JP2002534373A - Composition containing hydroxypropylcellulose and anionic polymer, and its use as a pharmaceutical film coating - Google Patents

Abstract

  (57) [Summary] Use of a composition containing hydroxypropylcellulose and at least one anionic polymer such as sodium carboxymethylcellulose, and an aqueous solution of the composition for applying substances such as tablets, granules, beads and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

FIELD OF THE INVENTION [0001] The present invention relates to film-forming compositions, particularly compositions containing hydroxypropylcellulose and sodium carboxymethylcellulose.

BACKGROUND OF THE INVENTION [0002] The application of tablets, granules and beads with compositions that form polymer films is well known in the pharmaceutical industry. In addition to medical books, manuals and technical literature,
Patent publications in this field include U.S. Pat. No. 4,931,286, which includes sodium carboxymethylcellulose (SCMC) with a degree of substitution (DS) of 0.2-14 and a degree of polymerization (DP) of 150-400, and polyethylene glycol. High gloss pharmaceutical tablets containing the active ingredient in a binder matrix as a core with an outermost coating of (PEG) plasticizer are disclosed. The outermost coating is applied from an aqueous solution by spray application. This tablet has a much higher gloss than other cellulosic polymers. This eliminates the need to increase gloss with another coating. Also, because only very small amounts of sodium carboxymethylcellulose are required, it offers unexpected economic advantages in terms of raw material cost and processing time. In addition, sodium carboxymethylcellulose films dissolve much faster than films such as hydroxypropylmethylcellulose, so that they do not significantly interfere with the dissolution of the drug from the coated tablets.

[0003] Hydroxypropylcellulose has been used very successfully in aqueous film coatings to enhance the usefulness of hydroxypropylmethylcellulose.
[Hydroxypropyl methylcellulose (HP
Use of Klucel hydroxy-propylcellulose (HPC, National Pharmaceutical Collection (NF)) to enhance the utility of MC), Aqualon Technical Brutun VC-556A]. Hydroxypropyl methylcellulose has high tensile strength and very low elongation. The addition of high elongation Krusel HPC to a typical hydroxypropylmethylcellulose film coating results in very high film flexibility and substrate adhesion.

[0004] US Pat. No. 4,316,884 states that indoprofen can be used very safely in its effective anti-inflammatory administration to humans, and that the activity of indoprofen is based on the use of cellulose ethers such as ethyl cellulose. It is disclosed that inclusion of indoprofen microparticles in a solid protective coating can be very long.

SUMMARY OF THE INVENTION According to the present invention, hydroxypropylcellulose and at least one anionic polymer (eg, carboxymethyl ether salts of cellulose, methacrylic acid polymers and copolymers, carboxyvinyl polymers and copolymers, alginate, pectinin) Carboxylate, pectate, carrageenan, agar and polysaccharide). Also provided is a component comprising a substrate and a coating containing hydroxypropylcellulose and at least one anionic polymer.

[0006] Also provided is a method of coating a substrate, comprising (a) preparing an aqueous solution of hydroxypropyl cellulose and an anionic polymer, and (b) applying the solution to the substrate.

[0007] As used herein, the term "contains essentially" means that the specified ingredient is essential, but can also include other ingredients that do not prevent the advantages of the present invention from being obtained. I do.

DETAILED DESCRIPTION OF THE INVENTION Compositions of hydroxypropylcellulose and an anionic polymer (eg, sodium carboxymethylcellulose) have been found to have film forming properties. Films of this composition provide good gloss strength and elongation as well as high gloss film coatings.

[0009] Anionic polymers suitable for use in the present invention include carboxymethyl ether salts of cellulose (preferably SCMC), methacrylic acid polymers and copolymers, carboxyvinyl polymers and copolymers, alginates, pectinates, pectinates. Carboxylates of carrageenan, agar and polysaccharides.

