Stabilized prolonged release pharmaceutical composition comprising atypical antipsychotic
Inventors
Tiwari, Sunil Deviprasad • Redasani, Vijayendrakumar Virendrakumarji • Joshi, Prasad Shrikantrao • Sawarkar, Vaibhav Narayan • Shah, Ankur Janak
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9271939-B2
Publication Date
2016-03-01
Expiration Date
Abstract
The present invention provides stabilized prolonged release pharmaceutical compositions comprising atypical antipsychotic drug like paliperidone or pharmaceutically acceptable salts thereof without incorporating surfactant and/or water penetration enhancer. Such compositions are preferably in the form of a matrix wherein one or more release controlling agents are present in and/or on the matrix. Further, such compositions comprise one or more release controlling agent and exhibits desired in vitro release of drug with or without lag period. The invention also provides a process for the preparation of such compositions.
Core Innovation
The invention relates to stabilized prolonged release surfactant-free solid oral paliperidone tablet compositions. The compositions exclude surfactant and/or water penetration enhancers and are described as mainly matrix-based, while in dissolution testing the tablet compositions release 10% or less of paliperidone in at least two hours and achieve a desired in vitro dissolution profile.
The matrix core tablet comprises paliperidone, release controlling agents, a diluent, an antioxidant, a lubricant, and a glidant. The release controlling agents include polyethylene oxide and a granulated-free flowing cross-linked polyacrylate polymer in a specified ratio, and a coating layer is provided on the matrix core with release controlling agents as a mixture of hypromellose phthalate and ethyl cellulose, together with a plasticizer and talc.
Multiple process routes are described for forming the matrix core and applying the coating layer, including mixing, compression to obtain a matrix, and optional coating. Example formulations are described with specified excipients, and accelerated stability results are reported, indicating stable drug release and impurity profiles after storage conditions including 40°C/75% RH for 3 months.
Claims Coverage
The provided claims content contains five inventive features focused on a stabilized prolonged-release surfactant-free solid oral paliperidone tablet composition, dissolution performance, matrix and coating layer component selections, tightened dissolution windows, and a manufacturing process.
Stabilized prolonged release surfactant-free paliperidone dissolution performance
A stabilized prolonged release surfactant-free solid oral paliperidone tablet composition that upon dissolution testing releases 10% or less of paliperidone in at least two hours.
Matrix core with specified paliperidone and release controlling agents
A matrix core tablet comprising paliperidone; polyethylene oxide and a granulated-free flowing cross-linked polyacrylate polymer in a ratio of about 1:1 by weight; diluent microcrystalline cellulose; antioxidant butylated hydroxyl toluene; lubricant magnesium stearate; and glidant colloidal silicon dioxide, each with specified weight-percent ranges.
Coating layer with hypromellose phthalate and ethyl cellulose mixture
A coating layer coated on the matrix core tablet, comprising a mixture of hypromellose phthalate and ethyl cellulose in a ratio of about 1:0.5, together with plasticizer dibutyl sebacate and talc, each with specified weight-percent ranges.
Tightened dissolution time windows at 10% or less
Dependent composition refinements specify that the tablet composition upon dissolution testing releases 10% or less of paliperidone in at least three hours, in at least four hours, or in at least six hours.
Manufacturing process defined by mixing, compressing, and coating
A process for making a stabilized prolonged release surfactant-free solid oral pharmaceutical composition including mixing, compressing to obtain a matrix, and coating the matrix with a mixture comprising release controlling agent, plasticizer dibutyl sebacate, and talc.
The claim coverage centers on a stabilized prolonged-release surfactant-free solid oral paliperidone tablet that meets a dissolution-release ceiling of 10% or less over defined time thresholds, implemented via a matrix core with specified paliperidone and polyethylene oxide/cross-linked polyacrylate release controlling agents, and a coating layer containing a hypromellose phthalate/ethyl cellulose mixture plus dibutyl sebacate and talc. Dependent claims further narrow dissolution performance windows and define a mixing, compression, and coating process for manufacture.
Stated Advantages
Provides dissolution testing performance releasing 10% or less of paliperidone in at least two hours.
Achieves a desired in vitro dissolution profile while excluding surfactant and/or water penetration enhancers.
Stable drug release and impurity profiles are reported after 3 months under accelerated stability conditions including 40°C/75% RH.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?