WO2022093134A1 - Pharmaceutical compositions comprising diclofenac potassium and relevant excipients - Google Patents
Pharmaceutical compositions comprising diclofenac potassium and relevant excipients Download PDFInfo
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- WO2022093134A1 WO2022093134A1 PCT/TR2020/050992 TR2020050992W WO2022093134A1 WO 2022093134 A1 WO2022093134 A1 WO 2022093134A1 TR 2020050992 W TR2020050992 W TR 2020050992W WO 2022093134 A1 WO2022093134 A1 WO 2022093134A1
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- Prior art keywords
- film coating
- sugar
- pharmaceutical composition
- composition according
- sucrose
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 40
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 title claims abstract description 36
- 229960004515 diclofenac potassium Drugs 0.000 title claims abstract description 36
- 239000000546 pharmaceutical excipient Substances 0.000 title claims abstract description 26
- 239000007888 film coating Substances 0.000 claims abstract description 90
- 238000009501 film coating Methods 0.000 claims abstract description 90
- 235000000346 sugar Nutrition 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims description 30
- 229930006000 Sucrose Natural products 0.000 claims description 26
- 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 description 26
- 239000010410 layer Substances 0.000 claims description 25
- 239000005720 sucrose Substances 0.000 claims description 25
- 239000003826 tablet Substances 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- 239000007941 film coated tablet Substances 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 16
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- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 23
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- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 150000004682 monohydrates Chemical group 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000012829 orthopaedic surgery Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004173 sunset yellow FCF Substances 0.000 description 1
- 235000012751 sunset yellow FCF Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
Definitions
- Diclofenac potassium is indicated for rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury.
- the present invention relates to a pharmaceutical compositions comprising “OPADRY SGR film coating system -Clear” as a film coating material, including sucrose and the other excipients.
- An object of the present invention is to provide a pharmaceutical composition in oral dosage form as a film coated tablet which provides immediate release of drug that exhibits acceptable bioavailability results.
- film coating layer means that a layer comprising sugar film coating system(s) having sucrose and other relevant excipients in a pharmaceutical composition.
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to the preparation of pharmaceutical compositions comprising diclofenac potassium and also relevant excipients; in the treatment of pain and inflammatory diseases, having an improved manufacturing process by using sugar based film coating systems.
Description
PHARMACEUTICAL COMPOSITIONS COMPRISING DICLOFENAC POTASSIUM AND RELEVANT EXCIPIENTS
Field of invention
The present invention relates to the preperation of pharmaceutical compositions comprising diclofenac potassium and also relevant excipients; in the treatment of pain and inflammatory diseases, having an improved manufacturing process by using sugar based film coating systems.
Background of the invention
Non-steroidal anti-inflammatory drugs (NSAIDs) are usually indicated for the treatment of acute or chronic pain and inflammatory conditions. One of the main types of NSAID is diclofenac that is well-known anti-inflammatory drug, firstly patented in 1965. Diclofenac was first synthesized by Alfred Sallmann and Rudolf Pfister and introduced as Voltaren by Ciba- Geigy (now Novartis) in 1973.
Diclofenac has analgesic and anti-inflammatory activity properties. Because of these properties, it is generally indicated for rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury.
In the market, there are many pharmacutical products which include diclofenac and pharmaceutically acceptable salts thereof, Diclofenac diethylamine, Diclofenac epolamine, Diclofenac sodium or Diclofenac potassium.
Diclofenac potassium has a chemical name as 2-(2, 6-dichloranilino) phenylacetic acid and its chemical structure is shown in the Figure 1. Diclofenac potassium has molecular weight of 334.239 g/mol, is a white to off-white or slightly yellowish crystalline powder.
Diclofenac potassium is indicated for rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury.
Figure 1
Diclofenac or its pharmaceutically acceptable salt thereof, diclofenac potassium is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and akylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. Also, It is used in combination with a prostaglandins analogue (misoprostol) as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers.
Voltaren is a trademark of GSK and Novartis (in Turkey market). This pharmaceutical product includes sodium salt of diclofenac and other wellknown excipients. Strength of Voltaren is 25mg to lOOmg with enteric or retard dosage forms in worldwide market. Except these dosage forms, sustained release and other non-oral administration f dosage orms are available in the pharmaceutical market.