[0010] Sodium carboxymethylcellulose suitable for use in the present invention has a degree of substitution (DS) of at least 0.2, preferably at least about 0.5. The degree of substitution of the sodium carboxymethylcellulose can be up to about 2.5, preferably up to about 0.9. The sodium carboxymethylcellulose has a degree of polymerization (DP) of at least about 100, preferably at least about 200. The degree of polymerization of sodium carboxymethylcellulose can be up to about 4,000, preferably up to about 1,000.

[0011] Hydroxypropyl cellulose suitable for the present invention has a weight average molecular weight of at least about 80,000. The molecular weight of hydroxypropyl cellulose can be up to about 1,150,000, preferably up to about 95,000.

The degree of substitution of carboxymethylcellulose sodium is indicated by the carboxymethyl group based on 3.0 as the total number of available androhexoic sites. Sodium carboxymethylcellulose is a cellulose gum available from Hercules, Inc. as Aqualon® SCMC. It meets all specifications of the United States Pharmacopeia as a free-flowing powder with a purity of 99.5%.

Hydroxypropylcellulose is a cellulose gum available from Hercules Inc. as Klucel® hydroxypropylcellulose. It meets all United States Pharmacopoeia specifications as a free-flowing powder.

[0014] The weight ratio of hydroxypropylcellulose to sodium carboxymethylcellulose is at least about 1:20, preferably at least about 1: 4. The weight ratio of hydroxypropylcellulose: sodium carboxymethylcellulose is
It may be up to about 20: 1, preferably up to about 4: 1.

[0015] Optionally, a plasticizer may be included in the composition of the present invention. Suitable plasticizers include ethanolamine, ethylene glycol, glycerol, 1,2,6-hexanetriol, mono-, di- and tri-acetin, 1,5-pentanediol, sorbitol, polyethylene glycol (weight average molecular weight of about 600 ), Propylene glycol and trimethylolpropane. A preferred plasticizer is propylene glycol, preferably having a molecular weight of about 400. If included,
The plasticizer is at least 1%, preferably at least about 5.5%, by weight of the total composition. Plasticizers, if included, can be up to about 50% by weight, preferably up to about 20% by weight, based on total composition weight.

The compositions of the present invention are particularly suitable for use as a coating on a substrate (eg, coating of tablets, granules, beads, etc.). One particular field of use is for coating pharmaceutical substrates (eg, tablets containing pharmaceutically active ingredients) or may be applied to novel pharmaceutical dosage forms. For this type of application, pharmaceutically-acceptable plasticizers such as polyethylene glycol can be used.

Other ingredients (active pharmaceutical ingredients, active cosmetic ingredients, nutritional supplements, coloring agents, opaque materials, surfactants, stabilizers, silica, silicone, preservatives, surface treatments,
Flavors, crosslinkers, and utility, value, and ease of preparation, or tablets, granules,
Beads and other polymers that are considered necessary and useful to facilitate the ease of application to other pharmaceutical dosage forms) can also be incorporated into the coating composition.

Representative active agents include antacids, anti-inflammatory substances (non-steroidal anti-inflammatory agents, NSAIDs, vasodilators, coronary vasodilators, cerebral venous vasodilators and peripheral vasodilators) But not limited to), anti-infectives, psychotropics, anti-manic drugs, stimulants, antihistamines, laxatives, decongestants, vitamins, gastrointestinal sedatives,
Antidiarrheal preparations, anxiolytics, antiarrhythmics, antihypertensives, vasoconstrictors and migraines, anticoagulants and antithrombotics, analgesics, antipyretics, hypnotics, sedatives, antiemetic, antiemetic Agents, anticonvulsants, neuromuscular preparations, hyperglycemic and hypoglycemic preparations, thyroid and antithyroid preparations, diuretics, antispasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic agents, ( Red blood cells) hematopoietic agents, antiasthmatics, expectorants, antitussives, mucopolysaccharide hydrolases, antiuricemia agents, and other preparations or substances that act locally in the mouth (
For example, local analgesics, local anesthetics, polypeptide agents, anti-HIV agents, chemotherapeutic agents, anti-neoplastic agents, etc.).

