GB2086227A - Sodium cromoglycate reconstitutable powders - Google Patents
Sodium cromoglycate reconstitutable powders Download PDFInfo
- Publication number
- GB2086227A GB2086227A GB8132425A GB8132425A GB2086227A GB 2086227 A GB2086227 A GB 2086227A GB 8132425 A GB8132425 A GB 8132425A GB 8132425 A GB8132425 A GB 8132425A GB 2086227 A GB2086227 A GB 2086227A
- Authority
- GB
- United Kingdom
- Prior art keywords
- mixture according
- weight
- water
- water soluble
- sodium cromoglycate
- 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.)
- Granted
Links
- 229960000265 cromoglicic acid Drugs 0.000 title claims abstract description 30
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000000843 powder Substances 0.000 title description 8
- 239000000203 mixture Substances 0.000 claims abstract description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 42
- 235000000346 sugar Nutrition 0.000 claims abstract description 13
- 239000005720 sucrose Substances 0.000 claims abstract description 12
- 229930006000 Sucrose Natural products 0.000 claims abstract description 11
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 10
- 239000002245 particle Substances 0.000 claims description 16
- 150000002500 ions Chemical class 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 229910001385 heavy metal Inorganic materials 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 125000000185 sucrose group Chemical group 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 230000002009 allergenic effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 3
- 235000019640 taste Nutrition 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 2
- 208000004262 Food Hypersensitivity Diseases 0.000 description 2
- 206010016946 Food allergy Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- -1 Zn++ ions Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000020932 food allergy Nutrition 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 206010027654 Allergic conditions Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 229920003182 Surlyn® Polymers 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 201000005298 gastrointestinal allergy Diseases 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
A mixture useful in the treatment of conditions of the gastrointestinal tract of sodium cromoglycate of mass median diameter from 2 to 30 microns with a pharmaceutically acceptable water soluble carrier of sieve size from 200 to 1000 microns, the carrier having a solubility of greater than 1 to 5 by weight in water at 20 DEG C and preferably comprising a sugar e.g. sucrose. The mixture may be formulated in sachets for dissolution in water prior to oral administration.
Description
SPECIFICATION
Pharmaceutical formulation
This invention relates to a new pharmaceutical formulation.
Sodium cromoglycate is well known to be useful, when administered by inhalation, for the treatment of asthma. For this use a dry powder mixture is sold comprising fine particles of the drug and coarser (30--80 micron) particles of lactose in a 1:1 weight ratio. This formulation has a slightly bitter taste. The objective in this formulation is to provide a composition in which the particles of drug adhere to the coarse lactose, but are capabie of being shaken off the lactose in the airstream which is inhaled by the patient.This formulation is more fully described in British Patent Specification No. 1,242,211. A modification of this powder formulation in which the particle size of the lactose carrier is from 80 to 150 microns in size is disclosed in British Patent Specification No. 1, 381, 872 and a further modification in which the particle size of the drug is from 2 to 4 microns is disclosed in British Patent
Specification No. 1,410. 588.
Sodium cromoglycate has also been known for many years, e.g. from British Patent Specification
No. 1, 423, 985, to be useful for the treatment of conditions of the gastro-intestinal tract. Various formulations have been suggested for this use including hard, dense granules of the drug (as described in British Patent Specification No. 1, 549, 229), which have been put up in a capsule which is designed to be swallowed. These granules can also be removed from the capsule and dissolved in water.
However it has been found that the granules are slow to dissolve, and it has been found necessary to follow the tedious procedure of dissolving them in hot water to ensure complete dissolution, and then to dilute the resulting solution with cold water. Adding sodium cromoglycate powder directly to cold water results in dry, unwetted powder being trapped in a gel of dissolving sodium cromoglycate, and, in consequence, solution time is prolonged because of inadequate wetting/de-aeration. Food allergy is thought to start in the mouth, and the physicochemical properties of sodium cromoglycate, in relation to the anatomy and biochemical conditions of the gastro-intestinal tract, therefore indicate that it should be taken by the patient as a solution for maximum therapeutic benefit. These liquid formulations are prima facie attractive.However multidose liquid formulations inevitably require the inclusion of preservative substances which are undesirable in the treatment of the allergic conditions. Many of the conventionally used preservatives are chemically incompatible with sodium cromoglycate and the limited range of compatible substances have allergenic potential for the group of patients to be treated.
On the other hand unit dose liquid forms of drugs are expensive, and are technically very difficult to produce, especially when formulated aseptically without a preservative. Indeed we are unaware of any unpreserved liquid unit dose drug formulation being available commercially. Furthermore liquid dosage forms of all kinds are expensive to transport and store because of their high volume and weight per unit dose.
