Enhanced stability of novel liquid compositions
Inventors
AGISIM, Gary Robert • Friedline, Robert Alan • Patel, Shivangi Akash • Sertzen, César Iván • Shepperson, Vanessa Rose
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9308166-B2
Publication Date
2016-04-12
Expiration Date
Abstract
The present invention relates to compositions of pharmaceutical agents in combination with additional pharmaceutical agents in a mixture of polyethylene glycol, polyvinylpyrrolidone, and propylene glycol and a process of making the compositions.
Core Innovation
The invention relates to stable, palatable liquid oral pharmaceutical compositions containing guaifenesin and phenylephrine, with optionally other actives, formulated in a cosolvent system of polyethylene glycol, polyvinylpyrrolidone, and propylene glycol. The compositions aim to inhibit guaifenesin precipitation at cold temperatures while also addressing phenylephrine HCl degradation.
PEG and propylene glycol are described as reducing guaifenesin precipitation at cold temperatures, while PVP is described as further inhibiting precipitation. At the same time, PVP is stated to potentially contribute aldehydes that degrade phenylephrine, so PVP levels are optimized to balance guaifenesin precipitation inhibition with phenylephrine stability.
The specification provides formulation ranges and quantitative stability expectations tied to storage conditions. Experimental examples report visual precipitation-free times for guaifenesin at 4°C and -20°C for formulations with differing PVP levels, and phenylephrine stability over 3 months at 40°C and 75% RH, including total phenylephrine degradants and phenylephrine loss.
Claims Coverage
The partial claim set includes three independent composition claims and one independent process claim. Across these claims, the inventive coverage focuses on liquid oral pharmaceutical composition formulation ranges, visually precipitation-free guaifenesin stability at defined temperatures, phenylephrine degradation and loss thresholds under defined storage conditions, and a defined mixing and dissolution order using PVP, aqueous phase, and cosolvents before adding additional ingredients.
Liquid oral pharmaceutical composition with precipitation-free guaifenesin at 4°C
A liquid oral pharmaceutical composition comprising from about 0.1% to about 20% w/v polyvinylpyrrolidone, from about 5% to about 70% w/v polyethylene glycol, from about 1% to about 30% w/v propylene glycol, from about 1% to about 10% w/v guaifenesin, and from about 0.01% to about 1.0% w/v phenylephrine, wherein the composition is visually free of guaifenesin precipitation for at least 62 days at 4°C.
Liquid oral pharmaceutical composition with precipitation-free guaifenesin at -20°C
A liquid oral pharmaceutical composition comprising from about 0.1% to about 20% w/v polyvinylpyrrolidone, from about 5% to about 70% w/v polyethylene glycol, from about 1% to about 30% w/v propylene glycol, from about 1% to about 10% w/v guaifenesin, and from about 0.01% to about 1.0% w/v phenylephrine, further comprising about 4% w/v guaifenesin and about 0.10% w/v phenylephrine, wherein the composition is visually free of guaifenesin precipitation for 14 days at -20°C.
Liquid oral pharmaceutical composition with phenylephrine degradation and loss limits under accelerated storage
A liquid oral pharmaceutical composition comprising from about 0.1% to about 20% w/v polyvinylpyrrolidone, from about 5% to about 70% w/v polyethylene glycol, from about 1% to about 30% w/v propylene glycol, from about 1% to about 10% w/v guaifenesin, and from about 0.01% to about 1.0% w/v phenylephrine, wherein the composition comprises about 4% w/v guaifenesin and about 0.10% w/v phenylephrine, about less than 2% total phenylephrine degradants, as a percent weight over weight phenylephrine, and about less than 2% loss of phenylephrine from the initial total phenylephrine content, measured over a 3 month time period while stored at 40°C and 75% relative humidity.
Process for preparing an oral liquid composition using PVP dissolution then cosolvent addition
A process for preparing an oral liquid composition comprising mixing until dissolved from about 0.1% to about 20% w/v of polyvinylpyrrolidone in an aqueous phase, adding and mixing from about 1% to about 20% w/v of at least one pharmaceutical agent, subsequently adding and mixing water plus from about 1% to about 30% w/v of propylene glycol and from about 5% to about 70% w/v of polyethylene glycol, and subsequently adding and mixing one or more additional ingredients.
Overall, the independent composition claims require liquid oral formulations containing PVP, PEG, propylene glycol, guaifenesin, and phenylephrine with specific stability constraints expressed as visual freedom from guaifenesin precipitation at defined cold storage temperatures and/or quantitative limits on phenylephrine degradants and phenylephrine loss during 3 months at 40°C and 75% relative humidity. The independent process claim covers an ordered mixing and dissolution approach in which PVP is dissolved in an aqueous phase, at least one pharmaceutical agent is added, then water plus propylene glycol and polyethylene glycol are added and mixed, followed by addition of one or more additional ingredients.
Stated Advantages
Inhibiting guaifenesin precipitation at cold temperatures while maintaining visual stability.
Reducing phenylephrine HCl degradation by balancing PVP effects against phenylephrine stability.
Providing stable, palatable liquid oral pharmaceutical compositions.
Documented Applications
Stable, palatable liquid oral pharmaceutical composition for administration as an oral liquid.
Oral liquid formulation uses a cosolvent system of polyethylene glycol, polyvinylpyrrolidone, and propylene glycol to address guaifenesin precipitation and phenylephrine degradation. [procedural detail omitted for safety]
Interested in licensing this patent?