Examples of specific active agents include aluminum hydroxide, prednisolone, dexamethasone, aspirin, acetaminophen, ibuprofen, isosorbide dinitrate, nicotinic acid, tetracycline, ampicillin, dexabromopheniramine, chlorpheniramine, Albuterol pseudo-fedrine, loratadine theophylline, ascorbic acid, tocophenol, pyridoxine, metoclopramide,
Magnesium hydroxide, verapamil, procainamide hydrochloride, propranolol, captopril, ergotamine, flurazepam, diazepam, lithium carbonate,
Any active agent can be physically and chemically compatible with the blend of hydroxypropylcellulose and anionic polymer and other tablet ingredients, including insulin, furosemide, hydrochlorothiazide, guaifenesin, dextromethorphan and benzocaine.

Formulations containing NSAIDs (including acetaminophen in this application)
It may contain therapeutic amounts of other pharmaceutically active substances commonly used with NSAIDs, including other decongestants or bronchodilators (eg,
Pseudoephedrine, phenylpropanolamine, phenylephedrine and pharmaceutically acceptable salts thereof, antitussives (eg, caraminophen, dextromethorphan, and pharmaceutically acceptable salts thereof), antihistamines (eg, chlorpheniramine, Brompheniramine, dexchlorpheniramine,
Dexbrompheniramine, triprolidine, doxylamine, tripelenamine, cyproheptadine, pyrilamine, hydroxyzine, promethazine, azatazine and pharmaceutically acceptable salts thereof, non-sedating antihistamines (
For example, acrivastin, astemizole, cetirizine, ketotifen, loratidine, temerastin, terfenadine (US Pat. Nos. 4,254,129 and 4,285)
No. 957, the contents of which are incorporated herein), and pharmaceutically acceptable salts thereof), muscle relaxants such as glyceryl monoether SMR
Methcarbamol, mefenesin, mefenesin carbamate, cyclobenzapyrine, chlorzoxazone, mefenesic acid succinate, chlorphenesin carbamate, or a pharmaceutically acceptable salt thereof, and additives (eg, diphenhydramine, caffeine, Xanthine derivatives (US Pat. No. 4,558,051)
Include what is mentioned in the issue and insert the contents here. ) And pharmaceutically acceptable salts thereof), nutritional supplements, and combinations of any of the foregoing medicaments. The medicament may be combined with acetaminophen for the treatment of allergies, coughs, colds, cold-like and / or flu symptoms in mammals, including humans. However, these medicaments may be combined with acetaminophen as sleep aids (eg, diphenhydramine) or for other known purposes.

Anionic polymers (eg, sodium carboxymethylcellulose) crosslink in the presence of certain polyvalent cations. Sodium carboxymethylcellulose (SCMC) is an anionic water-soluble polymer. The chemical and physical properties of SCMC make it useful in a wide range of applications such as food, medicine and personal care. Treatment of aqueous SCMC with certain polyvalent salts causes their sedimentation. However, the sequential release of multivalent cations such as Al ³⁺ into SCMC solution
Via the carboxymethyl group leads to a uniform crosslinking of the polymer molecules. This allows
A gel is formed. The properties of the gel, as a result, depend on the amount of crosslinker involved, the concentration of polymer molecules and the DP (degree of polymerization). The rate at which gelation occurs depends on how quickly the Al ³⁺ ions are dissolved in the aqueous system. The final amount and gel time of the gel can be controlled by changing the degree and amount of viscosity of the SCMC used, the proportion of polyvalent cations and the pH of the medium.

Active ingredients that can be incorporated into coating compositions and into substrates (eg, tablets, granules, beads, etc.) include hypnotics, analgesics, antiepileptics, stimulants, psychotropics, neuromuscular blockade. Drugs, antispasmodics, antihistamines, antiallergic drugs, inotropic drugs, antiarrhythmic drugs, diuretics, antihypertensive drugs, vasoconstrictors, antitussive and expectorants, thyroid hormones, sex hormones, antidiabetic drugs, anticancer drugs, antibacterial drugs, chemotherapy It can be a pharmaceutically active ingredient, such as a therapeutic and a narcotic.

