EP3846787A1 - Novel composition of lapatinib of oral solid dosage form and method of manufacturing thereof - Google Patents
Novel composition of lapatinib of oral solid dosage form and method of manufacturing thereofInfo
- Publication number
- EP3846787A1 EP3846787A1 EP19857473.3A EP19857473A EP3846787A1 EP 3846787 A1 EP3846787 A1 EP 3846787A1 EP 19857473 A EP19857473 A EP 19857473A EP 3846787 A1 EP3846787 A1 EP 3846787A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- lapatinib
- pharmaceutical composition
- composition
- dosage form
- novel pharmaceutical
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention relates to novel oral solid dosage pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof, preferably in a tablet dosage form. Further, the present invention discloses the process for preparing the same. The present invention provides an economical and advanced dosage form over existing dosage form.
- Lapatinib is a small molecule of dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is orally active drug for breast cancer and used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).
- EGFR epidermal growth factor receptor
- lapatinib ditosylate monohydrate is represented as below:
- Lapatinib is disclosed in US patent no. WO1999035146 and is marketed under the brand name of TYKERB ® (by Glaxo Smith Kline) which is of 250 mg, orange colored, oval shaped -biconvex, film-coated tablet for oral administration.
- TYKERB ® by Glaxo Smith Kline
- Each 250 mg tablet of TYKERB ® contains lapatinib ditosylate monohydrate or 250 mg lapatinib free base along with the inactive ingredients magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate and for coating of orange film-coat, FD&C yellow no. 6/sunset yellow FCF aluminum lake, hypromellose, macrogol/PEG 400, polysorbate 80 and titanium dioxide.
- the recommended dosage of TYKERB ® for advanced or metastatic breast cancer is 1250 mg (5 tablets) given orally once daily on days 1-21 continuously in combination with capecitabine 2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on days 1-14 in a repeating 21 -day cycle.
- PCT publication no. W02010023187 discloses a pharmaceutical composition with a high percentage of lapatinib as active pharmaceutical ingredient present in an amount of more than 60% by weight based on the total weight of the composition.
- W02014128107 exemplifies a pharmaceutical composition
- a pharmaceutical composition comprises lapatinib as an active ingredient along with one binder, one disintegrant, one lubricant, and one filler, wherein the filler comprises microcrystalline cellulose in an amount of 10 to 30% by weight, relative to the total weight of the pharmaceutical composition.
- WO 2010/023188 discloses pharmaceutical compositions comprising lapatinib or a pharmaceutically acceptable salt thereof wherein a unit dose of the composition contains 1200 to 1300 mg of the active pharmaceutical ingredient calculated as the free base.
- WO2007143483 reveals a method of treating cancer by administration of a combination of pyrimidine derivatives and quinazoline derivatives, more particularly combination of pazopanib and lapatinib for treatment of cancer.
- Indian patent application 970/MUM/2014 claims a pharmaceutical composition comprising lapatinib and one or more pharmaceutically acceptable excipients wherein the composition comprises nanosized lapatinib, having the particle size an average of less than about 2000 nm.
- Lapatinib formulations available currently in the market generally use microcrystalline cellulose and magnesium stearate as excipients.
- Microcrystalline cellulose is a widely used excipient and used in many pill and tablet formulations.
- the mannitol is inert excipient and is readily water soluble excipient.
- Cellulose derivatives when used as major component in the formulation have tendency to swell and result into higher variation when products are subjected to dissolution or pK studies. Being water soluble excipient, mannitol do not hinder the absorption of product and hence would be reduction in drug loss.
- Mannitol provides quite good compressibility as well and imparts adequate density to formulation, thereby making the formulation process more robust and advantageous and importantly scalability becomes quite smooth.
- mannitol has definitely advantage overusing cellulose derivatives.
- Cellulose derivatives in many cases are reported to have more variable processing parameters and pose challenges in commercial manufacturing process. The extent of use of such excipients becomes a limiting factor and hence excipients like mannitol enjoys better advantages.
- Sodium starch glycolate also like most other excipients and bulk additives is not healthy in high doses. Sodium starch glycolate was found to lengthen disintegration time when utilized at high concentrations. Further, it is found that depending on the source, it can cause adverse effects on certain individuals. People with allergy to com or with celiac disease may experience adverse effects.