Cataflam is a trademark of Novartis, this sugar coated product includes active ingredients of diclofenac potassium (in Turkey market). Cataflam composition comprising Silica aerogel, calcium phosphate, magnesium stearate, pregelatinized maize starch, polyvidone, sodium carboxymethyl starch, microcrystalline cellulose, red iron oxide (E172), titanium dioxide (E171), povidone, talc, sucrose, polyethylene glycol 8000.
Cataflam (sugar) film coated tablet is used for short-term treatment in the following acute conditions:
• Post-traumatic pain, inflammation and swelling, e.g. due to sprains,
• Post-operative pain, inflammation and swelling, e.g. following dental or orthopaedic surgery,
• Painful and/or inflammatory conditions in gynaecology, e.g. primary dysmenorrhoea or adnexitis,
• Migraine attacks,
• Painful syndromes of the vertebral column,
• Non-articular rheumatism,
• In severe painful inflammatory infections of the ear, nose or throat, e.g. pharyngotonsillitis, otitis.
EP1667664 relates to a pharmaceutical composition comprises diclofenac potassium with film coated tablet dosage form. The invention relates to a film coated tablet for use in field of pharmaceutical technology, comprises tablet core comprising diclofenac or its salt (potassium), and coating material comprising hydroxypropyl methylcellulose, stearic acid and microcrystalline cellulose. The purpose of said coating is to protect the tablet core, against moisture, oxygen and light and to ease swallowing of the tablet.
Summary of the invention
The present invention relates to the preperation of pharmaceutical compositions comprising diclofenac potassium and also relevant excipients; in the treatment of pain and inflammatory diseases, having an improved manufacturing process by using sugar based film coating systems.
The present invention relates a film coated tablet composition prepared by wet granulation method, comprising a tablet core and a film coating layer, wherein a. the core comprises diclofenac potassium in an amount of 25 mg to 100 mg, b. the weight ratio of the film coating layer to total tablet weight is between 18.0 to 22.0, and c. the film coating layer comprises one or more sugar film coating system having sucrose, wherein the weight ratio of sucrose to sugar film coating system is between 25% to 40%.
Detailed description of the invention
The present invention relates to the preperation of pharmaceutical compositions comprising diclofenac potassium and also relevant excipients; in the treatment of pain and inflammatory diseases, having an improved manufacturing process by wet granulaton method.
The present invention relates to the preparation of film coated tablet compositions comprising diclofenac potassium in a unit dosage form in the treatment of acute or chronic pain and inflammatory conditions, wherein process including wet granulaton method.
The present invention relates a film coated tablet composition prepared by wet granulation method, comprising a tablet core and a film coating layer, wherein a. the core comprises diclofenac potassium in an amount of 25 mg to 100 mg, b. the weight ratio of the film coating layer to total tablet weight is between 18.0 to 22.0, and c. the film coating layer comprises one or more sugar film coating system having sucrose, wherein the weight ratio of sucrose to sugar film coating system is between 25% to 40%.
The present invention relates a film coated tablet composition prepared by wet granulation method, comprising a tablet core and a film coating layer, wherein a. the core comprises diclofenac potassium in an amount of 25 mg to 100 mg, b. the weight ratio of the film coating layer to total tablet weight is between 18.0 to 22.0, preferably 20,0 (%), and c. the film coating layer comprises one or more sugar film coating system having sucrose, wherein the weight ratio of sucrose to sugar film coating system is between 25% to 40%.
The present invention relates to a pharmaceutical composition comprising diclofenac potassium and relevant excipients in a film coated tablet dosage form.
The present invention relates to an film coated tablet composition, wherein the formulation has a tablet core comprising diclofenac potassium, at least one pharmaceutically acceptable excipient and Sugar film coating system
The present invention relates a film coated tablet composition comprising diclofenac potassium in an amount of 25mg to lOOmg in a tablet core.
Preferably, the present invention relates a film coated tablet composition comprising diclofenac potassium in an amount of 25mg, 50mg, 75mg and lOOmg in seperately.