Tablets containing the drug have been contemplated, but tablet formulations contain excipients, which, as with the preservatives conventionally used in solutions, tend to be allergenic. Furthermore tablets tend to take a long time to dissolve and are therefore inconvenient to the patient.
As a finely divided powder, which is a primary requisite for rapid dissolution, sodium cromoglycate is cohesive, and in pure form aggregates into a gel-like mass in contact with water, especially in cold drinking water.
We have now found, however, that certain therapeutically acceptable carrier materials, classified into particular sized particles, have the property of forming a uniform surface coating of sodium cromoglycate, even in the absence of binding agents. The resulting mixture is free flowing with a uniform distribution of the drug and has the particular advantage that it dissolves rapidly and completely in cold water. Furthermore the formulation can be readily filled into unit dose containers, e.g. sachets, whereby it can be protected from the damaging effects of atmospheric moisture.
This product form has the advantage that it is cheap to produce and distribute, it maximises the drug's bio-availability with the minimum of inconvenience to the patient, and by using a non-allergenic excipient it minimises the chance of any allergic response to the formulation itself. A particular advantage of the formulation is that by selecting a sweet-tasting carrier substance, the unpleasant taste of sodium cromoglycate can be masked acceptably without the need for an artificial flavouring agent.
This is of particular value in the treatment of food allergic disease in children where the exclusion of artificial flavours in the diet is a pre-requisite of treatment and where, as with all patients, good compliance with the prescribed drug therapy is as difficult to achieve as it is essential.
As can be appreciated from the considerations set out above the pharmaceutical criteria which are applicable to oral and inhalation forms of the drug are entirely different, and indeed the medical conditions treated by the two different forms of the drug are dealt with by quite separate groups of medical specialist.
Thus, according to the invention we provide a mixture of sodium cromoglycate of mass median diameter from 2 to 30 microns with a pharmaceutically acceptable water soluble carrier of sieve size from 200 to 1000 microns, the carrier having a solubility of greater than 1 to 5 by weight in water at 20or.
The finely divided sodium cromoglycate preferably has a mass median diameter of from 2 to 10 microns, and more preferably from 3 to 6 microns with 90% of the particles being of less than 30 microns diameter. The particle size of the sodium cromoglycate when below 10 microns may be measured by means of a Coulter counter. When above 10 microns the particle size may be measured by sieving.
The water soluble carrier preferably has a particle size of from 200 to 500 microns, e.g. a mean size of from 270 to 370 microns. The particle size of the water soluble carrier may be measured by sieving.
The water soluble carrier is preferably a sugar, for example xylitol and even more preferably sucrose, e.g. beet sucrose. We naturally prefer to avoid sugars which are poorly absorbed and which can, in certain circumstances, cause diarrhoea. We also prefer the sugar to be in a form which will dissolve quickly in water.
The water soluble carrier preferably has a solubility of greater than 1 to 4 more preferably greater than 1 to 2 and most preferably greater than 1 to 1.5, by weight in water at 20"C.
Sucrose is a particularly acceptable excipient for the formulation since it combines in one substance the merits of ready availability in appropriate size grades, cheapness, the desired physical characteristics for coating with the drug, good crystal strength with a rapid aqueous dissolution rate, freedom from allergenic potential, and a degree of sweetness appropriate to mask the taste of sodium cromoglycate in proportions which are pharmaceutically and medically acceptable. In addition it has a low moisture content and with the crystal size selected does not aggregate either in manufacture or storage.
When the formulation is added to cold water the coated carrier, e.g. sucrose particles, remain separate during the dissolution process and this ensures that the individual particles of sodium cromoglycate are uniformly wetted, thus promoting rapid drug dissolution without gelling.
Other sugars may be used in place of sucrose, but many have disadvantages. Thus glucose has a negative heat of solution which militates against ease of dissolution, lactose is insufficiently water soluble nor is it very sweet and, because of its origins, may contain allergic impurities, and xylitol is expensive and is not readily available in the desired particle size.
We prefer the composition to contain an excess, e.g. a 2 to 20 times, and preferably a 4 to 1 5 times by weight excess, of the water soluble carrier, e.g. sugar, and especially just sufficient sugar to mask the taste of the sodium cromoglycate. The proportion of sugar will thus depend on the particular sugar used. However, we have found that with sucrose a suitable proportion is from 5 to 12, and especially from 7.5 to 10 parts by weight for each part by weight of sodium cromoglycate.