[0023] Coating compositions and substrates (eg, tablets, granules, beads, etc.) are cosmetically active formulations (eg, breath-cleaning compounds such as menthol, for oral hygiene, and like quaternary ammonium bases). And other flavors and fragrances commonly used for cleaning teeth and mouth. Flavoring effects can also be enhanced with flavor enhancers such as tartaric acid, citric acid, vanillin and the like.

The composition of the present invention is preferably applied from an aqueous solution for application of a substrate such as a tablet. A preferred method of applying a substrate with the composition of the present invention involves preparing an aqueous solution of hydroxypropylcellulose and an anionic polymer (eg, sodium carboxymethylcellulose) and applying the aqueous solution to the substrate. Optionally, the plasticizers described above can be included in the coating composition. When preparing aqueous solutions of sodium carboxymethylcellulose, hydroxypropylcellulose and a plasticizer, these aqueous solutions can be formulated together or separately. A suitable coating weight is at least about 0.5% by weight, more preferably at least about 0.75% by weight, based on the total weight of the substrate to be applied. The coating weight is about 10% by weight, based on the total weight of the substrate to be applied
And preferably up to about 2% by weight.

High gloss pharmaceutical tablets generally contain at least one pharmaceutically active ingredient in a binder matrix core with a coating of an anionic polymer (eg, sodium carboxymethylcellulose), hydroxypropylcellulose, and optionally a plasticizer. .

The compositions of the present invention have industrial utility in the manufacture of pharmaceutical formulations.

The following examples are provided for illustrative purposes only and do not limit the scope of the invention. All parts and percentages are by weight unless otherwise indicated.

Example 1 In this example, an air suspension column coater, Gratt GPCG5 / 9, obtained from Glatt Air Techniques was set up as follows.

[Table 1]

The tablets are fluidized by the action of air from a spray nozzle mounted in the center of the orifice plate at the bottom of the production chamber, through a cylindrical application partition. The tablets are applied with an aqueous solution as they pass through the spray. The area outside this partition is the lower floor. As the airflow in this area keeps the tablet almost weightless, the tablet can move quickly down and can be discharged horizontally into the gap at the bottom of the application partition.

While stirring, 24.8 g of sodium carboxymethylcellulose (obtained as Aqualon® 7L2PCMC from Hercules Inc.) and hydroxypropyl cellulose (Klucel® EF hydroxypropyl cellulose from Hercules Inc.) 24.8 g) were mixed with 906.5 g of deionized water. Mixing was continued until the solution became clear. Next, polyethylene glycol (Union Carbide (Union C
7.7 g) (obtained as PEG 400 from Arbide) was added to this solution and mixed until a homogeneous solution was obtained. The solution viscosities were measured to give values in the range of 125-300 cps to provide good application using a Glatt GPCG-5 coater.

The biconvex placebo tablet was transferred to a fluid bed and allowed to warm up for 5 minutes. next,
The coating solution was applied to the tablets. The weight increase was 1.9 (weight)%. The disintegration time of the tablet was 4:00 minutes. The gloss of the tablets was higher than that obtained with a hydroxypropylcellulose / hydroxypropylmethylcellulose coating. Gloss was measured with a multi-angle reflectometer ASTM D523-89.