- the present invention discloses a novel pharmaceutical composition of lapatinib that exclude the excipients like microcrystalline cellulose and sodium starch glycolate. Therefore, it is technically advanced and improved over existing prior arts.
- the primary object of the present invention is to provide a novel pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof for oral solid dosage form.
- Another object of the present invention is to provide the pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof for oral solid dosage form, preferably a tablet dosage form.
- Another object of the present invention is to provide an economical and advanced dosage form over existing dosage form and with less side effects.
- Yet another object of the present invention is to provide a pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof having excellent dissolution profile and higher stability with minimum use of excipients.
- Yet another object of the present invention is to provide a novel process for preparation of oral solid dosage pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof.
- Still another object of the present invention is to provide a pharmaceutical composition comprising lapatinib for the use in treatment of advanced or metastatic breast cancer.
- Another object of the present invention is to provide process for the preparation of pharmaceutical composition comprising lapatinib ditosylate and hydroxyl propyl methylcellulose (suitable for hot melt extrusion) and other suitable excipients, which then was encapsulated in hard gelatin capsule dosage form wherein faster dissolution of the lapatinib is obtained in recommended dissolution media.
- Another object of the present invention is to improve the solubility of lapatinib by complexation with cyclodextrin and its various modified derivatives.
- the inclusion complex obtained was mixed with other suitable excipients and encapsulated or compressed to form lapatinib tablets 250mg / 500mg tablet.
- the present invention discloses a novel pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof preferably oral solid dosage form of a tablet with pharmaceutically acceptable excipients and method of preparation thereof.
- the pharmaceutical composition of present invention comprises lapatinib ditosylate monohydrate with one or more pharmaceutically acceptable excipients selected from the group comprising of at least one diluent, at least one disintegrant, at least one binder, at least one lubricant, wherein the composition does not comprise microcrystalline cellulose and sodium starch glycolate.
- lapatinib ditosylate is in micro sized form have a particle size distribution Ds>o with ranging from 5 to 50 pm, preferably 5 to 20 pm and more preferably 5-15 pm and the particle size is tightly controlled that enhances the drug dissolution of the drug product.
- the pharmaceutical composition according to the present invention is economical and advanced dosage form over existing dosage form, with less side effects and time efficient, especially for large-scale production, whereby the pharmaceutical composition shows a desired dissolution profile and higher stability with minimum use of excipients.
- Figure 1 illustrates particle size distribution curve of micro sized particles of lapatinib ditosylate monohydrate of the present invention.
- the present invention discloses a novel pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof preferably oral solid dosage form of a tablet.
- the pharmaceutical composition of the present invention comprises lapatinib preferably ditosylate monohydrate with one or more pharmaceutically acceptable excipients selected from the group consisting of at least one diluent, at least one disintegrant, at least one binder, at least one lubricant, wherein the composition does not comprise microcrystalline cellulose and sodium starch glycolate.
- a novel pharmaceutical composition comprising lapatinib as an active ingredient and one or more pharmaceutically acceptable excipients including diluents/filler, disintegrants, binders, lubricants, but not limited thereof.
- lapatinib ditosylate monohydrate as an active ingredient along with pharmaceutically acceptable excipients selected from lactose, mannitol, Soluplus ® (polyvinyl caprolactam-polyvinyl acetate -polyethylene glycol graft copolymer), povidone, croscarmellose sodium, magnesium stearate.
- pharmaceutically acceptable excipients selected from lactose, mannitol, Soluplus ® (polyvinyl caprolactam-polyvinyl acetate -polyethylene glycol graft copolymer), povidone, croscarmellose sodium, magnesium stearate.
- General composition for 250 mg tablet of lapatinib of the present invention is as under:
- the pharmaceutical composition of the present invention comprises lapatinib as active ingredient in the dosage form in range from 25% to 50% w/w.
- Another embodiment of present invention discloses 500 mg tablet of lapatinib.
- General composition for 500 mg tablet of lapatinib of the present invention is as below:
- the novel pharmaceutical composition of lapatinib oral dosage form of comprises a lapatinib, more preferably lapatinib ditosylate monohydrate as an active ingredient along with pharmaceutically acceptable excipients selected from lactose, mannitol, Soluplus ® , Pharmaburst ® 500, dicalcium phosphate, Polyplasdone ® XL, povidone, Hypromellose, croscarmellose sodium, magnesium stearate.