The present invention relates to a film coated pharmaceutical composition, the concentration ratio of the film coating layer and total tablet weight is between 18,0 (%) to 22,0 (%), preferably 20 (%).
The present invention relates a film coated pharmaceutical composition comprising diclofenac potassium, relevant excipients and the film coating layer.
The present invention relates a film coated pharmaceutical composition comprising a film coating layer, including one or more sugar film coating systems.
The present invention relates a film coated pharmaceutical composition comprising a film coating layer, including three sugar film coating systems.
The present invention relates to a film coated tablet composition, wherein sugar film coating systems are used as a film coating material in the film coating layer of composition.
The present invention relates to sugar film coating systems and/or similar coating systems with sugar.
In the present invention, the expression ’’sugar” means sucrose and other similar excipients in a pharmaceutical composition.
Sugar film coating system means a coating material comprising sugar amount between 25.0 % to 40.0 % in total tablet weight.
The present invention relates to a film coated tablet composition, wherein different kinds of sugar film coating system(s) are used as a film coating material, seperately or together.
The present invention relates to a pharmaceutical compositions comprising “sugar film coating system” as a film coating material, including sucrose and the other ingredients.
'The present invention relates to sugar film coating systems mean Opadry SGR film coating system. Structure of Opadry SGR film coating system has sucrose along with the other ingredients. Some of examples for Opadry SGR film coating system: Opadry SGR film coating system translucent, Opadry SGR film coating system brown, Opadry SGR film coating system dear and etc.
According to Colorcon website definition; Opadry® SGR is a high gloss, aqueous sugar film coating system that connects the art of conventional sugar coating with the science and automation of film coating.
OPADRY SGR film coating system comprising sucrose and the other excipients such as talc, HPMC 2910/Hypromellose, Macrogol/PEG, Medium chain triglycerides / Caprylin and Caprin, Glyceryl monostearate. Polyvinyl alcohol-part hydrolyzed, Titanium dioxide, Iron oxide red, FD&C Yellow #6/ Sunset Yellow FCF aluminum lake, Polysorbate 80.
The present invention relates to a pharmaceutical compositions comprising “OPADRY SGR film coating system-Translucent” as a film coating material, including sucrose and the other excipients.
The present invention relates to a film coated tablet composition, wherein OPADRY SGR film coating system-Translucent comprising sucrose concentration ratio of 40.0 %.
The present invention relates to a pharmaceutical compositions comprising “OPADRY SGR film coating system-Brown” as a film coating material, including sucrose and the other excipients.
The present invention relates to a film coated tablet composition, wherein OPADRY SGR film coating system- Brown comprising sucrose concentration ratio of 25.0 %.
The present invention relates to a pharmaceutical compositions comprising “OPADRY SGR film coating system -Clear” as a film coating material, including sucrose and the other excipients.
The present invention relates to a film coated tablet composition, wherein OPADRY SGR film coating system- Clear comprising sucrose concentration ratio of 25.0 %.
Sugar film coating systems have some advantages for pharmaceutical products;
• Fully formulated ready-to-use dry powder
• This material is suitable for use with many equipment
• It provides batch to batch uniformity with color adjustment
The present invention relates to a film coaled tablet composition, wherein wherein the film coating layer comprising one or more sugar film coating systems.
It is found when the weight ratio of film coating layer including sugar film coating systems and also total tablet weight is between a specific intervals mentioned above paragraphs, synergestic effect observed and it also provides an optimum formulation design for this film coated tablet product.
An object of the present invention is to provide a pharmaceutical composition in oral dosage form as a film coated tablet which provides immediate release of drug that exhibits acceptable bioavailability results.
The present invention relates a film coated pharmaceutical composition comprising tablet core, it is composed of components well known in the art and it is manufactures in a manner known per se.
According to literature in the state art, Diclofenac can be administered by different routes including oral, topical as well as by parenteral route. Oral doses of Diclofenac range from 12,5- 200,0 mg/day while parenteral doses range from 75,0 to 150,0 mg/day.
Tablet is a pharmaceutical oral dosage form (Oral Solid Dosage, or OSD) or solid unit dosage form. Tablets are defined as the solid unit dosage form of medicament or medicaments with suitable excipients.