[0032]

[Table 2]

EXAMPLE 2 24.8 g of Aqualon 7L2P sodium carboxymethylcellulose with stirring
Was added to 585.2 g of deionized water, and 24.8 g of Klucel EF hydroxypropylcellulose were mixed with 235.2 g of deionized water. Mixing was continued until the solution became clear. Next, 3.9 g of polyethylene glycol (obtained as PEG 400 from Union Carbide) was added to both of these solutions and mixed until a homogeneous solution was obtained. 3.1 g of aluminum chloride was dissolved in 50 g of deionized water. This solution was added to the hydroxypropylcellulose solution and mixed until a homogeneous solution was obtained. Solution viscosities were measured and values ranging from 125 to 175 cps were obtained to provide good application using a Glatt GPCG-5 coater. These solutions were transferred to a fluid bed and allowed to warm up for 5 minutes. Spray application was started with a layer of sodium carboxymethylcellulose and then sprayed with a layer of hydroxypropylcellulose.
These layers were alternated and the final layer was sodium carboxymethylcellulose. The weight increase was 1.7 (weight)%. The disintegration time of this layered tablet was 8:10 minutes.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 9/50 A61K 9/50 47/10 47/10 47/32 47/32 47/34 47/34 47 / 36 47/36 C08L 1/10 C08L 1/10 101/02 101/02 (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH) , GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE , KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, UZ, VN, YU, ZA, ZW (72) Inventor Weldin W. Harkham Newark, Delaware, United States 19713, USA West Cherokee Drive No. 77 (72) Inventor George W. Skinner United States 19809 Delaware, Wilmington, Rd. 1503 Ridge Road F-term (reference) 4C076 AA44 AA64 CC01 CC11 CC15 CC21 CC27 C C30 CC31 CC40 EE09H EE11H EE30H EE32H EE36H EE48H FF27 4C083 AC111 AC121 AC131 AC541 AD041 AD091 AD211 AD281 AD301 AD351 CC01 DD15 DD16 EE03 4J002 AB02W AB03X AB05X BG05X CH02Y CH05Y EC046 EC0456 FD04 GB04

Claims (81)