- the present invention discloses an immediate-release formulation of lapatinib ditosylate monohydrate for oral dosage form.
- lapatinib having very less solubility in water
- the active ingredient used in the present invention is micronized and the particle size is tightly controlled that enhances the drug dissolution of the drug product.
- ditosylate salt is used which exhibited good compression characteristics.
- Inventors of the present invention provides a pharmaceutical composition of lapatinib which would be considered as patient compliant due its better dissolution profile which ultimately leads to enhanced bioavailability.
- lapatinib that comprises lapatinib, preferably ditosylate, more preferably in its monohydrate form with one or more pharmaceutically acceptable excipients selected from at least one diluent, at least one disintegrant, at least one binder, at least one lubricant; wherein diluent is preferably selected from lactose, mannitol, Soluplus ® ; binder is preferably selected from povidone, HPMC; disintegrant is preferably selected from croscarmellose sodium, Polyplasdone ® XL (crospovidone), and lubricant is preferably selected from magnesium stearate, sucrose stearate or sodium stearyl fumarate.
- the amount of lubricant magnesium stearate in the tablet of the present invention is adjusted to avoid sticking to the tableting tools. Further, the film coated tablet of the present invention facilitate swallowing and patient compliance.
- This composition of the present invention lacks excipients including microcrystalline cellulose and sodium starch glycolate that are present in innovator’s product.
- Microcrystalline cellulose is insoluble in water and avoidance of that has enhanced the solubility and bioavailability of the composition of the present invention. Therefore, solubility of the active ingredient is increased.
- the present invention resulted in achieving good dissolution profile with minimum use of excipients. Therefore, stability of solid dosage forms of the present invention is quite higher.
- diluents may be selected from the group consisting of dextrates, dextrin, dextrose, fructose, l-O-a-D-glucopyranosyl-D-mannitol, glyceryl palmitostearate, hydrogenated vegetable oil, kaolin, lactitol, lactose, lactose monohydrate, maltitol, mannitol, maltodextrin, maltose, Soluplus ® (polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer), pregelatinized starch, sodium chloride, sorbitol, starches, sucrose, talc and xylitol or a mixture of one or more of said diluents.
- Disintegrants used for the preparation of solid oral dosage form are selected from the group consisting of carboxymethyl cellulose, low substituted hydroxypropyl cellulose, powdered cellulose, croscarmellose sodium, Polyplasdone ® XL (crospovidone), methylcellulose, polacrilin potassium, sodium alginate or a mixture of one or more of said disintegrants.
- Lubricants may be selected from the group consisting of calcium stearate, glyceryl palmitostearate, sodium benzoate, sodium stearyl fumarate, stearic acid, talc, zinc stearate and magnesium stearate or a mixture of one or more of said lubricants.
- the binders may be selected from the group consisting of hydroxyl propyl methyl cellulose (HPMC or hypromellose), polyvinyl pyrrolidone (povidone), hydroxyl propyl cellulose, polyvinyl alcohol, methyl cellulose, ethyl cellulose, gum arabic, alginic acid, polyethylene glycol (PEG), pregelatinized starch (PGS) and the like.
- HPMC hydroxyl propyl methyl cellulose
- povidone polyvinyl pyrrolidone
- hydroxyl propyl cellulose polyvinyl alcohol
- methyl cellulose methyl cellulose
- ethyl cellulose gum arabic
- alginic acid polyethylene glycol (PEG), pregelatinized starch (PGS) and the like.
- Glidants may be selected from the group consisting of colloidal silica, hydrophobic colloidal silica and magnesium trisilicate, such as talc; preferably, the glidants are selected from the group consisting of colloidal silica and hydrophobic colloidal silica.
- Solvents may be selected from the group consisting of short chain and long chain alcohols, acetone, and methylene dichloride (MDC).
- MDC methylene dichloride
- Coating mixture (Opadry ® ) or Tabcoat ® of present invention is consisting of hypomellose as film- forming agent, macrogol as plasticizer and polysorbate 80 as wetting agent. Further, titanium dioxide, yellow ferric oxide and red ferric oxide are used as colorants.
- the term“lapatinib” is not only limited to“lapatinib” per se but also includes in broader way its pharmaceutically acceptable derivatives thereof. These derivatives include pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable anhydrates, pharmaceutically acceptable isomers, pharmaceutically acceptable prodrugs, pharmaceutically acceptable enantiomers, pharmaceutically acceptable polymorphs, pharmaceutically acceptable esters, pharmaceutically acceptable tautomers, pharmaceutically acceptable complexes etc.
