CA1063023A - Particulate compositions for ointment preparation - Google Patents
Particulate compositions for ointment preparationInfo
- Publication number
- CA1063023A CA1063023A CA251,156A CA251156A CA1063023A CA 1063023 A CA1063023 A CA 1063023A CA 251156 A CA251156 A CA 251156A CA 1063023 A CA1063023 A CA 1063023A
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- CA
- Canada
- Prior art keywords
- parts
- composition according
- group
- water
- alkaline substance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
- A61K8/022—Powders; Compacted Powders
- A61K8/0225—Granulated powders
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Abstract
PARTICULATE COMPOSITIONS
FOR OINTMENT PREPARATION
Abstract A particulate solid composition from which an ointment can be rapidly prepared comprises an anionic crosslinked high molecular weight carboxyvinyl polymer and admixed with an alkaline substance. Either or both of the polymer and the alkaline substance is coated with one or more emulsifiers and/or lipophilic vehicle substances.
FOR OINTMENT PREPARATION
Abstract A particulate solid composition from which an ointment can be rapidly prepared comprises an anionic crosslinked high molecular weight carboxyvinyl polymer and admixed with an alkaline substance. Either or both of the polymer and the alkaline substance is coated with one or more emulsifiers and/or lipophilic vehicle substances.
Description
~063r~z3 Detai]ed D~scription Pharmaceutical formulations intended for local application, either therapeutically or cosmetically, to healthy, in~ured or diseased skin or to mucous membranes can be broadly grouped under the term "ointment". These formulations are gels which can undergo plastic deformation and which change their shape even under slight mechanical stress due to pressure, shearing, rubbing or spreading and adapt to the walls of the body cavities or to the shape of the skin surfaces onto which they are applied. Their gel nature im~arts to them dimensional stability, both when stored in containers and at the point of application.
Among these ointments, hydrogels and emulsion ointments of the "oil-in-later" type rsee M~nzel, Versuch einer 3y~ema~ik der Saiben nacn gaieniscnen ~esicntspunkten Pharm. Acta Helv. 28, 320 (1953)J occupy a special position inasmuch as they can be easily washed off with water. Recause of their high water content they can be rubbed onto the skin easily with good penetration and, due to the evaporation of water, produce a pleasant cooling effect.
The emulsion ointments are generally prepared by machine. For example a typical procedure involves melting the fat phase, adding the required amount of hot water and the:l emulsifying the two phases with vigorous stirring, fre-quently with the aid of emulsifier~ and emulsion stabilizers such as thickeners or swelling agents. These latter com-~k `~
- 1 - ~
. .
- . .
-- ~ - ., .
1063~1Z3 ponents are intended to prevent subsequent separation of the emulsion. After cooling, medicaments, perfumes and preser-vatives, for example benzyl alcohol, benzoic acid, sodium benzoate, parahydroxybenzoic acid esters or sorbic acid, ethereal oils and the like, can be added. These ready-to-use ointments must then be packed in containers which are as air tight as possible so that evaporation of the water is pre-vented.
The hydrogels are a second type of hydrophilic oint-ment and one to which the present invention is directed. They -are generally prepared as follows: An anionic, crosslinked carboxyvinyl poly~er, insoluble but extremely swellable in water, having a high molecular weight of from about 860,000 to about 1,000,000, is suspended in water. The rree acid groups of the polymer are neutralized by the subsequent addition of a base, such as, for example, sodium hydroxide soluti.on, potas-sium hydroxide solution, a~monium hydroxide or triethanolamine.
During this neutralization, extensive thickening occurs and an aqueous mucil~ge is produced. To these gels can now be added the medicaments and lipophilic vehicle substances. As in the case of the emulsion ointments described above, these ready-to-use hydrogels have as their main constituent water ~nd they must therefore also be stored in tubes or other con~
tainers which close tightly. If not 80 packaged, the shelf life, stability and useability of the formulation is greatly restricted, both by evaporation of water and by possible mold contamination. Since the main constituent of these ointment
Among these ointments, hydrogels and emulsion ointments of the "oil-in-later" type rsee M~nzel, Versuch einer 3y~ema~ik der Saiben nacn gaieniscnen ~esicntspunkten Pharm. Acta Helv. 28, 320 (1953)J occupy a special position inasmuch as they can be easily washed off with water. Recause of their high water content they can be rubbed onto the skin easily with good penetration and, due to the evaporation of water, produce a pleasant cooling effect.
The emulsion ointments are generally prepared by machine. For example a typical procedure involves melting the fat phase, adding the required amount of hot water and the:l emulsifying the two phases with vigorous stirring, fre-quently with the aid of emulsifier~ and emulsion stabilizers such as thickeners or swelling agents. These latter com-~k `~
- 1 - ~
. .
- . .
-- ~ - ., .
1063~1Z3 ponents are intended to prevent subsequent separation of the emulsion. After cooling, medicaments, perfumes and preser-vatives, for example benzyl alcohol, benzoic acid, sodium benzoate, parahydroxybenzoic acid esters or sorbic acid, ethereal oils and the like, can be added. These ready-to-use ointments must then be packed in containers which are as air tight as possible so that evaporation of the water is pre-vented.
The hydrogels are a second type of hydrophilic oint-ment and one to which the present invention is directed. They -are generally prepared as follows: An anionic, crosslinked carboxyvinyl poly~er, insoluble but extremely swellable in water, having a high molecular weight of from about 860,000 to about 1,000,000, is suspended in water. The rree acid groups of the polymer are neutralized by the subsequent addition of a base, such as, for example, sodium hydroxide soluti.on, potas-sium hydroxide solution, a~monium hydroxide or triethanolamine.