The formulation may be put up into unit dosages, e.g. sachets (which are preferably made of material which will prevent the ingress of water) containing from 50 to 300mg, e.g. 100 or 200mg, of sodium cromoglycate and from 1--39, e.g. about 29, of sugar. The unit doses may be administered from 1 to 6 times a day, preferably before, e.g. about 30 minutes before meals. The composition preferably contains a low proportion of 'heavy metal ions', as we have found that the presence of such ions tends to produce cloudy solutions when the composition is dissolved in water. By the term 'heavy metal ions' we mean ions of metals in groups Ila, Ib, llb, lila, IVa and IVb of the periodic table and of the transition metals.Specific 'metal ions' which are detrimental, in excessive concentrations (i.e. above about 20 ppm) in solutions made up from the compositions of the invention, are Pb++, Ca++, Mg++ and
in particular Fe++, Fe+++ and Zn++ ions. We particularly prefer to keep the concentration of Mg++ ions as low as possible, e.g. less than about 0.22 ppm.
The composition also preferably contains a low proportion of water, e.g. less than 2%, preferably less than 1% and typically about 0.5% by weight. We prefer to carry out the mixing, and forming of the mixture into unit doses, at a relative humidity of less than about 65%, e.g. from about 40 to 65%.
The composition preferably comprises particles of the relatively coarse carrier coated with a layer of the fine sodium cromoglycate. We have surprisingly found that we can achieve the same effect as with the so called 'ordered mixing' with many times larger proportion of fine sodium cromoglycate to carrier than would be expected from theoretical considerations. The composition also desirably is such that there is no caking of the blend between mixing and formation into unit dosages, e.g. sacheting. The
mixture also desirably is such that there is no, or very little, segregation when it is filled, stored and transported.
We prefer the composition to contain no other excipients than the water soluble carrier.
The compositions of the invention can be used in the treatment of a wide variety of conditions, e.g.
Crohn's disease (a condition of the small, and sometimes also of the large, intestine), atrophic gastritis (a condition of the stomach), ulcerative colitis (a condition of the rectum), proctitis (a condition of the
rectum and lower large intestine), coeliac disease (a condition of the small intestine), regional ileitis (a regional inflammatory condition of the terminal ileum), peptic ulceration (a condition of the stomach and duodenum), gastrointestinal allergy (e.g. milk, gluten, food additive etc. allergy), irritable bowel syndrome and gastrointestinal bleeding induced by administration of an anti-inflammatory, e.g.
indomethacin or aspirin.
The composition is particularly useful for the treatment of food allergy in children.
The compositions of the invention may be made by mixing the fine sodium cromoglycate with the coarse carrier e.g. in a planetary or a matrix mixer. Desirably a three (or greater) layer sandwich of the components is placed in the mixer before the mixing commences. The mixing should be carried out for a sufficient time to ensure as uniform a mix as possible. Mixing times of up to 60 minutes, but preferably of less than 1 5 minutes are generally suitable. The mixer is preferably such as not to change the particle sizes of the ingredients significantly during the mixing process.
The invention is illustrated but in no way limited by the following Examples.
EXAMPLE 1
Sodium cromoglycate 100mg 200mg
(Apex milled mass median diameter 3-6 microns,
greater than 90% less then 30 microns. Measured
as 'anhydrous' material)
Sucrose to 1.03g 2.01g
(Caster sugar sieve cut 90% greater than
1 50 microns, 90% less than 450 microns)
A sandwich of sucrose-sodium cromoglycate-sucrose was placed in a matrix mixer (100L Fielder) in which a main rotor passed through the base of the powder and a side chopper rotor disrupts the mass movement of the powder. A satisfactory degree of mixing is achieved after a time of from about 2 to 10 minutes of operation of the mixer. The formulations are put up in paper/foil/polyethylene or 'Surlyn' laminate sachets; the individual sachets being 40 x 75mm and produced in strips of five 160 x 75mm with perforations between each. These strips are cartoned for appropriate treatment periods, e.g. 50's, 60's, 100's etc.
EXAMPLE 2
2g of the mixture of Example 1 when poured into 80ml of tap water at 250C + 30C in a 1 00ml beaker stirred by a high speed stirrer (1200 rpm) dissolved (visual assessment) in 20-25 seconds. By way of contrast 200mg of granules of sodium cromoglycate mean size 1 20 microns took 45-50 seconds to dissolve.
Claims (25)
1. A mixture of sodium cromoglycate of mass median diameter from 2 to 30 microns with a pharmaceutically acceptable water soluble carrier of sieve size from 200 to 1000 microns, the carrier having a solubility of greater than 1 to 5 by weight in water at 200C.
2. A mixture according to Claim 1 , wherein the sodium cromoglycate has a mass median diameter of from 2 to 10 microns.
3. A mixture according to Claim 1 or 2, wherein the water soluble carrier has a particle size of from 200 to 500 microns.
4. A mixture according to any one of the preceding claims, wherein the water soluble carrier has a mean size of from 270 to 370 microns.