- lapatinib is present in the form of lapatinib ditosylate monohydrate in the present invention.
- active ingredient lapatinib have a particle size distribution Ds>o with ranging from 5 to 50 pm, preferably 5 to 15 pm.
- the present invention thus provides a pharmaceutical composition comprising lapatinib wherein the particle size of Lapatinib ditosylate is along with the unique formulation designed in such a way that lead to provide better dissolution profile and solubility of the drug.
- the particle size between range of 5 to 50 pm, preferably 5 to 15 pm gives better dissolution profile than highly reduced particle size.
- the pharmaceutical composition comprising lapatinib according to the present invention is administered orally through the solid dosage forms including tablets, capsules (filled with powders, pellets, beads, mini-tablets, pills, micro-pellets, small tablet units), MUPS (multiple unit pellet systems), disintegrating tablets, dispersible tablets, granules, and microspheres, multiparticulates, sachets (filled with powders, pellets, beads, mini-tablets, pills, micro-pellets, small tablet units, disintegrating tablets, dispersible tablets, granules, and microspheres, multiparticulates), powders for reconstitution and sprinkles, however, other dosage forms such as controlled release formulations, lyophilized formulations, modified release formulations, delayed release formulations, extended release formulations, pulsatile release formulations, dual release formulations and the like.
- the pharmaceutical composition comprising lapatinib according to the present invention may be administered in a solid oral dosage form of a tablet including film coated tablet, sugar coated tablet, chewable tablet, delayed release tablet, , multiple compressed tablet, enteric coated tablets, effervescent tablet, dispensing tablet.
- the present invention also discloses a method of manufacturing the oral solid dosage pharmaceutical composition of lapatinib or a pharmaceutically acceptable salt thereof.
- Lapatinib API and other excipients are sifted using appropriate size sieve and transferred to rapid mixer granulator (RMG) or any other suitable granulator. Then, dry mixing is done of the blend for 5 minutes.
- RMG rapid mixer granulator
- Binder is added to granulating fluid water under stirring. Stirring is continued till uniform solution is formed.
- dry mixture of the blend prepared in step (a) is blended in rapid mixer granulator (RMG) by adding binder solution prepared in stage (b) at an impeller speed of 80-100 RPM and chopper speed of 1000-2000 RPM.
- RMG rapid mixer granulator
- the wet granules prepared in step (c) are dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65°C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Solvent is evaporated during the drying stage.
- Dried granules prepared in step (d) are sifted using 20# sieve, milling of the oversize granules are done using clit mill.
- Lubricant is added in the blend prepared in step (e) and lubrication is carried out for 3 minutes.
- Dry blend was granulated in rapid mixer granulator (RMG) by adding binder solution of povidone K30 at an impeller speed of 80-100 RPM and chopper speed of 1000-2000 RPM.
- Wet granules prepared were kneaded for 30 seconds in rapid mixer granulator (RMG).
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- RMG rapid mixer granulator
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%. 4) Then after, dried granules prepared were sifted using 20# sieve, milling of the oversize granules were done using clit mill.
- FBP fluid bed processor
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- Lapatinib ditosylate monohydrate 405.00 mg Lactose monohydrate 349.70 mg Soluplus ® 37.30 mg
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- Lapatinib ditosylate monohydrate 405.00 mg Lactose (Flowlac ® l00) 387.00 mg
- Lapatinib API, lactose (Flowlac ® 100) and Povidone K30 were sifted using appropriate size sieve and transferred to blender followed by mixing for 30 minutes. 2) Then, disintegrant Croscarmellose sodium added to above blend and blended for 10 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- Lapatinib ditosylate monohydrate 405.00 mg Pharmaburst ® 500 387.00 mg Povidone K30 58.50 mg
- Lapatinib API, Pharmaburst ® 500 and povidone K30 were sifted using appropriate size sieve and transferred to blender and mixed for 30 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- Lapatinib API, dicalcium phosphate were sifted using appropriate size sieve and transferred to rapid mixer granulator (RMG). Then, dry mixing was done of the blend for 5 minutes.
- RMG rapid mixer granulator
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight. 8) Then, coating of core tablets was carried out using coating mixture of Opadry ® till the weight gain on core tablet was 3%.