During this neutralization, extensive thickening occurs and an aqueous mucil~ge is produced. To these gels can now be added the medicaments and lipophilic vehicle substances. As in the case of the emulsion ointments described above, these ready-to-use hydrogels have as their main constituent water ~nd they must therefore also be stored in tubes or other con~
tainers which close tightly. If not 80 packaged, the shelf life, stability and useability of the formulation is greatly restricted, both by evaporation of water and by possible mold contamination. Since the main constituent of these ointment
- 2 -, ... . .
; . ,. . . .;
1063~Z3 forwulations is water, the only packaging which is possible in order to ensure that the finished product reaches the con-sumer in a well-protected state is a relatively expensive packaging in tightly closing tubes. This type of packaging necessitates very large space requirements resulting in an increase in the stock volume.
In addition, pharmaceutical agents which are sensi-tive to moisture cannot be used in an ointment of this type since stability is limited by the water which is present.
Finally, the consistency of these ointments cannot be adjustèd by the ultimate user since it is determined by the manufacturer.
According to the present invention it has been found that granules or powders which contain such anionic, cross-linked carboxyvinyl polymer and an alkaline substance in which either or both of the polymer and the alkaline substance are coated with fats and/or emulsifiers, can be used to.prepare ointments. These particulate solid compositions can also con-tain an active ingredient such as a pharmaceutical or cosmetic ingredient or alternatively, the compositions can be manufactured free from any active ingredient, the active ingredient being introduced into the composition when the granules or powder is made up into an ointment. An essential constituent of the granules or powder is the anLonic, crossli`nked carboxyvinyl polymer which i8 insoluble but extremely swellable in water and which has a high molecular weight of from about 860,000 to about 1~000,000. Generally, the required amount is from about 1% to about 107., preferably 3% to 6%, based on the amount of granules
; . ,. . . .;
1063~Z3 forwulations is water, the only packaging which is possible in order to ensure that the finished product reaches the con-sumer in a well-protected state is a relatively expensive packaging in tightly closing tubes. This type of packaging necessitates very large space requirements resulting in an increase in the stock volume.
In addition, pharmaceutical agents which are sensi-tive to moisture cannot be used in an ointment of this type since stability is limited by the water which is present.
Finally, the consistency of these ointments cannot be adjustèd by the ultimate user since it is determined by the manufacturer.
According to the present invention it has been found that granules or powders which contain such anionic, cross-linked carboxyvinyl polymer and an alkaline substance in which either or both of the polymer and the alkaline substance are coated with fats and/or emulsifiers, can be used to.prepare ointments. These particulate solid compositions can also con-tain an active ingredient such as a pharmaceutical or cosmetic ingredient or alternatively, the compositions can be manufactured free from any active ingredient, the active ingredient being introduced into the composition when the granules or powder is made up into an ointment. An essential constituent of the granules or powder is the anLonic, crossli`nked carboxyvinyl polymer which i8 insoluble but extremely swellable in water and which has a high molecular weight of from about 860,000 to about 1~000,000. Generally, the required amount is from about 1% to about 107., preferably 3% to 6%, based on the amount of granules
- 3 -- . ~ .
or powder. -The anionic carboxyvinyl polymer above does not pro-duce a gel with water; on the contrary, gel formation occurs only after an alkaline agent has been added. If such an anionic carboxyvinyl polymer is introduced into water simul-taneously with an alkali however, spontaneous clumping of the polymer occurs. A homogeneous gel is then formed only after some hours. This is also true when the pulverulent carboxyvinyl polymer is introduced into an aqueous solution of an alkalinizing age~t. However when the anionic carboxy-vinyl polymer is coated with a thin protective film of an emulsifier and/or lipophilic vehicle substances and the poly- -mer is subsequently introduced into water, spontaneous clump-ing in the presence of the alkaline agent is avoided. The reverse is also possible. Thus the alkaline can be coated with an emulsifier and/or lipophilic vehicle substances so as to -~
delay its immediate dissolution when introduced into water.
In the presence of carboxyvinyl polymers, this leads to gradual thickening until a gel is prQduced without formation of lumps.
In addition to the alkaline agents mentioned above, ~ -ammonium bicarbonate, potassium carbonate, hexamethylenetetra-mine~ methylglucamine, lysine and glycine, and especially sodium carbonate, are particularly suitable as alkaline agents.
Generally, the proportion of the alkaline agent is from about 1% to about 10% especially 2~ to 5%, of the amount of granules ;
or powder.
;~; A mixture of the anionic carboxyvinyl polymer and -~ .
~ ' .
1063~23 ehe alkaline agent is, as noted above, not suitable for the preparation of a non-clumping ointment preparation. Only coating of at least of the ingredient of the mo1sture-sensitive combination of carboxyvinyl polymer and the alkaline agent with a thin hydrophobic film of an emulsifier and/or lipophilic vehicle substance permits the immediate formation of a smooth ointment from the granules or powder upon simply stirring with water. Advantageously, the lipophilic vehicle substance~ also provide a desirable slight lubrication 10 effect when the ointment is applied to the skin.
Emulsifiers include the "oil-in-water" type, such as, for example, sodium stearate, sodium dioctylsulfosuccinate, polyethylene glycol-400 stearate, polyoxyethylene-40 stearate, sorbitan monolaurate, sorbitan monostearate, polyethylene glycol sorbitan oleate, and the llk~. Sodium lauryl ~ulfate has proved especially advantageous. Generally, the amounts employed are from about 0.2% to about 3%, preferably 0.5% to 2%, based on the amount of granules or powdes.
