GB2394895A - Proton pump inhibitor composition in paste form - Google Patents
Proton pump inhibitor composition in paste form Download PDFInfo
- Publication number
- GB2394895A GB2394895A GB0225926A GB0225926A GB2394895A GB 2394895 A GB2394895 A GB 2394895A GB 0225926 A GB0225926 A GB 0225926A GB 0225926 A GB0225926 A GB 0225926A GB 2394895 A GB2394895 A GB 2394895A
- Authority
- GB
- United Kingdom
- Prior art keywords
- formulation according
- pharmaceutical formulation
- proton pump
- pump inhibitor
- plasticizer
- 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.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 86
- 229940126409 proton pump inhibitor Drugs 0.000 title claims abstract description 32
- 239000000612 proton pump inhibitor Substances 0.000 title claims abstract description 32
- 238000009472 formulation Methods 0.000 claims abstract description 74
- 239000004014 plasticizer Substances 0.000 claims abstract description 20
- 239000004094 surface-active agent Substances 0.000 claims abstract description 18
- 239000008253 pharmaceutical paste Substances 0.000 claims abstract description 9
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 24
- 229960000381 omeprazole Drugs 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 10
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical group CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 9
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 9
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 9
- 239000001069 triethyl citrate Substances 0.000 claims description 9
- 235000013769 triethyl citrate Nutrition 0.000 claims description 9
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 9
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 8
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 8
- 229940113124 polysorbate 60 Drugs 0.000 claims description 7
- 125000005456 glyceride group Chemical group 0.000 claims description 6
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- 239000004150 EU approved colour Substances 0.000 claims description 3
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 claims description 2
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical group OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 2
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 2
- 150000002118 epoxides Chemical class 0.000 claims description 2
- 229960003174 lansoprazole Drugs 0.000 claims description 2
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 claims description 2
- 229960005019 pantoprazole Drugs 0.000 claims description 2
- 235000021317 phosphate Nutrition 0.000 claims description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 2
- 125000005498 phthalate group Chemical class 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229940068965 polysorbates Drugs 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims description 2
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 claims description 2
- DUHIKWRPAQIIBL-UHFFFAOYSA-N tris(2-ethylhexyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCC(CC)COC(=O)CC(O)(C(=O)OCC(CC)CCCC)CC(=O)OCC(CC)CCCC DUHIKWRPAQIIBL-UHFFFAOYSA-N 0.000 claims description 2
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims 1
- 239000006072 paste Substances 0.000 description 18
- 239000000796 flavoring agent Substances 0.000 description 8
- 235000019634 flavors Nutrition 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 5
- 235000017803 cinnamon Nutrition 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 229940116364 hard fat Drugs 0.000 description 4
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 241000282412 Homo Species 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000002610 basifying agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004667 medium chain fatty acids Chemical class 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- -1 propylene glycol diesters Chemical class 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000220225 Malus Species 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A pharmaceutical paste formulation for oral administration, which comprises a proton pump inhibitor, a surfactant, a plasticizer and an amphiphillic base.
Description
1 1 PHARMACEUTICAL PASTE FORMULATIONS
The present invention is concerned with improved pharmaceutical paste formulations containing proton pump inhibitors, and in particular improved pharmaceutical paste formulations containing omeprazole, and therapeutic uses thereof.
Omeprazole is described in U.S. patent 4,255,432. It is a potent inhibitor of gastric acid secretion that acts by inhibiting H+ K+ATPase, the enzyme involved in the final step of hydrogen ion production in the parietal cells, and has been used in the short term treatment of active duodenal and benign gastric ulcer and other gastric acid related diseases, in humans. Peptic ulcers are common also in some animals, particularly in horses. Although the etiology of gastro-
duodenal ulcers in horses has not been ascertained, it appears that stress plays important roles in some cases.
Omeprazole is highly acid labile and very slightly soluble in water and oral formulations have, therefore, been enteric-coated. Enteric coated formulations are expensive and time consuming to manufacture, and require elaborate technology and equipment. Another disadvantage of enteric-
coated formulations is the moisture sensitivity that can often be associated with such formulations. Various formulations have been reported for proton pump inhibitors, especially for omeprazole.
For example, W094/25070 discloses an oral composition containing a proton pump inhibitor in the form of enteric-coated dry particles mixed with a dry gelling agent, the mixture may then be made into a paste-like gel prior to administration. The composition, therefore, requires enteric coating, with the aforementioned disadvantages associated with such formulation. Furthermore, because such a moist gel is not stable during long-term storage at room temperature it cannot be
manufactured and sold as a ready-to-use formulation, rather it must be prepared ex tempore at the time of administration, making it inconvenient to use.