[Claims] Claims: 1. A composition for providing a high gloss coating essentially comprising hydroxypropylcellulose and at least one anionic polymer. 2. The method of claim 1, wherein the anionic polymer is a carboxymethyl ether salt of cellulose, methacrylic acid polymers and copolymers, carboxyvinyl polymers and copolymers, alginates, pectinates, pectates, carrageenans,
The composition of claim 1, wherein the composition is selected from the group consisting of agar and a carboxylate of a polysaccharide. 3. The composition according to claim 2, wherein the anionic polymer is selected from the group consisting of carboxymethyl ether salts of cellulose. 4. The composition according to claim 3, wherein the carboxymethyl ether salt of cellulose is carboxymethyl cellulose sodium. 5. The composition of claim 4, wherein the degree of substitution of sodium carboxymethylcellulose is at least about 0.2. 6. The composition according to claim 4, wherein the degree of substitution of sodium carboxymethylcellulose is up to about 2.5. 7. The composition of claim 4, wherein the degree of polymerization of sodium carboxymethylcellulose is at least about 100. 8. The polymerization degree of sodium carboxymethylcellulose is about 4,000.
5. The composition according to claim 4, wherein 9. The hydroxypropyl cellulose having a molecular weight of at least about 80,0.
The composition according to claim 2, which is 00. 10. The composition according to claim 2, wherein the molecular weight of the hydroxypropyl cellulose is up to about 1,150,000. 11. The composition according to claim 2, further comprising a plasticizer. 12. The composition of claim 4, wherein the weight ratio of hydroxypropylcellulose to sodium carboxymethylcellulose is at least about 1:20. 13. The composition of claim 4, wherein the weight ratio of hydroxypropylcellulose to sodium carboxymethylcellulose is up to about 20: 1. 14. The composition of claim 11, wherein the amount of plasticizer is at least about 1% by weight, based on the total composition weight. 15. The composition of claim 11, wherein the amount of plasticizer is up to about 50% by weight, based on the total composition weight. 16. The composition according to claim 2, comprising at least one additive selected from the group consisting of a crosslinking agent, a pharmaceutically active ingredient, a cosmetic active ingredient and a nutritional supplement. 17. The method according to claim 17, wherein the sodium carboxymethylcellulose has a substitution degree of about 0.2.
About 2.5 and a degree of polymerization of about 100 to about 4,000, the hydroxypropyl cellulose has a weight average molecular weight of about 80,000 to about 1,150,000, and the weight ratio of hydroxypropyl cellulose: sodium carboxymethyl cellulose is about 1:20 to about The composition of claim 4, wherein the composition comprises 20: 1 and optionally an additive selected from the group consisting of a plasticizer, a crosslinker, a pharmaceutically active ingredient, a cosmetic active ingredient and a nutritional supplement. 18. The composition of claim 17, wherein the degree of substitution of sodium carboxymethylcellulose is at least about 0.5. 19. The method according to claim 19, wherein the substitution degree of sodium carboxymethylcellulose is about 0.9.
18. The composition of claim 17, wherein 20. The composition of claim 17, wherein the degree of polymerization of sodium carboxymethylcellulose is at least about 200. 21. The polymerization degree of sodium carboxymethylcellulose is about 1,00.
18. The composition of claim 17, wherein the value is up to zero. 22. The hydroxypropyl cellulose having a molecular weight of at least about 80
18. The composition of claim 17, wherein the composition is 10,000. 23. The composition according to claim 17, wherein the molecular weight of the hydroxypropyl cellulose is up to about 95,000. 24. Polyethylene glycol ethanolamine, ethylene glycol, glycerol, 1,2,6-hexanetriol, mono-, di- and tri-acetin, 1,5-pentanediol, sorbitol, polyethylene glycol, propylene and glycol triol 18. The composition according to claim 17, comprising a plasticizer selected from the group consisting of methylolpropane. 25. The composition of claim 17, wherein the weight ratio of hydroxypropylcellulose to sodium carboxymethylcellulose is at least about 1: 4. 26. The composition of claim 17, wherein the weight ratio of hydroxypropylcellulose: sodium carboxymethylcellulose is up to about 4: 1. 27. The amount of plasticizer is at least about 5.5 parts by weight of the total composition.
18. The composition of claim 17, which is in weight percent. 28. The composition of claim 17, wherein the amount of plasticizer is up to about 20% by weight, based on the total composition weight. 29. The sodium carboxymethyl cellulose having a degree of substitution of about 0.5
Having a weight average molecular weight of about 80,000 to about 95,000, wherein hydroxypropyl cellulose has a weight average molecular weight of about 80,000 to about 95,000;
