Compositions comprising ciprofloxacin and celecoxib
Inventors
Ben Noon, Alon • Sterling, Jeffrey • Yacoby-Zeevi, Oron • Cohen Vered, Sharon
Assignees
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Publication Number
US-12097185-B2
Publication Date
2024-09-24
Expiration Date
Abstract
Embodiments relate to a tablet comprising celecoxib and ciprofloxacin or a pharmaceutically acceptable salt thereof, and low viscosity hydroxypropyl methylcellulose having a viscosity of less than 150 cP, when measured as a 2% solution in water at 20° C.
Core Innovation
The invention provides extended-release tablets comprising celecoxib and ciprofloxacin, or a pharmaceutically acceptable salt thereof, together with low viscosity hydroxypropyl methylcellulose (HPMC) having a viscosity of between 2 cP and 150 cP when measured as a 2% solution in water at 20°C. The formulation concept uses HPMC as a binder/control-release component within the tablet.
The disclosed tablets define HPMC characteristics and placement, including methoxyl and hydroxypropoxyl substitution levels and whether the HPMC is located in an extragranular component or an intragranular component. The invention also specifies target drug ratios between celecoxib and ciprofloxacin free base (1:1 to 1:100).
The invention further defines release and dissolution performance using USP apparatus conditions, including exposure in an acidic medium followed by pH 6.8 phosphate buffer with 1% SLS and defined percent release at specified times. Comparative examples show extended-release tablet batches with dissolution performance differences when varying fillers and HPMC types, and an alternate dissolution method is described.
The document also reports human fed-state pharmacokinetics for an extended-release fixed-dose combination tablet, including a synchronization concept for Tmax between celecoxib and ciprofloxacin at steady state. The document describes use of the disclosed tablet for treating amyotrophic lateral sclerosis (ALS) via administration of the disclosed tablets.
Claims Coverage
The independent claim covers a tablet composition defined by the combination of celecoxib and ciprofloxacin with a specific low-viscosity HPMC grade measured under a defined condition. The dependent claims add further inventive refinements including salt form, HPMC substitution, HPMC placement in extragranular/intragranular components, quantitative drug ratios, defined dissolution/release testing conditions, and pharmacokinetic relationships and related use.
Low-viscosity HPMC for extended-release tablet formulation
A tablet comprising celecoxib and ciprofloxacin or a pharmaceutically acceptable salt thereof, and low viscosity hydroxypropyl methylcellulose having a viscosity of between 2 cP and 150 cP, when measured as a 2% solution in water at 20°C.
Ciprofloxacin salt form as ciprofloxacin HCl
The tablet of the preceding claim wherein the pharmaceutically acceptable salt of ciprofloxacin is ciprofloxacin HCl.
Specified HPMC methoxyl and hydroxypropoxyl substitution ranges
The tablet of the preceding claim wherein the hydroxypropyl methylcellulose has methoxyl substitution between 28.0% and 30.0% and hydroxypropoxyl substitution between 7.0% and 12.0%.
Extragranular HPMC in a component-based tablet structure
The tablet of the preceding claim including an extragranular component and an intragranular component, with hydroxypropyl methylcellulose located in the extragranular component.
Celecoxib to ciprofloxacin free-base weight ratio constraint
The tablet of the preceding claim has a weight ratio of celecoxib to ciprofloxacin free base ranging from 1:1 to 1:100.
Defined dissolution and release profile under specified USP conditions
A tablet releasing ciprofloxacin and celecoxib in specified amounts over time when tested in 900 mL acetate buffer pH 4.5 using a Type II apparatus at 75 RPM and 37°C with 1% SLS present.
Overall, the claim coverage is centered on a celecoxib/ciprofloxacin extended-release tablet using low-viscosity HPMC defined by a specific measured viscosity range, with dependent features specifying ciprofloxacin HCl, HPMC substitution ranges, HPMC placement in extragranular vs intragranular components, drug weight-ratio constraints, and defined dissolution/release behavior under specified USP testing conditions.
Stated Advantages
Extended-release tablets with defined dissolution/release performance under specified test conditions.
Reported fed-state pharmacokinetics characterized by synchronization of Tmax between celecoxib and ciprofloxacin at steady state.
Documented Applications
Treatment of amyotrophic lateral sclerosis (ALS) via administration of the disclosed extended-release tablets.
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