Film coating is a basic step that can be used to improve product appearance, organoleptic properties, or to facilitate swallowing in tablet. Coatings materials are applied to improve surface properties of the substrate, such as appearance, adhesion, wetability, corrosion resistance, wear resistance, and scratch resistance.
Film coating provides protective layers and coloured of functional coatings and it involves. Film coating characteristic are systematic release of active ingredients, Gastric juice resistance, Taste masking and Visual attractiveness.
Advantages of using film coating process are less likely to affect disintegration, minimal weight gain, single stage process, maintains original shape of the core.
What the reasons for using film coating method is relevant to properties of appearance, stability, taste/odor masking and drug release characteristics.
Sugar film coating system is particularly chosen in formulation development for the film coated tablet dosage form including diclofenac potassium, relevant excipients.
It is found when the weight ratio of film coating layer and total tablet weight is between a specific intervals with using sucrose in specific interval in sugar film coating systems, batch to batch variation is not observed and it also provides to minimize invitro ve invivo variation for this film coated tablet product.
When using film coated process mentioned above with specific material of sugar film coating system, a shorter/optimum process design is provided for formulation development procedure and indirectly production procedure.
Wet granulation is the most widely used process of granulation in the pharmaceutical industry. Wet granulation process can be very simple or very complex depending on the characteristics of the powders and the available equipments.
Basicly, wet granulation method involves addition of a liquid solution (with or without binder) to powders, to form a wet mass or it forms granules by adding the powder together with an adhesive, instead of by compaction. Then, drying process starts and then sized to obtained granules with desired mesh. The granulate may then be tabletted /compressed, or other excipients may be added prior to tableting with suitable excipients.
The advantages of wet granulation method:
• Improving flow property and compression characteristics and increases density of granules
• Better distribution of color and soluble drugs if added in the binding solution.
• Reducing dust hazards
• Preventing segregation of powders
In one embodiment, the coating layer may be formed by any method, including compression, molding, dipping, or spray coating.
In the present invention, the expression "composition” is used to indicate a pharmaceutical composition or a medical device composition or a supplement composition or a food composition.
In the present invention, the expression “film coating system” means “sugar based film coating system” for a pharmaceutical composition.
In the present invention, the expression “film coating layer” means that a layer comprising sugar film coating system(s) having sucrose and other relevant excipients in a pharmaceutical composition.
The present invention relates to the preparation of pharmaceutical compositions comprising active ingredients and excipients, wherein process including in wet granulation method.
The present invention provides a pharmaceutical composition for use in the treatment acute or chronic pain and inflammatory conditions such as rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury.
In this invention, the composition comprising diclofenac potassium and relevant excipients can be used for in the treatment acute or chronic pain and inflammatory conditions.
In one embodiment, a pharmaceutical composition comprising effective amount of diclofenac potassium of the invention has a comparable bioavailability to the commercial form of diclofenac or salts.
In one preferred embodiment, the pharmaceutical composition comprising diclofenac potassium is bioequivalent to commercial form of diclofenac or salts.
In any of the embodiments described herein, wet granulation method of manufacturing process can be used according to API’s physical and chemical properties. Excipients can be selected according to environment of process.
Advantages
It is succeed fast and efficient manufacturing process by using this invention.
It is obtained effective and stable product by using sugar-containing film coating material compared to dragee dosage form.
The "Batch to batch variation" is very common problem for pharmaceutical manufacturing industry. Due to using this composition and process, the problem of "batch-to-batch variation" is solved and is not encountered.
An object of the present invention is to minimize the in-vitro and in-vivo variation by using mentioned pharmaceutical composition and manufacturing process above. The in-vitro and in- vivo variation problem is minimalized by using diclofenac potassium and relevant excipients with specific ranges in this pharmaceutical composition.
Another object of the present invention is to obtain pharmaceutical composition of diclofenac potassium with high stability and bioavalibility.
The tablet film coating technology helps to enhance, protect, or meet the desired release profile for the pharmaceutical product.