The weight ratio of sodium carboxymethylcellulose is from about 1: 4 to about 4: 1, and optionally, a crosslinking agent, a pharmaceutically active ingredient, a cosmetically active ingredient, a nutritional supplement and ethanolamine, ethylene glycol, glycerol, 1,2, Addition selected from the group consisting of 6-hexanetriol, mono-, di- and tri-acetin, 1,5-pentanediol, sorbitol, polyethylene glycol, propylene and a plasticizer selected from the group consisting of glycol trimethylolpropane 18. The composition according to claim 17, comprising a substance. 30. The composition according to claim 17, wherein the plasticizer is polyethylene glycol. 31. The polyethylene glycol having a molecular weight of about 400.
9. The composition according to 8. 32. A component comprising a substrate and a coating comprising the composition of claim 1. 33. An article comprising a substrate and a coating comprising the composition of claim 2. 34. A component comprising a substrate and a coating comprising the composition of claim 4. 35. A component comprising a substrate and a coating comprising the composition of claim 17. 36. An article comprising a substrate and a coating comprising the composition of claim 29. 37. The composition according to claim 32, wherein the substrate contains a pharmaceutically active ingredient. 38. The composition according to claim 33, wherein the substrate contains a pharmaceutically active ingredient. 39. The composition according to claim 34, wherein the substrate contains a pharmaceutically active ingredient. 40. The composition according to claim 35, wherein the substrate contains a pharmaceutically active ingredient. 41. The composition according to claim 36, wherein the substrate contains a pharmaceutically active ingredient. 42. The pharmaceutically active ingredient is a hypnotic, analgesic, antiepileptic, stimulant, psychotropic, neuromuscular blocker, antispasmodic, antihistamine, antiallergic, inotropic, antiarrhythmic, diuretic. 33. The component of claim 32, wherein the component is selected from the group consisting of agents, antihypertensives, vasoconstrictors, antitussives and expectorants, thyroid hormones, sex hormones, antidiabetic agents, anticancer agents, antibacterial agents, chemotherapeutic agents and narcotics. 43. The pharmaceutically active ingredient is a hypnotic, an analgesic, an antiepileptic, a stimulant, a psychotropic, a neuromuscular blocker, an antispasmodic, an antihistamine, an antiallergic, an inotropic, an antiarrhythmic, a diuretic. 34. The component of claim 33 selected from the group consisting of agents, antihypertensives, vasoconstrictors, antitussives and expectorants, thyroid hormones, sex hormones, antidiabetic agents, anticancer agents, antibacterial agents, chemotherapeutic agents and narcotics. 44. The pharmaceutically active ingredient is a hypnotic, an analgesic, an antiepileptic, a stimulant, a psychotropic, a neuromuscular blocker, an antispasmodic, an antihistamine, an antiallergic, an inotropic, an antiarrhythmic, a diuresis. 35. The component of claim 34, wherein the component is selected from the group consisting of agents, antihypertensives, vasoconstrictors, antitussives and expectorants, thyroid hormones, sex hormones, antidiabetic agents, anticancer agents, antibacterial agents, chemotherapeutic agents and narcotics. 45. The pharmaceutically active ingredient is a hypnotic, an analgesic, an antiepileptic, a stimulant, a psychotropic, a neuromuscular blocker, an antispasmodic, an antihistamine, an antiallergic, an inotropic, an antiarrhythmic, a diuresis. 36. The component of claim 35, wherein the component is selected from the group consisting of agents, antihypertensives, vasoconstrictors, antitussives and expectorants, thyroid hormones, sex hormones, antidiabetic agents, anticancer agents, antibacterial agents, chemotherapeutic agents and narcotics. 46. The pharmaceutically active ingredient is a hypnotic, analgesic, antiepileptic, stimulant, psychotropic, neuromuscular blocker, antispasmodic, antihistamine, antiallergic, inotropic, antiarrhythmic, diuretic. 37. The component of claim 36 selected from the group consisting of agents, antihypertensives, vasoconstrictors, antitussives and expectorants, thyroid hormones, sex hormones, antidiabetic agents, anticancer agents, antibacterial agents, chemotherapeutic agents and narcotics. 47. The composition of claim 32, wherein the substrate contains a cosmetically active ingredient. 48. The composition according to claim 34, wherein the substrate contains a cosmetically active ingredient. 49. The substrate is selected from the group consisting of breath-cleansing compounds, other flavors and flavors commonly used for oral hygiene and for cleaning teeth and mouth, tartaric acid, citric acid and vanillin. 35. The composition of claim 34, comprising a cosmetically active ingredient. 50. The composition of claim 32, wherein said substrate comprises a nutritional supplement. 51. The composition of claim 34, wherein said substrate comprises a nutritional supplement. 52. The component of claim 32, wherein the coating comprises at least one additive selected from the group consisting of a crosslinker, a pharmaceutically active ingredient, a cosmetic active ingredient, and a nutritional supplement. 53. The composition of claim 33, wherein the coating comprises at least one additive selected from the group consisting of a crosslinking agent, a pharmaceutically active ingredient, a cosmetic active ingredient, and a nutritional supplement. 