Liquid hydrocarbons, such as liquid paraffin, and 20 liquid fats~ ~uch as triglycerides of caprylic to laurlc acid, oleic acid decyl ester, cetyl alcohol and isopropyl myristate, ~; can be employed as the lipophilic vehicle substances. Solid fats, such as for example, glycerol monostéarate and capric to stearic acid triglycerides are preferred a~d partial gly- ~
ceride8 of palmitic to stearic acid with a monoglyceride con- -tent of 40% to 90% are particularly suitable. These latter ~noglycerides can be dispersed by stirring with cold water and are therefore very suitable for the gra~ules or powders of the prese~t in-: ' ' . ' ' ' .......... . .. ' :' , :': ' . : :' , . .~ ', ~ . '' . ~ , , .
1063~Z3 invention. Generally, the amounts employed are from about 1% to about 30%, preferably 5% to 15%, based on the amount of granules or powder.
It has also proved advantageous if additional agents which increase the viscosity or which improve the disintegra-tion are added to the granules or powders. Because of their dissolving or swelling properties, these thickeners improve the distribution of the granules or the powder in water.
Such substances include for example, potato starch, dextrin, 10 -lactose, sorbitol, glucose, colloidal silica, corn starch, -mannit~ol and finely ground cellulose powder. me amounts used are from about lOZ to about 90Z, preferably 20% to 80%, based on the amount of granules or powder.
Granules, or a powder, for producing ointments can be prepared in the following way: ~-The anionic carboxyvinyl polymer with a molecular `~eight of 860,000 to 1,000,000 is mixed intimately with a medicament or a mixture of medicaments and one or more e~ten-ders. m is powder mixture is then moistened thoroughly with the emulsifier and/or one or more other lipophilic vehicle substances dissolved in organic solvents, such as for example, -~ carbon tetrachloride, chloroform~, methanol, ethanol, i~opropanol or methylene chlor~de, or mixtures thereof. The solvents are subsequently removed by evaporation. Depending on the degree to which the dry mixture is comminuted, this produces granules or a powder, to which onl~ an alkaline agent is still to be ; added.
.
~ Alternatively, the procedure described above is .. . . . . . . . .
, . ,, . , . ~ .
,: . - . .. . .
10 63~23 followed but the anionic carboxyv~nyl polymer and~or the all~line ~gent is coated wlth an emulsifier andtor other lipophilic vehicle substances.
If the use of organic solvents is not practicable, a gel c~n be prepared in wa~er from the anionlc carboxyvinyl polymer and an appropriate alkaline agent, all the necessary additives, such as, if appropriate, a medicament, extenders,'' ; an emulsifier ~nd a lipophilic vehicle substance, being in-corporated into the gel. The mass is freed from water by sub-sequent drying and'the dry product is brought to the desired particle size.
If, for ex~mple, 5 g of granules or a powder of this' type are introduced into 45 g of wa~er while stirring 810wly~
an ointment which is immediately ready for use is formed witbin 1 to 2 minutes. Depending on the ratio of the granules or pow-der to water, the consistency of such an ointment can be widely varied as desired. Thus a relatively solid formulation is ob-tained with 10 to 15% proportion of granules or powder, a rela-; tlvely thin formulation with 6 to 8% proportion of granules or powder and a lotion of low viscosity with 3 to 5% proportionof granules or powder.
It is possible to introduce a pharmaceutically active -' compound into the ointment with the water so that the granules , . .
or powder serve as a general ointment ba~e in which both the type of medicament(s) and concentration thereof cnn be varied -~ by'the plt~sician or pharmacist.
An oint _nt formulation of this type can readily be ~ 7 ~:.. , .. ", ". .. . . .. . . . .. .
1063~Z3 spread on and rubbed into the skin with any residues being easily washed off.
This concept offers a number of advantages. Up to a tenfold saving in space is achieved since the formulation is made up to the volume for application only as needed. This is especially important for example in the clinic, in the case of an emergency, in military operations or in the veterinary field when a large number ofpatientshave to be treated at once.
Relatively expensive packaging in tubes can be dispensed with in favor of a cheaper packaging such as sachets. The granules or powder for example can be sealed in an aluminium laminate.
Improved stability is realized in the case of moisture sensi-tive active compounds. Thus ointments can be prepared with agents which are not stable, or are stable for only a short time, in an aqueous medium. Ointments of a thinner or firmer ~, consistency can be prepared as desired by using more or less water. The physician, pharmacist or the user can thus ad~ust the physical nature of the ointment. The formulation can be prepared in any quantity, suitable either for a single hygienic 1 20 application or for several treatments.
The examples which follow are intended to illustrate in more detail the granules or powder, according to the inven-tion, or the preparation of ointments:
ExamPle 1 Granules for the preparation of a boric acid ointment Five parts of an anionic carboxyvinyl polymer with a mnlecular weight of 860,000 to 1,000,000 are suspended in . . , ~ ................... .
. , , . . .
300 parts of water and the suspensiDn is then thickened to fonm a gel by adding 3 parts of potassium carbonate in 100 parts of water. A mixture of 20 parts of boric acid powder, 45 parts of corn starch, 10 parts of dextrin, 5.5 parts of colloidal silica and 1.5 parts of sodium lauryl sulfate is added gradually. After the solid constituents have been mixed well, 10 parts of caprylic/lauric acid triglyceride are added.
The moist mass is then dried in a drier and brought to a suit-able grain size by sieving.
When stirred with 45 parts of water, 5 parts of the preparation produce a boric acid ointment which is suitable for immediate use.
Example 2 Powder for the PreParation of boric acid ointment Five parts of an anionic carboxyvinyl polymer with a molecular weight of 86~,000 to 1,000,000, 1.5 parts of sodium lauryl sulfate, 30 parts of boric acid powder, 35 parts of corn starch, 11.5 parts of cellulose powder and 5 parts of colloidal silica are mixed and then granulated with a solution of 10 parts of sorbitan monostearate in methylene chloride.