According to stability results and dissolution profile, the present invention shows satisfactory properties. (Figure 1-3, Table 1-3)
The present invention provides pharmaceutical composition comprising diclofenac potassium in a unit dosage form and relevant excipients, characterized by i) A simple manufacturing process ii) Stable and useful formulation,
The term "Diclofenac" includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof selected from the Diclofenac potassium, Diclofenac diethylamine, Diclofenac epolamine, Diclofenac sodium, preferably Diclofenac potassium.
The term "treatment" means any treatment of a disease or condition in a subject, such as a mammal, including: 1) preventing or protecting against the disease or condition, that is, causing
the clinical symptoms not to develop; 2) inhibiting the disease or condition, that is, arresting or suppressing the development of clinical symptoms; and/or 3) relieving the disease or condition that is, causing the regression of clinical symptoms.
In one embodiment, the pharmaceutical composition further comprises one or more of (i) a filler, (ii) a binder, (iii) a disintegrant (iv) a lubricant, (v) an lubricant, and (vi) a coating material(s).
Suitable fillers according to the present invention include, but are not limited to, dibasic calcium phosphate, tribasic calcium phosphate, kaolin, microcrystalline cellulose, silicated microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, magnesium trisilicate, lactose such as example the anhydrous form or the hydrate form such as the monohydrate form, sugars such as dextrose, maltose, saccharose, glucose, fructose or maltodextrine, sugar alcohols such as mannitol, maltitol, sorbitol, xylitol, powdered cellulose, precipitated calcium carbonate, sodium carbonate, sodium phosphate and com starch. The preferred fillers are microcrystalline cellulose, tribasic calcium phosphate and com starch.
Disintegrants can be selected from the group, but are not limited to, alginic acid, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminium silicate, microcrystalline cellulose, methyl cellulose, sodium starch glycolate, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidones, polacrilin potassium, starch, pregelatinised starch, sodium alginate, hydroxypropyl starch and other materials known to one of ordinary skill in the art. The combination of above-mentioned disintegrants can also be used. The preferred disintegrant is sodium starch glycolate.
Glidants can be selected from the group, but are not limited to, colloidal silicon dioxide, colloidal silica, cornstarch, talc, calcium silicate, magnesium silicate, magnesium trisilicate, amorphous silica, colloidal silicon, silicon hydrogel, powdered cellulose, silicon dioxide, talc, tribasic calcium phosphate and other materials known to one of ordinary skill in the art. The preferred glidant is colloidal silicon dioxide.
Lubricants according to the present invention include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, fumaric acid, sodium stearylfumarate, zinc stearate and polyethylene glycol. The preferred lubricant is magnesium stearate.
Example 1: Diclofenac potassium Film (Sugar) Coated Tablet
1. Stage 1 Sieving and Mixing
Sieving and mixing: diclofenac Potassium, tribasic calcium phosphate, microcrystalline cellulose, com starch, sodium starch glycolate and colloidal silicon dioxide.
2. Stage 2 Wet granulation
Adding Povidon K30, then wet granulation process.
3. Stage 3 Sieving and Mixing
Sieving and mixing: Sodium Starch Glycolate, colloidal silicon dioxide, magnesium stearate.
4. Stage 3 Film Coating
Using sugar film coating systems.
Thus the batch prepared with Example 1 show similar dissolution profile to RLD in different dissolution media which mimic different gastric pH area.
Dissolution profiles of RLD vs test product at 0.1N HCI
Time in Minutes
Figure 1: Dissolution profile of test product to RLD in O,1N HCI media.
Time in Minutes
Figure 2: Dissolution profile of test product to RLD in pH 4,5 media.
Dissolution profiles of RLD vs test product at ph 6.8
Figure 3: Dissolution profile of test product to RLD in pH 6,8 media.
Pharmaceutical products comprising diclofenac potassium prepared according to the invention were tested for stability. The other preparation with quantitative composition of Cataflam dragee (solid formulation) was prepared for a comparative stability study. The stability data of the invention formulation with the reference product is summarized in Table 1-3. Result of the stability study indicates that present diclofenac composition in accordance with the present invention exhibits excellent storage stability.