54. The component of claim 34, wherein the coating comprises at least one additive selected from the group consisting of a crosslinking agent, a pharmaceutically active ingredient, a cosmetic active ingredient, and a nutritional supplement. 55. The composition of claim 35, wherein the coating comprises at least one additive selected from the group consisting of a crosslinking agent, a pharmaceutically active ingredient, a cosmetic active ingredient, and a nutritional supplement. 56. The composition of claim 36, wherein the coating comprises at least one additive selected from the group consisting of a crosslinking agent, a pharmaceutically active ingredient, a cosmetic active ingredient, and a nutritional supplement. 57. A method of applying a substrate, comprising: (a) preparing an aqueous solution of the composition of claim 1, and (b) applying the solution to the substrate. 58. A method of applying a substrate, comprising: (a) preparing an aqueous solution of the composition of claim 2, and (b) applying the solution to the substrate. 59. A method of applying a substrate, comprising: (a) preparing an aqueous solution of the composition of claim 4, and (b) applying the solution to the substrate. 60. A method of applying a substrate, comprising: (a) preparing an aqueous solution of the composition of claim 17, and (b) applying the solution to the substrate. 61. A method of applying a substrate, comprising: (a) preparing an aqueous solution of the composition of claim 29; and (b) applying the solution to the substrate. 62. The method of claim 57, wherein the shape of the substrate is selected from the group consisting of tablets, granules, and beads. 63. The method of claim 58, wherein the shape of the substrate is selected from the group consisting of tablets, granules and beads. 64. The method according to claim 59, wherein the shape of the substrate is selected from the group consisting of tablets, granules and beads. 65. The method of claim 60, wherein the shape of the substrate is selected from the group consisting of tablets, granules and beads. 66. The aqueous solution comprises an active pharmaceutical ingredient, a crosslinking agent, a pigment, an antioxidant,
Consists of colorants, opaque materials, surfactants, stabilizers, silica, silicone, preservatives, surface treatments, fragrances, cosmetically active ingredients, nutritional supplements, and other polymers that impart the desired characteristics to the substrate being coated 64. The method according to claim 63, comprising at least one additive selected from the group. 67. The aqueous solution comprises an active pharmaceutical ingredient, a crosslinking agent, a pigment, an antioxidant,
Consists of colorants, opaque materials, surfactants, stabilizers, silica, silicone, preservatives, surface treatments, fragrances, cosmetically active ingredients, nutritional supplements, and other polymers that impart the desired characteristics to the substrate being coated 65. The method of claim 64, comprising at least one additive selected from the group. 68. The method according to claim 66, wherein the additive is selected from the group consisting of multivalent ionic salts. 69. The method of claim 67, wherein said additive is selected from the group consisting of multivalent ionic salts. 70. The method of claim 69, wherein said polyvalent ionic salt is selected from the group consisting of aluminum, calcium, magnesium, iron, zinc, titanium and zirconium salts. 71. The method of claim 69, wherein the polyvalent ionic salt is selected from the group consisting of an aluminum salt and a calcium salt. 72. An aqueous solution of hydroxypropylcellulose and sodium carboxymethylcellulose is prepared separately, and the aqueous solution of hydroxypropylcellulose is an active pharmaceutical ingredient, a crosslinker, a pigment, an antioxidant, a colorant, an opaque material, an interface. Additives selected from the group consisting of activators, stabilizers, silicas, silicones, preservatives, surface treatments, fragrances, cosmetically active ingredients, nutritional supplements, and other polymers that impart the desired characteristics to the substrate being coated. 51. The method of claim 50 containing at least one. 73. The method of claim 72, wherein the additive is selected from the group consisting of multivalent ionic salts. 74. The method of claim 73, wherein the polyvalent ionic salt is selected from the group consisting of aluminum, calcium, magnesium, iron, zinc, titanium and zirconium salts. 75. The method of claim 74, wherein the polyvalent ionic salt is selected from the group consisting of an aluminum salt and a calcium salt. 76. The component of claim 32, wherein the coating comprises at least about 0.5% by weight of the total weight of the component. 77. The component of claim 34, wherein the coating comprises at least about 0.5% by weight of the total weight of the component. 78. The component of claim 32, wherein the coating comprises up to about 10% by weight of the total weight of the component. 79. The component of claim 34, wherein the coating comprises up to about 10% by weight of the total weight of the component. 80. The component of claim 35, wherein the coating comprises at least about 0.75% by weight of the total weight of the component. 81. The component of claim 35, wherein the coating comprises up to about 2% by weight of the total weight of the component.