After drying, the mixture i8 sieved through an extremely fine sieve. 1.8 parts of lysine are moistened with a solution of 0.2 parts of oleic acid decyl ester in chloroform, dried and sieved through an extremely fine sieve. The two mixtures are then combined and mixed well.
When stirred with 45 parts of water, 5 parts of this powder give a boric acid ointment which i~ ready for use.
, . , - . . , . - - ............ ~ . . ~ . , .. , . ., . ~ .... .
, . . . . , , , , . . ~ . ~: . , :
Example 3 1063~)~3 Granules for the Preparation of a burn ointment Five parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 50 parts of sul- -fanilthiocarbamide, 19.5 parts of glucose and 5 parts of col-loidal silica are thoroughly mixed. A solution of 1.5 parts of polyoxyethylene-40 stearate and 10 parts of palmitic/stearic acid partial glyceride having a monoglyceride content of 90%
dissolved in 80 parts of methylene chloride i~ added. Granules 10 are formed which, after appropriate dry~ng, are brought to the desired grain gize by sieving. Ten parts of glycine are then added and mixed.
When stirred with 80 parts of water, 20 parts of these granules give a burn ointment which can be u~ed at once.
Ex~ple 4 Granules for the preparation of an antimYcotic ointment Ten parts of microfine clotri~azol, 5 parts of an anionic carbo~gvinyl poly~er with a molecular weight of 860,000 to 1,000,000, 45 parts of corn starch, 20 parts of a water- -20 soluble de~ctrin, 5.5 parts of colloidal silica and 1.5 parts - of sodium lauryl sulfate are intimately mixed and then granu-lated with a solution of 10 parts of palmitic/stearic açid partial glyceride havil~g a monoglyceride contont of 60X in 40 parts of methylelle chloride and 40 part~ of methanol. The solvent mi-cture i8 removed in a drier and the dry mixture i8 , ~
si ved to obtain granules of uniform size. Ttlree parts of grou~d sodlu~ carbonate are then also mi~ced in. With 10 parts . .. .
, . .
1063~Z3of water, 2 parts of this mixture give an ointment which can be applied at once.
Example 5 Powder for the Preparation of a nasal ointment 3.5 parts of an anionic carboxyvinyl polymer with a nolecular weight of 860,000 to 1,000,000, 34 parts of glucose, 10 parts of dextrin, 10 parts of corn starch and 8 parts of colloidal silica are mixed and granulated with a solution of 1 part of menthol, 5 parts of ethereal oil, 1 part of poly-ethylene glycol sorbitan oleate, 4 parts of oleic acid decylester and 20 parts of capric acid/stearic acid triglyceride in 60 parts of methylene chloride. The solvent is then removed by gentle drying and the dry mass is sieved to give a fine pow-der. 3.5 parts of methylglucamine are then admixed with this powder.
When stirred with 9 parts of water, 1 part of this powder produces a nasal ointment.
Example 6 Granules for the Pre~aration of an ointment for haemorrhoids Twenty parts of pulverized procaine hydrochloride, 1 part of water-soluble rutin, 5 parts of anionic carboxyvinyl polymer having a molecular weight of 860,000 to 1,000,000, 54 parts of dextrin, 5.25 parts of colloidal silica and 1.5 parts of sodium lauryl sulfate are mixed intensively with one another.
0.25 part of chamazulene and 10 parts of palmitic/
,~ -, ; ' '', ~ '' ' ', ':
- , . ' ,:
stearic acid partial glyceride with a monoglyceride content of 40X are dissolved ~n 75 parts of methylene chloride and the powder mixture i8 granulated with this solution. After drying the mixture, this is brought to a suitable grain size and 3 parts of powdered sodium carbonate are mi~ed ~n.
When stirred with 9 parts of water, 1 part of the granules gives a ready-to-use ointment for haemorrhoids.
E~ample 7 Granule~ for the preparation of a rheumatic ointment About 3.5 parts of heparinoid (corresponding to 50,000 IU), 6 parts of an anionic carbo~vinyl polymer with a molecular weight of 860,000 to 1,000,000, 44.2 parts of dextrin, 20 parts of cellulose powder and 5.5 parts of col-loidal silica are mi~ced well. Ten parts of glycerol mono-stearate, 2 parts of sorbitan monostearate and 5 parts of nicotinic acid benzyl ester are dissolved in 70 parts of meth~lene chloride and the powder mixture is granulated with this solution. After drying, the mixture i8 sieved to obtain granules of a uniform size and 4 parts of potassium carbonate 20 are mixed in.
When stirred with 40 parts of water, 5 parts of these granules give a rheumatic ointment which can be used immediately and which spreads easily.
E~camPle 8 Powder for the preparation of an acne ointment Four parts of finely powdered sodium carbonate are mixed with 16 parts of corn starch and the mi~cture is thoroughly . . . ~ , . .
. , .... ~ .
1063~23 moistencd with a solution of 3 parts of sorbitan monolaurate in 15 parts of chloroform. After the solvent has evaporated, the dry mixture is sieved through an extremely fine sieve.
Four parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 10 part~ of hexa-chlorophene powder, 3 parts of colloidal sulfur, 37 parts of corn starch, 10 parts of water-soluble dextrin, 5 parts of colloidal silica and 1 part of sodium lauryl sulfate are in-timately mixed and granulated with a solution of 7 parts of capric/stearic acid triglyceride in 40 parts of methylene chloride. The moist mixture is dried and then finely powdered.
The two mixtures are combined and mixed well.
When stirred with 45 parts of water, 5 parts of this powder ~ive an acne ointment which is ready for immediate use.