5. A mixture according to any one of the preceding claims, wherein the water soluble carrier is a sugar.
6. A mixture according to Claim 5, wherein the sugar is sucrose.
7. A mixture according to any one of the preceding claims, wherein the water soluble carrier has a solubility of greater than 1 to 4 by weight in water at 200C.
8. A mixture according to Claim 7, wherein the water soluble carrier has a solubility of greater than 1 to 2 by weight in water at 2O0C.
9. A mixture according to Claim 8, wherein the water soluble carrier, has a solubility of greater than 1 to 1.5 by weight in water at 2O0C.
10. A mixture according to any one of the preceding claims containing an excess by weight of the water soluble carrier.
11. A mixture according to Claim 10 containing from 2 to 20 times by weight excess of the water soluble carrier.
12. A mixture according to Claim 11 containing from 4 to 15 times by weight excess of the water soluble carrier.
13. A mixture according to Claim 12 containing from 5 to 12 parts by weight of sucrose for each part by weight of sodium cromoglycate.
14. A mixture according to Claim 13 containing from 7.5 to 10 parts by weight of sucrose for each part by weight of sodium cromoglycate.
1 5. A mixture according to any one of the preceding claims in unit dosage form containing from 50 to 300mg of sodium cromoglycate.
16. A mixture according to Claim 1 5 containing 100 or 200mg of sodium cromoglycate.
17. A mixture according to Claim 1 5 or 16 in the form of a sachet.
18. A mixture according to Claim 17, wherein the sachet is made of material which will prevent the ingress of water
1 9. A mixture according to any one of the preceding claims containing a low proportion of 'heavy metal ions', as hereinbefore defined.
20. A mixture according to any one of the preceding claims containing less than 2% by weight of water.
21. A mixture according to Claim 20 containing less than 1% by weight of water.
22. A mixture according to any one of the preceding claims containing no other excipient than the water soluble carrier.
23. A method of making a mixture according to Claim 1 which comprising mixing the components at a relative humidity of less than 65%.
24. A method according to Claim 23, wherein the relative humidity is from 40 to 65%.
25. A mixture according to Claim 1 and substantially as hereinbefore described in Example 1.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8132425A GB2086227B (en) | 1980-11-05 | 1981-10-28 | Sodium cromoglycate reconstitutable powders |
| IT24812/81A IT1217271B (en) | 1980-11-05 | 1981-11-02 | PHARMACEUTICAL FORMULATION IN CHROMOGLYCATED SODIUM POWDER |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8035457 | 1980-11-05 | ||
| GB8132425A GB2086227B (en) | 1980-11-05 | 1981-10-28 | Sodium cromoglycate reconstitutable powders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2086227A true GB2086227A (en) | 1982-05-12 |
| GB2086227B GB2086227B (en) | 1984-10-10 |
Family
ID=26277415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8132425A Expired GB2086227B (en) | 1980-11-05 | 1981-10-28 | Sodium cromoglycate reconstitutable powders |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2086227B (en) |
| IT (1) | IT1217271B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985252A (en) * | 1987-04-07 | 1991-01-15 | R. I. Ph. Recherche Informatique Et Pharmacie (S.A.R.L.) | Medication, dietetic product and hygienic product in the form of a powered composition obtained by adsorption of active ingredients on a rapidly dissolving sugar and process for obtaining said composition |
| GB2324962A (en) * | 1997-05-10 | 1998-11-11 | Hewlett Healthcare Limited | Chromone compositions for bio-availability to the small intestine |
| US7258872B1 (en) | 1998-11-11 | 2007-08-21 | Thornton & Ross Limited | Chromone enteric release formulation |
-
1981
- 1981-10-28 GB GB8132425A patent/GB2086227B/en not_active Expired
- 1981-11-02 IT IT24812/81A patent/IT1217271B/en active Protection Beyond IP Right Term
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985252A (en) * | 1987-04-07 | 1991-01-15 | R. I. Ph. Recherche Informatique Et Pharmacie (S.A.R.L.) | Medication, dietetic product and hygienic product in the form of a powered composition obtained by adsorption of active ingredients on a rapidly dissolving sugar and process for obtaining said composition |
| GB2324962A (en) * | 1997-05-10 | 1998-11-11 | Hewlett Healthcare Limited | Chromone compositions for bio-availability to the small intestine |
| GB2324962B (en) * | 1997-05-10 | 2001-10-03 | Hewlett Healthcare Ltd | Treatment of allergic conditions |
| US7258872B1 (en) | 1998-11-11 | 2007-08-21 | Thornton & Ross Limited | Chromone enteric release formulation |
Also Published As
| Publication number | Publication date |
|---|---|
| IT8124812A0 (en) | 1981-11-02 |
| GB2086227B (en) | 1984-10-10 |
| IT1217271B (en) | 1990-03-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20011027 |