U.S. patents 5,708,017 and 6,316,481 describe paste formulations of proton-pump inhibitors comprising a proton-pump inhibitor, a thickening agent, a basifying agent and hydrophobic oily liquid vehicles. The thickening agent, along with a basifying agent, provides a non-acidic environment for the acid-labile omeprazole and thus has a stabilizing effect in the formulation.
The hydrophobic oily liquid vehicle comprises (i) a vegetable oil and (ii) triglycerides of medium chain fatty acids or propylene glycol diesters of medium chain fatty acids. The lubricant properties of the oil help the paste formulation to attain a desired degree of cohesiveness, plasticity, tenacity and ejectability. However, the common problem of syneresis, or separation of liquid from paste with time, has been reported with formulations as described in U.S. patents 5,708,017 and 6,316,481. Hence, there remains a need for pharmaceutical paste formulations having a blend of excipients that would alleviate the problems associated with prior art
formulations for thermolabile and moisture sensitive drugs.
The present invention now provides a stable, improved paste formulation for proton pump inhibitors. More particularly, there is provided by the present invention a pharmaceutical paste formulation for oral administration, which comprises a proton pump inhibitor, a surfactant, a plasticizer and an amphiphillic base.
The proton pump inhibitors used in the present invention are known compounds in the art, and methods for their preparation may be found in the literature. For example omeprazole is disclosed in EP 5129, lansoprazole in EP 174726, pantoprazole in EP 166287 and lemiprazole in GB 2,163,747. The preferred proton pump inhibitor used in the present invention is the compound known as omeprazole.
Many surfactants are reported in the literature, which can be used in formulations of the present invention, for example polyoxyethylenesorbitan monooleate, polyoxyethylene-sorbitan
l monopalmitate, polyoxyethylene-sorbitan monolaurate, polyoxyethylenesorbitan monostearate, polysorbates or the like. The more preferred surfactant for use in a formulation according to the present invention is polysorbate-60. The use of a surfactant in a formulation according to the present invention can aid emulsification of the fat and absorption of triglycerides, and thus can help to prepare a balanced paste formulation. A surfactant is typically present in a formulation according to the present invention at approximately 1% to 2 %w/w, based on the weight of the total formulation, depending on the amount of other ingredients present in a paste formulation according to the present invention. Preferably a surfactant is present in a formulation according to the present invention at approximately 0.5 to about 1.0 %w/w, based on the weight of the total formulation. Omeprazole is known to have poor intrinsic aqueous solubility and / or poor wetting capability, which has reduced the efficiency of its solubilisation within the gastrointestinal milieu when present in prior art pharmaceutical formulations. This reduction in solubility has led to poor
bioavailability of omeprazole in prior art formulations. We have now found that the use of
amphiphillic base in formulations according to the present invention can achieve improved bioavailability of a proton pump inhibitor present in a formulation according to the present invention. In particular, we have found that it is preferred to incorporate hard fats such as saturated polyglycolysed glycerides (also known in the art as Gelucire bases) to increase the bioavailability of the proton pump inhibitor present in a formulation according to the present invention. Examples of suitable gelucire bases include saturated polyglycolysed glycerides containing varying blends of (a) glycerides (mono-, di- and tri-), (b) mono- and allesters of such glycerides with polyethylene glycol and (c) low molecular weight polyethylene glycols.
Manipulation of the proportions of these blends has produced bases with a range of melting points (30 C to 50 C) and HLB values (for example 2 to 14), whereby the processing and release requirements can be selected.
A preferred amphiphillic base for use in a formulation according to the present invention is available under the trade mark Gelucire 33/01.
Suitable plasticizers for use in a formulation according to the present invention include for example adipates, epoxides, phosphates, phthalates, sebacates, azelates, citrates and the like.
Citrate plasticizer esters include triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, tri-(2-ethylhexyl)citrate and the like. A preferred plasticizer is triethyl citrate.
These citrate plasticizers can be produced from citric acid and are commonly used as plasticizers in pharmaceutical formulations, where small amounts thereof can increase free volume in such formulations and thus allow increased movement of macromolecules, such as amphiphillic bases.