Example 9 Granules for the preparation of an acne ointment -Five parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 3 parts of col-loidal ~ulfur, 3 parts of very finely powdered salicylic acid, 5 parts of colloidal silica, 30 parts of mannitol, 30 parts of -corn starch and 1 part of sodium lauryl sulfate are mixed in-tensively and granulated with a solution of 5 parts of cetyl alcohol and 15 parts of palmitic/stearic acid partial glycer-ide with a monoglyceride content of 60% in 45 parts of methylene chloride. After drying, the mixture i8 sieved and 3 parts of hexamethylenetetramine are also admixed.
When stirred with 20 parts of water, 3 parts of these granules give a ready-to-use acne ointment.
:, . ` ~ , ~'. '., '
or powder. -The anionic carboxyvinyl polymer above does not pro-duce a gel with water; on the contrary, gel formation occurs only after an alkaline agent has been added. If such an anionic carboxyvinyl polymer is introduced into water simul-taneously with an alkali however, spontaneous clumping of the polymer occurs. A homogeneous gel is then formed only after some hours. This is also true when the pulverulent carboxyvinyl polymer is introduced into an aqueous solution of an alkalinizing age~t. However when the anionic carboxy-vinyl polymer is coated with a thin protective film of an emulsifier and/or lipophilic vehicle substances and the poly- -mer is subsequently introduced into water, spontaneous clump-ing in the presence of the alkaline agent is avoided. The reverse is also possible. Thus the alkaline can be coated with an emulsifier and/or lipophilic vehicle substances so as to -~
delay its immediate dissolution when introduced into water.
In the presence of carboxyvinyl polymers, this leads to gradual thickening until a gel is prQduced without formation of lumps.
In addition to the alkaline agents mentioned above, ~ -ammonium bicarbonate, potassium carbonate, hexamethylenetetra-mine~ methylglucamine, lysine and glycine, and especially sodium carbonate, are particularly suitable as alkaline agents.
Generally, the proportion of the alkaline agent is from about 1% to about 10% especially 2~ to 5%, of the amount of granules ;
or powder.
;~; A mixture of the anionic carboxyvinyl polymer and -~ .
~ ' .
1063~23 ehe alkaline agent is, as noted above, not suitable for the preparation of a non-clumping ointment preparation. Only coating of at least of the ingredient of the mo1sture-sensitive combination of carboxyvinyl polymer and the alkaline agent with a thin hydrophobic film of an emulsifier and/or lipophilic vehicle substance permits the immediate formation of a smooth ointment from the granules or powder upon simply stirring with water. Advantageously, the lipophilic vehicle substance~ also provide a desirable slight lubrication 10 effect when the ointment is applied to the skin.
Emulsifiers include the "oil-in-water" type, such as, for example, sodium stearate, sodium dioctylsulfosuccinate, polyethylene glycol-400 stearate, polyoxyethylene-40 stearate, sorbitan monolaurate, sorbitan monostearate, polyethylene glycol sorbitan oleate, and the llk~. Sodium lauryl ~ulfate has proved especially advantageous. Generally, the amounts employed are from about 0.2% to about 3%, preferably 0.5% to 2%, based on the amount of granules or powdes.
Liquid hydrocarbons, such as liquid paraffin, and 20 liquid fats~ ~uch as triglycerides of caprylic to laurlc acid, oleic acid decyl ester, cetyl alcohol and isopropyl myristate, ~; can be employed as the lipophilic vehicle substances. Solid fats, such as for example, glycerol monostéarate and capric to stearic acid triglycerides are preferred a~d partial gly- ~
ceride8 of palmitic to stearic acid with a monoglyceride con- -tent of 40% to 90% are particularly suitable. These latter ~noglycerides can be dispersed by stirring with cold water and are therefore very suitable for the gra~ules or powders of the prese~t in-: ' ' . ' ' ' .......... . .. ' :' , :': ' . : :' , . .~ ', ~ . '' . ~ , , .
1063~Z3 invention. Generally, the amounts employed are from about 1% to about 30%, preferably 5% to 15%, based on the amount of granules or powder.
It has also proved advantageous if additional agents which increase the viscosity or which improve the disintegra-tion are added to the granules or powders. Because of their dissolving or swelling properties, these thickeners improve the distribution of the granules or the powder in water.
Such substances include for example, potato starch, dextrin, 10 -lactose, sorbitol, glucose, colloidal silica, corn starch, -mannit~ol and finely ground cellulose powder. me amounts used are from about lOZ to about 90Z, preferably 20% to 80%, based on the amount of granules or powder.
Granules, or a powder, for producing ointments can be prepared in the following way: ~-The anionic carboxyvinyl polymer with a molecular `~eight of 860,000 to 1,000,000 is mixed intimately with a medicament or a mixture of medicaments and one or more e~ten-ders. m is powder mixture is then moistened thoroughly with the emulsifier and/or one or more other lipophilic vehicle substances dissolved in organic solvents, such as for example, -~ carbon tetrachloride, chloroform~, methanol, ethanol, i~opropanol or methylene chlor~de, or mixtures thereof. The solvents are subsequently removed by evaporation. Depending on the degree to which the dry mixture is comminuted, this produces granules or a powder, to which onl~ an alkaline agent is still to be ; added.
.
~ Alternatively, the procedure described above is .. . . . . . . . .
, . ,, . , . ~ .
,: . - . .. . .
10 63~23 followed but the anionic carboxyv~nyl polymer and~or the all~line ~gent is coated wlth an emulsifier andtor other lipophilic vehicle substances.
If the use of organic solvents is not practicable, a gel c~n be prepared in wa~er from the anionlc carboxyvinyl polymer and an appropriate alkaline agent, all the necessary additives, such as, if appropriate, a medicament, extenders,'' ; an emulsifier ~nd a lipophilic vehicle substance, being in-corporated into the gel. The mass is freed from water by sub-sequent drying and'the dry product is brought to the desired particle size.
