within the 5 to 9 i^ range which has been mentioned. The medicament may be substances other than potassium chloride, such as is represented by the following: EXAMPLE 6 Ingredients per core tablet: Chlorothiazide 500 mg.
Cetyl alcohol 75 mg.
The procedure of Example 1 is carried out. Also, other examples are evident, considering that for the hydroxy-propylmethylcellulose coating may be substituted other known
Claims (7)
1. C L A I H S:
2. , A medicine tablet which will prolong the release of the contained medicine ¾Mch comprises drug particles contained in the cooled melt of a wax additive which is solid at room temperature but which melts at a temperature at which the medicine will note be affected adversely and which is slowly fluids dissolved in or is slowly disintegrated by gastric/ and a coating which will preserve its shape at the temperature at which the wax additive melts. ί?. A tablet according to claim 1 in which the wax additive is selected from the group consisting of hardened organic animal, yegetable and mineral fats and oils, higher fatty alcohols, higher fatty acids, beeswax, glycerol monostearate and solid polyethylene glycol,
3. » A tablet according to claim 1 in which the wa additive is selected fronr the group consisting of cetyl alcohol, castor wax, glycerol monostearate, stearyl alcohol, stearic acid, beeswax and solid polyethylene glycol.
4. A tablet accordin to claim 1 in which said coating is selected from the group consisting^methylcellulose, ethylcellulose and a substituted alkylcellulose.
5. The method of making a medicine tablet which will' rolong the release, of the contained medicine which comprises mixing together medicine particles and a wax additive which is solid at room temperature but which melts at a temperature at which the medicine will not be affected adversely and which is slowly dissolved in or is slowly disintegrated by gastric fluids, compressing the mixture into tablet form to make a tablet core, coating the core with a material which will retain its shape at the temperature at which the wax additive melts, heating the coated core to at least the melting temperature of the wax additive for a period to assure the melting of the wax additive, and cooling the tablet to room temperature.
6. The process according to claim 5 in which the wax additive is selected from the group consisting of . ·■ ' hardened, organic animal, vegetable and mineral fats and oils, higher fatty alcohols, higher fatty acids, beeswax, glycerol solid rnonostearate and/polyethylene χίά&τ glycol.
7. The process according to claim 5 in which coating the wa¾-¾-dri4 Ate is selected from the group consisting of methylcellulose, ethylcellulose and a substituted alkyl-cellulose .
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59645866A | 1966-11-23 | 1966-11-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL28931A true IL28931A (en) | 1971-07-28 |
Family
ID=24387352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL28931A IL28931A (en) | 1966-11-23 | 1967-11-13 | Delayed release medicinal tablet |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US3487138A (en) |
| DE (1) | DE1617657A1 (en) |
| FR (1) | FR1561127A (en) |
| GB (1) | GB1179938A (en) |
| IL (1) | IL28931A (en) |
| NL (1) | NL6715224A (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4137300A (en) * | 1976-08-20 | 1979-01-30 | Ciba-Geigy Corporation | Sustained action dosage forms |
| GB1598458A (en) * | 1977-04-01 | 1981-09-23 | Hoechst Uk Ltd | Tableting of microcapsules |
| DE3024416C2 (en) * | 1980-06-28 | 1982-04-15 | Gödecke AG, 1000 Berlin | Process for the production of medicaments with sustained release of active substances |
| JPS57171428A (en) * | 1981-04-13 | 1982-10-22 | Sankyo Co Ltd | Preparation of coated solid preparation |
| FR2548021B1 (en) * | 1983-06-29 | 1986-02-28 | Dick P R | PROLONGED AND CONTINUOUS DERMAL PHARMACEUTICAL COMPOSITIONS BASED ON ESSENTIAL FATTY ACIDS |
| GB2170104A (en) * | 1985-01-30 | 1986-07-30 | Warner Lambert Co | Coated pharmaceutical dosage forms |
| US4657784A (en) * | 1986-03-10 | 1987-04-14 | Ecolab Inc. | Process for encapsulating particles with at least two coating layers having different melting points |
| IT1204294B (en) * | 1986-03-11 | 1989-03-01 | Gentili Ist Spa | METHOD OF MANUFACTURE OF GRANULARS SUITABLE FOR THE PRODUCTION OF COATED TABLETS, FOR ORAL USE, WITH CONTROLLED RELEASE |
| JP2681373B2 (en) * | 1988-07-18 | 1997-11-26 | 塩野義製薬株式会社 | Method for manufacturing sustained-release preparation |
| JPH03232814A (en) * | 1990-02-08 | 1991-10-16 | Shin Etsu Chem Co Ltd | Method for manufacturing sustained release tablets |
| US5714167A (en) * | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| AU8913491A (en) * | 1990-11-30 | 1992-06-25 | Yamanouchi Pharmaceutical Co., Ltd. | Quick release coated preparation |
| ES2096103T3 (en) * | 1992-01-13 | 1997-03-01 | Pfizer | PREPARATION OF INCREASED RESISTANCE TABLETS. |
| DE69332291T2 (en) * | 1992-10-16 | 2003-07-31 | Nippon Shinyaku Co., Ltd. | METHOD FOR PRODUCING WAX MATRICES |
| US5690959A (en) * | 1993-05-29 | 1997-11-25 | Smithkline Beecham Corporation | Pharmaceutical thermal infusion process |
| US5827537A (en) * | 1995-05-04 | 1998-10-27 | Smithkline Beecham Corporation | Pharmaceutical thermal infusion process |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2987445A (en) * | 1958-10-10 | 1961-06-06 | Rohm & Haas | Drug composition |
| US3308217A (en) * | 1965-02-09 | 1967-03-07 | Lowy Lawrence | Method of granulating materials for subsequent forming into tablets |
| US3400185A (en) * | 1965-04-08 | 1968-09-03 | Bristol Myers Co | Agglomeration of smaller pharmaceutical particles into larger microspherules and enteic-coating thereof |
-
1966
- 1966-11-23 US US596458A patent/US3487138A/en not_active Expired - Lifetime
-
1967
- 1967-11-09 NL NL6715224A patent/NL6715224A/xx unknown
- 1967-11-13 IL IL28931A patent/IL28931A/en unknown
- 1967-11-13 FR FR1561127D patent/FR1561127A/fr not_active Expired
- 1967-11-20 GB GB52706/67A patent/GB1179938A/en not_active Expired
- 1967-11-21 DE DE19671617657 patent/DE1617657A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| FR1561127A (en) | 1969-03-28 |
| DE1617657A1 (en) | 1971-09-02 |
| GB1179938A (en) | 1970-02-04 |
| US3487138A (en) | 1969-12-30 |
| NL6715224A (en) | 1968-05-24 |
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