- RMG rapid mixer granulator
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Lubricant magnesium stearate was added in the blend prepared in step (5) and lubrication was carried out for 3 minutes.
- Lubricated blend was compressed using suitable punch set at 900 mg tablet weight.
- the wet granules prepared were dried in the fluid bed processor (FBP) at inlet air temperature 45 to 65 °C till loss on drying (LOD) of the granules is less than 2%.
- FBP fluid bed processor
- Lubricated blend was compressed using suitable punch set at 1115 mg tablet weight.
- Dissolution rate is a critical property that need to study for final dosage form Comparative dissolution profile of the product of present invention with a reference product (tablet) was studied. Dissolution study of the pharmaceutical dosage of the present invention was carried out by HPLC.
- the dissolution method employed in the present invention is USP Apparatus II (paddle) with sinker at 55 RPM in 2% Tween 80 in 0.1 N HC1 for 45 min of time duration at (37 ⁇ 0.5) °C. Samples were taken at 10, 15, 30 and 45 minutes. The sample was filtered through a 0.45 pm syringe filter, transferred to HPLC vials and analyzed by HPLC. The following are the comparative dissolution data of the Lapatinib ditosylate monohydrate tablet of innovator reference product and final product of the present invention.
- composition in accordance with the present invention was subjected to stability study under stability analysis condition of 25°C ⁇ 2°C and relative humidity 60% ⁇ 5%. It was found to be adequately stable, as per general stability requirement under conditions. Moreover, the product is also stable in the similar manner in accelerated stability conditions.
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN201821032977 | 2018-09-03 | ||
PCT/IB2019/057324 WO2020049429A1 (en) | 2018-09-03 | 2019-08-30 | Novel composition of lapatinib of oral solid dosage form and method of manufacturing thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3846787A1 true EP3846787A1 (en) | 2021-07-14 |
EP3846787A4 EP3846787A4 (en) | 2022-05-25 |
Family
ID=69723001
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19857473.3A Pending EP3846787A4 (en) | 2018-09-03 | 2019-08-30 | Novel composition of lapatinib of oral solid dosage form and method of manufacturing thereof |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP3846787A4 (en) |
BR (1) | BR112021004047A2 (en) |
CL (1) | CL2021000512A1 (en) |
MX (1) | MX2021002441A (en) |
PH (1) | PH12021550451A1 (en) |
WO (1) | WO2020049429A1 (en) |
ZA (1) | ZA202101538B (en) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2158913A1 (en) * | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[(3-fluorophenyl)methoxy]phenyl]6-(5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
EP2158912A1 (en) * | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[3-fluorophenyl)methoxy)phenyl]6-[5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
EP2572199B1 (en) * | 2010-05-21 | 2017-03-08 | Novartis AG | Combination |
WO2012017448A2 (en) * | 2010-08-03 | 2012-02-09 | Hetero Research Foundation | Salts of lapatinib |
WO2015145145A1 (en) * | 2014-03-24 | 2015-10-01 | Cipla Limited | Pharmaceutical composition comprising lapatinib |
CN106511289A (en) * | 2015-09-10 | 2017-03-22 | 湖北生物医药产业技术研究院有限公司 | Benzenesulfonicacid lapatinib tablets and preparing method thereof |
-
2019
- 2019-08-30 MX MX2021002441A patent/MX2021002441A/en unknown
- 2019-08-30 WO PCT/IB2019/057324 patent/WO2020049429A1/en unknown
- 2019-08-30 BR BR112021004047-1A patent/BR112021004047A2/en unknown
- 2019-08-30 EP EP19857473.3A patent/EP3846787A4/en active Pending
-
2021
- 2021-03-01 CL CL2021000512A patent/CL2021000512A1/en unknown
- 2021-03-02 PH PH12021550451A patent/PH12021550451A1/en unknown
- 2021-03-05 ZA ZA2021/01538A patent/ZA202101538B/en unknown
Also Published As
Publication number | Publication date |
---|---|
CL2021000512A1 (en) | 2021-11-26 |
BR112021004047A2 (en) | 2021-05-25 |
PH12021550451A1 (en) | 2021-09-27 |
MX2021002441A (en) | 2021-03-25 |
ZA202101538B (en) | 2022-07-27 |
WO2020049429A1 (en) | 2020-03-12 |
EP3846787A4 (en) | 2022-05-25 |
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