If, for ex~mple, 5 g of granules or a powder of this' type are introduced into 45 g of wa~er while stirring 810wly~
an ointment which is immediately ready for use is formed witbin 1 to 2 minutes. Depending on the ratio of the granules or pow-der to water, the consistency of such an ointment can be widely varied as desired. Thus a relatively solid formulation is ob-tained with 10 to 15% proportion of granules or powder, a rela-; tlvely thin formulation with 6 to 8% proportion of granules or powder and a lotion of low viscosity with 3 to 5% proportionof granules or powder.
It is possible to introduce a pharmaceutically active -' compound into the ointment with the water so that the granules , . .
or powder serve as a general ointment ba~e in which both the type of medicament(s) and concentration thereof cnn be varied -~ by'the plt~sician or pharmacist.
An oint _nt formulation of this type can readily be ~ 7 ~:.. , .. ", ". .. . . .. . . . .. .
1063~Z3 spread on and rubbed into the skin with any residues being easily washed off.
This concept offers a number of advantages. Up to a tenfold saving in space is achieved since the formulation is made up to the volume for application only as needed. This is especially important for example in the clinic, in the case of an emergency, in military operations or in the veterinary field when a large number ofpatientshave to be treated at once.
Relatively expensive packaging in tubes can be dispensed with in favor of a cheaper packaging such as sachets. The granules or powder for example can be sealed in an aluminium laminate.
Improved stability is realized in the case of moisture sensi-tive active compounds. Thus ointments can be prepared with agents which are not stable, or are stable for only a short time, in an aqueous medium. Ointments of a thinner or firmer ~, consistency can be prepared as desired by using more or less water. The physician, pharmacist or the user can thus ad~ust the physical nature of the ointment. The formulation can be prepared in any quantity, suitable either for a single hygienic 1 20 application or for several treatments.
The examples which follow are intended to illustrate in more detail the granules or powder, according to the inven-tion, or the preparation of ointments:
ExamPle 1 Granules for the preparation of a boric acid ointment Five parts of an anionic carboxyvinyl polymer with a mnlecular weight of 860,000 to 1,000,000 are suspended in . . , ~ ................... .
. , , . . .
300 parts of water and the suspensiDn is then thickened to fonm a gel by adding 3 parts of potassium carbonate in 100 parts of water. A mixture of 20 parts of boric acid powder, 45 parts of corn starch, 10 parts of dextrin, 5.5 parts of colloidal silica and 1.5 parts of sodium lauryl sulfate is added gradually. After the solid constituents have been mixed well, 10 parts of caprylic/lauric acid triglyceride are added.
The moist mass is then dried in a drier and brought to a suit-able grain size by sieving.
When stirred with 45 parts of water, 5 parts of the preparation produce a boric acid ointment which is suitable for immediate use.
Example 2 Powder for the PreParation of boric acid ointment Five parts of an anionic carboxyvinyl polymer with a molecular weight of 86~,000 to 1,000,000, 1.5 parts of sodium lauryl sulfate, 30 parts of boric acid powder, 35 parts of corn starch, 11.5 parts of cellulose powder and 5 parts of colloidal silica are mixed and then granulated with a solution of 10 parts of sorbitan monostearate in methylene chloride.
After drying, the mixture i8 sieved through an extremely fine sieve. 1.8 parts of lysine are moistened with a solution of 0.2 parts of oleic acid decyl ester in chloroform, dried and sieved through an extremely fine sieve. The two mixtures are then combined and mixed well.
When stirred with 45 parts of water, 5 parts of this powder give a boric acid ointment which i~ ready for use.
, . , - . . , . - - ............ ~ . . ~ . , .. , . ., . ~ .... .
, . . . . , , , , . . ~ . ~: . , :
Example 3 1063~)~3 Granules for the Preparation of a burn ointment Five parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 50 parts of sul- -fanilthiocarbamide, 19.5 parts of glucose and 5 parts of col-loidal silica are thoroughly mixed. A solution of 1.5 parts of polyoxyethylene-40 stearate and 10 parts of palmitic/stearic acid partial glyceride having a monoglyceride content of 90%
dissolved in 80 parts of methylene chloride i~ added. Granules 10 are formed which, after appropriate dry~ng, are brought to the desired grain gize by sieving. Ten parts of glycine are then added and mixed.
When stirred with 80 parts of water, 20 parts of these granules give a burn ointment which can be u~ed at once.
Ex~ple 4 Granules for the preparation of an antimYcotic ointment Ten parts of microfine clotri~azol, 5 parts of an anionic carbo~gvinyl poly~er with a molecular weight of 860,000 to 1,000,000, 45 parts of corn starch, 20 parts of a water- -20 soluble de~ctrin, 5.5 parts of colloidal silica and 1.5 parts - of sodium lauryl sulfate are intimately mixed and then granu-lated with a solution of 10 parts of palmitic/stearic açid partial glyceride havil~g a monoglyceride contont of 60X in 40 parts of methylelle chloride and 40 part~ of methanol. The solvent mi-cture i8 removed in a drier and the dry mixture i8 , ~
si ved to obtain granules of uniform size. Ttlree parts of grou~d sodlu~ carbonate are then also mi~ced in. With 10 parts . .. .
, . .
1063~Z3of water, 2 parts of this mixture give an ointment which can be applied at once.
Example 5 Powder for the Preparation of a nasal ointment 3.5 parts of an anionic carboxyvinyl polymer with a nolecular weight of 860,000 to 1,000,000, 34 parts of glucose, 10 parts of dextrin, 10 parts of corn starch and 8 parts of colloidal silica are mixed and granulated with a solution of 1 part of menthol, 5 parts of ethereal oil, 1 part of poly-ethylene glycol sorbitan oleate, 4 parts of oleic acid decylester and 20 parts of capric acid/stearic acid triglyceride in 60 parts of methylene chloride. The solvent is then removed by gentle drying and the dry mass is sieved to give a fine pow-der. 3.5 parts of methylglucamine are then admixed with this powder.
