Nebivolol Liquid Formulation for Solubility and Swallowing Ease
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Solution Overview
Problem
Nebivolol's poor solubility and low bioavailability in pharmaceutical compositions lead to difficulties in administering the drug, particularly for populations that have trouble swallowing solid oral dosage forms, such as children and the elderly, resulting in non-compliance and ineffective therapy.
Innovation Solution
Development of oral liquid formulations of Nebivolol comprising 0.05 to 10% Nebivolol or its pharmaceutically acceptable salt, 0.4 to 10% solubilizer, and 5 to 90% sweetener, with a pH range of 3 to 7, along with optional additives like flavoring agents, preservatives, binders, and buffers, to enhance solubility and patient compliance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If solid oral dosage forms (tablets) are used for Nebivolol administration, then the drug can be manufactured and stored easily, but patient compliance deteriorates due to difficulty in swallowing especially for children and elderly
Solution Approach 1:
The patent transforms the physical state of Nebivolol from solid (tablet) to liquid form, fundamentally changing the administration method. This parameter change enables easy swallowing for pediatric and geriatric patients while maintaining manufacturability through controlled formulation development
Solution Approach 2:
The patent introduces liquid vehicles and solubilizers as intermediary substances to deliver Nebivolol in a liquid form. These mediators enable the drug to be administered orally in liquid form, bridging the gap between manufacturable solid drug and patient-friendly liquid administration
2Ease of operation
If liquid formulations are developed to improve patient compliance, then ease of administration improves, but formulation complexity increases due to need for solubilizers and stabilizers
Solution Approach 1:
The patent selects liquid vehicles that perform multiple functions simultaneously: they solubilize Nebivolol, provide appropriate viscosity for administration, ensure stability, and enable accurate dosing. This multi-functionality reduces the need for multiple separate excipients, thereby simplifying the overall formulation despite the liquid state requirement
3Reliability
If Nebivolol is formulated to improve solubility, then bioavailability improves, but formulation stability deteriorates due to pH sensitivity
Solution Approach 1:
The patent carefully controls and adjusts the pH parameter of the liquid formulation to a specific range that simultaneously maximizes Nebivolol solubility (improving bioavailability) and maintains chemical stability. This precise parameter optimization resolves the contradiction between solubility enhancement and stability maintenance
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulations provide stable, easily administrable Nebivolol solutions that improve patient compliance and accessibility, particularly for pediatric and geriatric populations, while maintaining therapeutic efficacy.
Implementation Method 1
0.4 to 10% (w/w) of a solubilizer
Data Source
AI summary
The present disclosure provides a formulation comprising: 0.05 to 10% (w/w) of Nebivolol or a pharmaceutically acceptable salt thereof; 0.4 to 10% (w/w) of a solubilizer; and 5 to 90% (w/w) of a sweetener, wherein the formulation has pH in the range of 3 to 7. The present disclosure provides a reconstituted formulation comprising the formulation with a liquid vehicle. The present disclosure also provides process of preparing the formulations and methods thereof.