The combined use of a plasticizer and an amphiphillic base in a formulation according to the present invention can increase the solubility of a proton pump inhibitor, such as omeprazole, present in the formulation and can also provide a stable paste formulation therefor. The present invention achieves, therefore, a stable paste formulation for acid labile and poorly soluble proton pump inhibitors, such as omeprazole.
A particularly preferred pharmaceutical paste formulation for oral administration according to the present invention comprises a proton pump inhibitor which is omeprazole, a surfactant which is polysorbate-60, a plasticizer which is triethyl citrate and an amphiphillic base which is Gelucire 33/01.
A formulation according to the present invention may also include additional ingredients commonly used in the formulation of human and veterinary medicines. For example, flavouring agents such as caramel, carrot, apple, cinnamon and sausage flavours; and colouring agents such as iron oxide, titanium dioxide, aluminum lakes and the like, can be added.
The amount of a proton pump inhibitor employed in a formulation according to the present invention can vary, and suitably can be in the range of about 1 to 50%w/w, based on the weight of the total formulation. Preferably the amount is about 50%w/w or less, based on the weight of the total formulation, and more preferably in the range of about 30 to about 40%w/w, based on
the weight of the total formulation. Suitably a surfactant is included in a formulation according to the present invention in the range of about 1 to 2%w/w, based on the weight of the total formulation; preferably in the range of about 0.5 to 1%w/w, based on the weight of the total formulation. Suitably a plasticizer is included in a formulation according to the present invention in the range of about 2 to 6%w/w, based on the weight of the total formulation; preferably in the range of about 3 to 5%w/w, based on the weight of the total formulation. An amphiphillic base is suitably included in a formulation according to the present invention in the range of about 50 to 70%w/w, based on the weight of the total formulation, depending on the amount of other excipients present in a paste formulation according to the present invention.
The incorporation of an acid labile drug substance, namely a proton pump inhibitor, in a formulation according to the present invention, results in an orally palatable and pharmaceutically stable paste. A paste formulation according to the present invention, and a pharmacologically active proton pump inhibitor contained therein, exhibit good stability.
Formulations according to the present invention are useful in the treatment of peptic ulcer diseases in humans or animals and can be used to deliver acid labile proton pump inhibitors orally for systemic activity in animals. The formulations of the present invention may be administered directly into the mouth of an animal, such as a horse, in need of anti-ulcer therapy; preferably a paste-dosing syringe can be used to facilitate drug administration. The consistency of a paste formulation according to the present invention is preferably such that it cannot easily drip out or be expelled once it is deposited on the dorsal part of an animal's tongue. The paste is essentially free of air bubbles, which enhances dosing accuracy.
There is also provided by the present invention a method of treating a human or animal patient suffering from or susceptible to a peptic ulcer or related disease, which method comprises administering to the human or animal patient a therapeutically effective amount of a formulation according to the present invention. The term "treatment" as used herein refers to prophylaxis in
susceptible patients, as well as the treatment of established symptoms of peptic ulcer or related disease. The present invention also provides a process of preparing a stable, improved paste formulation for a proton pump inhibitor, such as omeprazole, substantially as hereinbefore described, which process comprises admixing the proton pump inhibitor, a surfactant, a plasticizer and an amphiphillic base substantially as hereinbefore described, so as to yield a formulation according to the present invention, which formulation can suitably be coloured and / or flavoured.
More particularly, a formulation according to the present invention can be prepared by dispersing the proton pump inhibitor, in powder form, in a melted amphiphillic base (Gelucire) containing surfactant, plasticizer and optionally colouring agents, at a controlled temperature below about 30 C. A flavouring agent may then be added and mixed and homogenized to achieve desired consistency. A paste formulation thus obtained may be used to fill dosing syringes, which may be used directly to administer proton pump inhibitors to an animal in need of such treatment.
The present invention will now be further illustrated by the following Examples, which do not limit the scope of the invention in any way.
EXAMPLE 1
Sr No. Ingredients Standard quantity (%w/w) Omeprazole 37.0 2. Polysorbate-60 I.0 3. Triethyl citrate 4.0 4. Hard Fat (Gelucire 33/01) 57.7 5. Yellow oxide of iron 0.1 6. Cinnamon flavor 0.2
Polysorbate 60 and triethyl citrate were added to melted Gelucire base at 30-35 C, under stirring.
Colour dispersion was then added with mixing to the mass. The resulting mixture was cooled to below 30 C and omeprazole was added while mixing. Finally flavour was added, and mixing continued until a homogeneous mass was obtained.