When stirred with 9 parts of water, 1 part of this powder produces a nasal ointment.
Example 6 Granules for the Pre~aration of an ointment for haemorrhoids Twenty parts of pulverized procaine hydrochloride, 1 part of water-soluble rutin, 5 parts of anionic carboxyvinyl polymer having a molecular weight of 860,000 to 1,000,000, 54 parts of dextrin, 5.25 parts of colloidal silica and 1.5 parts of sodium lauryl sulfate are mixed intensively with one another.
0.25 part of chamazulene and 10 parts of palmitic/
,~ -, ; ' '', ~ '' ' ', ':
- , . ' ,:
stearic acid partial glyceride with a monoglyceride content of 40X are dissolved ~n 75 parts of methylene chloride and the powder mixture i8 granulated with this solution. After drying the mixture, this is brought to a suitable grain size and 3 parts of powdered sodium carbonate are mi~ed ~n.
When stirred with 9 parts of water, 1 part of the granules gives a ready-to-use ointment for haemorrhoids.
E~ample 7 Granule~ for the preparation of a rheumatic ointment About 3.5 parts of heparinoid (corresponding to 50,000 IU), 6 parts of an anionic carbo~vinyl polymer with a molecular weight of 860,000 to 1,000,000, 44.2 parts of dextrin, 20 parts of cellulose powder and 5.5 parts of col-loidal silica are mi~ced well. Ten parts of glycerol mono-stearate, 2 parts of sorbitan monostearate and 5 parts of nicotinic acid benzyl ester are dissolved in 70 parts of meth~lene chloride and the powder mixture is granulated with this solution. After drying, the mixture i8 sieved to obtain granules of a uniform size and 4 parts of potassium carbonate 20 are mixed in.
When stirred with 40 parts of water, 5 parts of these granules give a rheumatic ointment which can be used immediately and which spreads easily.
E~camPle 8 Powder for the preparation of an acne ointment Four parts of finely powdered sodium carbonate are mixed with 16 parts of corn starch and the mi~cture is thoroughly . . . ~ , . .
. , .... ~ .
1063~23 moistencd with a solution of 3 parts of sorbitan monolaurate in 15 parts of chloroform. After the solvent has evaporated, the dry mixture is sieved through an extremely fine sieve.
Four parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 10 part~ of hexa-chlorophene powder, 3 parts of colloidal sulfur, 37 parts of corn starch, 10 parts of water-soluble dextrin, 5 parts of colloidal silica and 1 part of sodium lauryl sulfate are in-timately mixed and granulated with a solution of 7 parts of capric/stearic acid triglyceride in 40 parts of methylene chloride. The moist mixture is dried and then finely powdered.
The two mixtures are combined and mixed well.
When stirred with 45 parts of water, 5 parts of this powder ~ive an acne ointment which is ready for immediate use.
Example 9 Granules for the preparation of an acne ointment -Five parts of an anionic carboxyvinyl polymer with a molecular weight of 860,000 to 1,000,000, 3 parts of col-loidal ~ulfur, 3 parts of very finely powdered salicylic acid, 5 parts of colloidal silica, 30 parts of mannitol, 30 parts of -corn starch and 1 part of sodium lauryl sulfate are mixed in-tensively and granulated with a solution of 5 parts of cetyl alcohol and 15 parts of palmitic/stearic acid partial glycer-ide with a monoglyceride content of 60% in 45 parts of methylene chloride. After drying, the mixture i8 sieved and 3 parts of hexamethylenetetramine are also admixed.
When stirred with 20 parts of water, 3 parts of these granules give a ready-to-use acne ointment.
:, . ` ~ , ~'. '., '
Claims (11)
PROPERTY OF PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A particulate solid composition which when ad-mixed with water rapidly produces an ointment suitable for medicinal or cosmetic use, said composition comprising an anionic crosslinked carboxyvinyl polymer having a molecular weight of from about 860,000 to about 1,000,000, which is water insoluble but water swellable, admixed with an alkaline substance, at least one of said polymer and said alkaline substance being coated with at least one member selected from the group consisting of emulsifiers and lipophilic substances.
2. A composition according to claim 1 which con-tains, exclusive of any medicament incorporated therein, from about 1% to about 10% of said polymer, from about 1%
to about 10% of said alkaline agent, at least one of said polymer and said alkaline substance being coated with a member selected from the group consisting of emulsifier in an amount of from about 0.2% to about 3% and/or lipophilic substances in an amount of from about 5% to about 15% with the balance consisting essentially of one or more thickening respectively swelling agents, all percentages being based on said composition.
to about 10% of said alkaline agent, at least one of said polymer and said alkaline substance being coated with a member selected from the group consisting of emulsifier in an amount of from about 0.2% to about 3% and/or lipophilic substances in an amount of from about 5% to about 15% with the balance consisting essentially of one or more thickening respectively swelling agents, all percentages being based on said composition.
3. A composition according to claim 1 wherein the alkaline substance is selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonium hydroxide, triethanolamine, ammonium bicarbonate, potassium carbonate, sodium carbonate, hexamethylenetetramine, methylglucamine, lysine and glycine.
4. A composition according to claim 3 wherein the alkaline substance is sodium carbonate.
5. A composition according to claim 1 wherein the emulsifier is selected from the group consisting of sodium lauryl sulfate, sodium stearate, sodium dioctylsulfonate, polyethylene glycol-400 stearate, polyoxyethylene-40 stearate, sorbitan monolaurate, sorbitan monostearate, polyoxyethylene oleyl ether, polyoxalkol and polyethylene glycol sorbitan oleate.
