Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/38—Cellulose; Derivatives thereof
• • 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
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
• • 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
  • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• • 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
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4816—Wall or shell material
  • A61K9/4825—Proteins, e.g. gelatin
• • 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
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4833—Encapsulating processes; Filling of capsules
• • 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
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4841—Filling excipients; Inactive ingredients
  • A61K9/4866—Organic macromolecular compounds
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
  • C08B11/00—Preparation of cellulose ethers
  • C08B11/02—Alkyl or cycloalkyl ethers
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
  • C08L1/08—Cellulose derivatives
  • C08L1/26—Cellulose ethers
  • C08L1/28—Alkyl ethers

Definitions

• Fig. 4 is a graph showing the release over time of acetaminophen (APAP) from a composition of the invention containing a 2% solution of LTG methylcellulose dried overnight (shown as - ⁇ -) and from a composition containing a 2% solution of Methocel A4M methylcellulose dried overnight (shown as - ⁇ -).
• APAP acetaminophen
• the methylcellulose included in the present composition is capable of gelling at body temperature (about 35-37°C), forming stable hydrogels in an aqueous environment even at very low concentrations of methylcellulose resulting in a satisfactory sustained release performance.
• body temperature about 35-37°C
• stable hydrogels when used in this context is intended to mean hydrogels that retain their shape and are not completely dissolved or significantly eroded after immersion in 0.1 N HC1, pH 1.1, for 4 hours at 37°C.
• the methylcellulose is referred to as low temperature gelling (LTG) herein.
• the gelation temperature may for instance be determined as described in WO 2015/009796.
• a methylating agent such as methylene chloride is also added by conventional means to the cellulose pulp either before or after or concurrently with the caustic, generally in an amount of 2.0 to 3.5 mol methylating agent per mol anhydroglucose units in the cellulose.
• the methylating agent is added after the caustic.
• the LTG methylcellulose typically constitutes at least 50% by weight, preferably 60-100%, more preferably 70-100%, even more preferably 80-100%, and most preferably 90-100% by weight of the polymeric matrix.
• polymeric matrix When one or more other polymers are included in the polymeric matrix, they may be selected from cellulose ethers such as hydroxypropyl methylcellulose (HPMC), hydroxy ethyl methylcellulose, hydroxypropyl cellulose, methylcellulose with s23/s26 between 0.27 and 0.36 or between 0.38 and 0.42 or carboxymethylcellulose, or another polysaccharide such as sodium alginate or calcium alginate.
• HPMC hydroxypropyl methylcellulose
• methylcellulose with s23/s26 between 0.27 and 0.36 or between 0.38 and 0.42
• carboxymethylcellulose or another polysaccharide such as sodium alginate or calcium alginate.
• the LTG methylcellulose constitutes 100% by weight of the polymeric matrix.
• the dosage form is designed to provide a constant or nearly constant level of the active ingredient in plasma with reduced fluctuation via a slow, continuous release of the active ingredient over an extended period of time such as a period of between 4 and 30 hours, preferably between 8 and 24 hours to release all or almost all of the active ingredient from the dosage form.
• the present composition may suitably be prepared by providing a solution of LTG methylcellulose in a liquid diluent such as water in step (a) of the present process, optionally adding a surfactant to the solution as a processing aid.
• a surfactant to the solution as a processing aid.
• the active ingredient in powder or crystalline form and optionally one or more solid excipients may then be mixed with the LTG methylcellulose solution in step (b) of the present process.
• the unit dosage form may also be a capsule including the dried composition, preferably in the form of dry granules containing the mixture of LTG methylcellulose and active ingredient.
• the unit dosage form may also be in the form of a syringe or pouch pre-filled with the wet mixture: this dosage form may more readily be administered to young children.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Physiology (AREA)
• Nutrition Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Biochemistry (AREA)
• Materials Engineering (AREA)
• Inorganic Chemistry (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=64744643

Family Applications (1)

Country Status (4)

Cited By (1)

Citations (10)

Family Cites Families (5)

• 2019
  • 2019-12-17 US US17/312,411 patent/US20220031623A1/en not_active Abandoned
  • 2019-12-17 EP EP19836895.3A patent/EP3897729B8/en active Active
  • 2019-12-17 WO PCT/US2019/066704 patent/WO2020131780A1/en not_active Ceased
  • 2019-12-17 JP JP2021534753A patent/JP7535519B2/ja active Active
• 2025
  • 2025-03-17 US US19/081,897 patent/US20250248943A1/en active Pending

Patent Citations (10)

Non-Patent Citations (6)

Also Published As

Similar Documents

Legal Events