EXAMPLE 2
Sr No. Ingredients Standard quantity (%w/w) Omeprazole 37.0 2. Polysorbate- 80 1.5 Tributyl citrate 4.5 4. Hard Fat (Gelucire 37/02) 57. 0 5. Yellow oxide of iron 0.1 Cinnamon flavor 0.2 Following the procedure of Example 1, omeprazole paste of the above composition was prepared. EXAMPLE 3
Sr No. ingredients Standard quantity (%w/w) 1. Omeprazole 37.0 2. Polysorbate - 60 1.0 3. Tributyl citrate 5.0 4. Hard Fat (Gelucire 39/01) 56.7 5. Yellow oxide of iron 0.1 Cinnamon flavor 0.2
Following the procedure of Example 1, omeprazole paste of the above composition was prepared. EXAMPLE 4
Sr No. Ingredients Standard quantity (%w/w) 1. Omeprazole 37.0 2. Polysorbate- 80 0.6 3. Triethyl citrate 3.8 4. Hard Fat (Gelucire 37/06) 58.3 5. Yellow oxide of iron 0.1 6. Cinnamon flavor 0.2 Following the procedure of Example 1, omeprazole paste of the above composition was prepared.
Claims (19)
1. A pharmaceutical paste formulation for oral administration, which comprises a proton pump inhibitor, a surfactant, a plasticizer and an amphiphillic base.
2. A pharmaceutical formulation according to claim 1, wherein the proton pump inhibitor is selected from the group consisting of omeprazole, lansoprazole, pantoprazole and lemiprazole.
3. A pharmaceutical formulation according to claim 2, wherein the proton pump inhibitor is omeprazole.
4. A pharmaceutical formulation according to any of claims 1 to 3, wherein the surfactant is selected from the group consisting of polyoxyethylene-sorbitan monooleate, polyoxyethylene-
sorbitan monopalmitate, polyoxyethylene-sorbitan monolaurate, polyoxyethylene-sorbitan monostearate and polysorbates.
5. A pharmaceutical formulation according to claim 4, wherein the surfactant is polysorbate-60.
6. A pharmaceutical formulation according to any of claims I to 5, wherein the amphiphillic base is a saturated polyglycolysed glyceride.
7. A pharmaceutical formulation according to claim 6, wherein the polyglycolysed glyceride is Gelucire 33/01.
8. A pharmaceutical formulation according to any of claims 1 to 7, wherein the plasticizer is selected from the group consisting of adipates, epoxides, phosphates, phthalates, sebacates, azelates and citrates.
9. A pharmaceutical formulation according to claim 8, wherein the citrate plasticizer is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate and tri-(2-ethylhexyl)-citrate.
10. A pharmaceutical formulation according to claim 9, wherein the plasticizer is triethyl citrate.
11. A pharmaceutical paste formulation for oral administration, which comprises a proton pump inhibitor which is omeprazole, a surfactant which is polysorbate-60, a plasticizer which is triethyl citrate and an amphiphillic base which is Gelucire 33/01.
12. A pharmaceutical formulation according to any of claims 1 to 11, wherein the proton pump inhibitor is present in an amount in the range of about 1 to 50%w/w, based on the weight of the total formulation.
13. A pharmaceutical formulation according to claim 12, wherein the proton pump inhibitor is present in an amount in the range of about 30 to about 40%w/w, based on the weight of the total formulation.
14. A pharmaceutical formulation according to any of claims 1 to 13, wherein the surfactant is present in an amount in the range of about 1 to 2%w/w, based on the weight of the total formulation.
15. A pharmaceutical formulation according to any of claims I to 14, wherein the plasticizer is present in an amount in the range of about 2 to 6%w/w, based on the weight of the total formulation.
16. A pharmaceutical formulation according to any of claims I to 15, wherein the amphiphillic base is present in an amount in the range of about 50 to 70%w/w, based on the weight of the total formulation.
17. A method of treating a human or animal patient suffering from or susceptible to a peptic ulcer or related disease, which method comprises administering to the human or animal patient a therapeutically effective amount of a formulation according to any of claims I to 16.
18. A process of preparing a pharmaceutical formulation according to any of claims I to 16, which process comprises admixing a proton pump inhibitor, a surfactant, a plasticizer and an amphiphillic base, so as to yield a formulation according to any of claims I to 16.