6. A composition according to claim 5 wherein the emulsifier is sodium lauryl sulfate.
7. A composition according to claim 1 wherein the lipophilic substance is selected from the group consisting of a liquid hydrocarbon, caprilic acid triglyceride, lauric acid triglyceride, oleic acid decyl ester, cetyl alcohol, isopropyl myristate, glycerol monostearate, capric acid triglyceride, stearic acid triglyceride and partial glycerides of palmitic or stearic acid having a monoglyceride content of from 40 to 90%.
8 A composition according to claim 7 wherein the lipophilic substance is a partial glyceride of saturated straight chain alkanoic acids having 16 to 18 carbon atoms, with a monoglyceride content of from 40 to 90%.
9. A composition according to claim 1 including one or more thickening or swelling agents.
10. A composition according to claim 9 wherein the thickening or swelling agent is selected from the group consisting of starch, dextrin, lactose, sorbital, glucose, silica, mannitol and cellulose powder.
11. Process for the preparation of a composition according to claim 1 which comprises coating particles of at least one of two components selected from the group con-sisting of an anionic crosslinked high molecular weight carboxyvinyl polymer and an alkaline substance with at least one member selected from the group consisting of emulsifiers and lipophilic substances, and combining said coated com-ponent with the other component, either coated or uncoated, into particulate solid composition.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752522178 DE2522178A1 (en) | 1975-05-17 | 1975-05-17 | GRANULES AND POWDER FOR THE MANUFACTURE OF Ointments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1063023A true CA1063023A (en) | 1979-09-25 |
Family
ID=5946916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA251,156A Expired CA1063023A (en) | 1975-05-17 | 1976-04-27 | Particulate compositions for ointment preparation |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS51142526A (en) |
| BE (1) | BE841914A (en) |
| CA (1) | CA1063023A (en) |
| DE (1) | DE2522178A1 (en) |
| FR (1) | FR2311530A1 (en) |
| GB (1) | GB1492917A (en) |
| IL (1) | IL49586A (en) |
| NL (1) | NL7605208A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5605938A (en) * | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| US5705178A (en) * | 1991-05-31 | 1998-01-06 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5546968U (en) * | 1978-09-21 | 1980-03-27 | ||
| JPS57171912A (en) * | 1981-04-14 | 1982-10-22 | Sumitomo Chem Co Ltd | Cream |
| DE3307816A1 (en) * | 1983-03-02 | 1984-09-06 | Schering AG, 1000 Berlin und 4709 Bergkamen | PROSTAGLANDINE-CONTAINING PHARMACEUTICAL PREPARATION AND ITS PRODUCTION |
| IT1204777B (en) * | 1986-02-04 | 1989-03-10 | Crinos Industria Farmaco | COMPOSITION FOR THE ETHERPORARY PREPARATION OF FORMULATIONS FOR TOPICAL APPLICATIONS FOR PHARMACEUTICAL AND COSMETIC USE |
| JP2622574B2 (en) * | 1987-04-01 | 1997-06-18 | 花王株式会社 | Bath additive |
| DE19724444C2 (en) * | 1997-06-10 | 1999-07-15 | Cospharcon Gmbh | Transdermal preparation and method of making the same |
| CA2299117A1 (en) * | 1999-02-24 | 2000-08-24 | Stiefel Research Institute, Inc. | Antimycotic compositions |
| JP2005047906A (en) * | 2003-07-16 | 2005-02-24 | Taisho Pharmaceut Co Ltd | Anti-inflammatory/analgesic composition for external application |
| CN113456668A (en) * | 2021-05-27 | 2021-10-01 | 齐万琴 | External ointment for women and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2484637A (en) * | 1946-08-20 | 1949-10-11 | Southern Res Inst | Powdered ointment base of methyl cellulose and sorbitol |
| BE535125A (en) * | 1954-01-25 | |||
| CH558659A (en) * | 1969-11-26 | 1975-02-14 | Orsymonde | PROCESS FOR THE PREPARATION OF A LYOPHILIZED COMPOSITION FOR HYGIENIC USE. |
-
1975
- 1975-05-17 DE DE19752522178 patent/DE2522178A1/en not_active Withdrawn
-
1976
- 1976-04-27 CA CA251,156A patent/CA1063023A/en not_active Expired
- 1976-05-14 NL NL7605208A patent/NL7605208A/en not_active Application Discontinuation
- 1976-05-14 JP JP51054449A patent/JPS51142526A/en active Pending
- 1976-05-14 GB GB20008/76A patent/GB1492917A/en not_active Expired
- 1976-05-14 IL IL49586A patent/IL49586A/en unknown
- 1976-05-17 BE BE167097A patent/BE841914A/en unknown
- 1976-05-17 FR FR7614823A patent/FR2311530A1/en active Granted
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5605938A (en) * | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| US5705178A (en) * | 1991-05-31 | 1998-01-06 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| US5705177A (en) | 1991-05-31 | 1998-01-06 | Gliatech Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| US5994325A (en) * | 1991-05-31 | 1999-11-30 | Gliatech Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| US6020326A (en) | 1991-05-31 | 2000-02-01 | Gliatech Inc. | Method for inhibition of bone growth by anionic polymers |
| US6083930A (en) * | 1991-05-31 | 2000-07-04 | Gliatech Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| US6127348A (en) * | 1991-05-31 | 2000-10-03 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS51142526A (en) | 1976-12-08 |
| GB1492917A (en) | 1977-11-23 |
| IL49586A0 (en) | 1976-07-30 |
| FR2311530B1 (en) | 1978-11-17 |
| NL7605208A (en) | 1976-11-19 |
| BE841914A (en) | 1976-11-17 |
| FR2311530A1 (en) | 1976-12-17 |
| DE2522178A1 (en) | 1976-11-25 |
| IL49586A (en) | 1978-12-17 |
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