Table 1: Comparative data of the invention product of Example 1 with the reference product
Table 2: Comparative data of the invention product of Example 1 with the reference product
Table 3: Comparative data of the invention product of Example 1 with the reference product
Claims
1. A film coated tablet composition prepared by wet granulation method, comprising a tablet core and a film coating layer, wherein a. the core comprises diclofenac potassium in an amount of 25 mg to 100 mg, b. the weight ratio of the film coating layer to total tablet weight is between 18.0% to 22.0%, and c. the film coating layer comprises one or more sugar film coating system having sucrose, wherein the weight ratio of sucrose to sugar film coating system is between 25.0 % to 40.0 %.
2. The pharmaceutical composition according to claim 1, wherein the amount of diclofenac potassium is 25mg, 50mg, 75mg or lOOmg.
3. The pharmaceutical composition according to any one of the proceeding claims, wherein the weight ratio of the film coating layer to total tablet weight is 20.0 %.
4. The pharmaceutical composition according to any one of the proceeding claims, wherein the weight ratio of sucrose to sugar film coating system is 25.0 %.
5. The pharmaceutical composition according to any one of the proceeding claims, wherein the weight ratio of sucrose to sugar film coating system is 30.0 %.
6. The pharmaceutical composition according to any one of the proceeding claims, wherein the weight ratio of sucrose to sugar film coating system is 35.0 %.
7. The pharmaceutical composition according to any one of the proceeding claims, wherein the weight ratio of sucrose to sugar film coating system is 40.0 %.
8. A tablet composition according to any of preceding claims, wherein the film coating layer comprising one or more sugar film coating systems.
9. The pharmaceutical composition according to any one of the proceeding claims, wherein the film coating layer comprises three sugar film coating systems.
10. The pharmaceutical composition according to any one of the proceeding claims, wherein the composition further comprises at least one excipient selected from a filler, a binder, a disintegrant, a glidant, a lubricant and one or more sugar film coating materials.
11. A pharmaceutical composition according to any one of the proceeding claims for use in the treatment of acute or chronic pain and inflammatory conditions such as rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2020/050992 WO2022093134A1 (en) | 2020-10-26 | 2020-10-26 | Pharmaceutical compositions comprising diclofenac potassium and relevant excipients |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/TR2020/050992 WO2022093134A1 (en) | 2020-10-26 | 2020-10-26 | Pharmaceutical compositions comprising diclofenac potassium and relevant excipients |
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| WO2022093134A1 true WO2022093134A1 (en) | 2022-05-05 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006256961A (en) * | 2004-02-27 | 2006-09-28 | Dainippon Sumitomo Pharma Co Ltd | Sugar coated tablet |
| WO2009118764A1 (en) * | 2008-03-28 | 2009-10-01 | Panacea Biotec Limited | Pharmaceutical composition comprising diclofenac and paracetamol |
| JP2014077010A (en) * | 2000-10-06 | 2014-05-01 | Takeda Chem Ind Ltd | Thin layer sugar coated tablet and production method thereof |
| CN110585161A (en) * | 2019-10-11 | 2019-12-20 | 河南庚贤堂制药有限公司 | Production process of clofenyellow sensitive tablet coating |
-
2020
- 2020-10-26 WO PCT/TR2020/050992 patent/WO2022093134A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014077010A (en) * | 2000-10-06 | 2014-05-01 | Takeda Chem Ind Ltd | Thin layer sugar coated tablet and production method thereof |
| JP2006256961A (en) * | 2004-02-27 | 2006-09-28 | Dainippon Sumitomo Pharma Co Ltd | Sugar coated tablet |
| WO2009118764A1 (en) * | 2008-03-28 | 2009-10-01 | Panacea Biotec Limited | Pharmaceutical composition comprising diclofenac and paracetamol |
| CN110585161A (en) * | 2019-10-11 | 2019-12-20 | 河南庚贤堂制药有限公司 | Production process of clofenyellow sensitive tablet coating |
Non-Patent Citations (1)
| Title |
|---|
| TO DANIEL, BRAD PRUSAK, JASON TECKOE AND ALI RAJABI-SIAHBOOMI: "Investigation into a High Productivity Sugar Coating Formulation and Processing", AAPS POSTER PREPRINT, COLORCON, BPSI HOLDINGS, no. pr_aaps_high_prod_sugarfc_11_2017, 1 January 2017 (2017-01-01), pages 1 - 4, XP055938649 * |
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