19. A process according to claim 18, which comprises dispersing the proton pump inhibitor, in powder form, in a melted amphiphillic base containing surfactant, plasticizer and optionally colouring agents, at a controlled temperature below about 30 C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0225926A GB2394895A (en) | 2002-11-06 | 2002-11-06 | Proton pump inhibitor composition in paste form |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0225926A GB2394895A (en) | 2002-11-06 | 2002-11-06 | Proton pump inhibitor composition in paste form |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0225926D0 GB0225926D0 (en) | 2002-12-11 |
| GB2394895A true GB2394895A (en) | 2004-05-12 |
Family
ID=9947342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0225926A Withdrawn GB2394895A (en) | 2002-11-06 | 2002-11-06 | Proton pump inhibitor composition in paste form |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2394895A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2046334A4 (en) * | 2006-07-25 | 2009-11-25 | Vecta Ltd | Compositions and meth0ds for inhibiting gastric acide secretion using derivatives of small dicarboxylic acids in combination with ppi |
| US7803817B2 (en) | 2005-05-11 | 2010-09-28 | Vecta, Ltd. | Composition and methods for inhibiting gastric acid secretion |
| US7981908B2 (en) | 2005-05-11 | 2011-07-19 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| WO2020200586A1 (en) | 2019-04-05 | 2020-10-08 | Arcelik Anonim Sirketi | A robot vacuum cleaner and the control method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5708017A (en) * | 1995-04-04 | 1998-01-13 | Merck & Co., Inc. | Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors |
| WO2000050038A1 (en) * | 1999-02-23 | 2000-08-31 | Merck & Co., Inc. | Pharmaceutical composition containing proton pump inhibitors |
| DE10061135C1 (en) * | 2000-12-07 | 2002-11-07 | Byk Gulden Lomberg Chem Fab | Stable gel preparation for oral administration of acid-labile drug, especially proton pump inhibitor, comprises multiple drug units dispersed in gel base |
-
2002
- 2002-11-06 GB GB0225926A patent/GB2394895A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5708017A (en) * | 1995-04-04 | 1998-01-13 | Merck & Co., Inc. | Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors |
| WO2000050038A1 (en) * | 1999-02-23 | 2000-08-31 | Merck & Co., Inc. | Pharmaceutical composition containing proton pump inhibitors |
| DE10061135C1 (en) * | 2000-12-07 | 2002-11-07 | Byk Gulden Lomberg Chem Fab | Stable gel preparation for oral administration of acid-labile drug, especially proton pump inhibitor, comprises multiple drug units dispersed in gel base |
Non-Patent Citations (1)
| Title |
|---|
| WPI ABSTRACT, Acc. Nr. 2002-714526/78; & DE 10061135 C1 (BYK GULDEN LOMBERG CHEM FAB) (07-11-2002) * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7803817B2 (en) | 2005-05-11 | 2010-09-28 | Vecta, Ltd. | Composition and methods for inhibiting gastric acid secretion |
| US7981908B2 (en) | 2005-05-11 | 2011-07-19 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| US9132082B2 (en) | 2005-05-11 | 2015-09-15 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| US9278080B2 (en) | 2005-05-11 | 2016-03-08 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| US9370481B2 (en) | 2005-05-11 | 2016-06-21 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion |
| EP2046334A4 (en) * | 2006-07-25 | 2009-11-25 | Vecta Ltd | Compositions and meth0ds for inhibiting gastric acide secretion using derivatives of small dicarboxylic acids in combination with ppi |
| US9233092B2 (en) | 2006-07-25 | 2016-01-12 | Vecta, Ltd. | Compositions and methods for inhibiting gastric acid secretion using derivatives of small dicarboxylic acids in combination with PPI |
| WO2020200586A1 (en) | 2019-04-05 | 2020-10-08 | Arcelik Anonim Sirketi | A robot vacuum cleaner and the control method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0225926D0 (en) | 2002-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0819004B1 (en) | Pharmaceutical composition containing proton pump inhibitors | |
| CA2362932C (en) | Pharmaceutical composition containing proton pump inhibitors | |
| GB2394895A (en) | Proton pump inhibitor composition in paste form | |
| WO2005000269A1 (en) | Pharmaceutical formulations comprising a proton pump inhibitor | |
| HK1041650B (en) | Pharmaceutical composition containing proton pump inhibitors | |
| HK1004658B (en) | Pharmaceutical composition containing proton pump inhibitors | |
| MXPA01008525A (en) | Pharmaceutical composition containing proton pump inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |