Solid Solution Capsules for Oral Solubility of Compound 1
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Solution Overview
Problem
Existing pharmaceutical formulations of Compound 1, a C5a mediator, face challenges in manufacturability, stability, bioavailability, and pharmacokinetics, particularly due to its poor solubility in the gastrointestinal tract, leading to difficulties in oral administration.
Innovation Solution
A solid solution capsule formulation of Compound 1 is developed, comprising a non-ionic surfactant with an HLB value of at least 10 and a water-soluble solubilizer with a melting point above 37°C, ensuring complete dissolution and stability, using a process involving melting, mixing, and encapsulation to form a uniform matrix.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Compound 1 is formulated for oral administration, then bioavailability is improved, but solubility in the gastrointestinal tract deteriorates
Solution Approach 1:
The patent introduces a self-emulsifying vehicle comprising a non-ionic surfactant and a water-soluble solubilizer as an intermediary system. This vehicle acts as a mediator between Compound 1 and the gastrointestinal environment, forming micelles that solubilize the poorly water-soluble compound and enable its absorption across the intestinal membrane, thus resolving the contradiction between oral administration and solubility
2Ease of manufacture
If a conventional pharmaceutical formulation is used, then manufacturability is improved, but stability and bioavailability deteriorate
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation system by using a self-emulsifying vehicle that transforms from a solid or semi-solid state into micellar structures upon contact with gastrointestinal fluids. This parameter change enables the formulation to maintain stability during manufacturing while achieving enhanced bioavailability in the physiological environment
3Ease of operation
If Compound 1 is administered orally, then ease of administration is improved, but solubility in gastric pH deteriorates
Solution Approach 1:
The self-emulsifying vehicle serves as a protective intermediary that shields Compound 1 from the harsh gastric pH environment. The micellar structure formed by the surfactant and solubilizer protects the drug molecule during gastric transit, maintaining its solubility and preventing precipitation until it reaches the intestinal environment where absorption occurs
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 formulation provides excellent stability, bioavailability, and pharmacokinetic properties, maintaining Compound 1 in solution despite gastric pH, thereby addressing the solubility issues and enabling effective oral administration.
Implementation Method 1
a vehicle comprising at least one non-ionic surfactant having a hydrophilic-lipophilic balance (HLB) value of at least 10, and at least one water-soluble solubilizer having a melting point at or above 37° C.
Implementation Method 2
using a process involving melting, mixing, and encapsulation to form a uniform matrix
Data Source
AI summary
The present disclosure provides solid solution capsule formulations of Compound 1and methods of making the same. Also provided herein are methods of treating individuals suffering from or susceptible to a disease or disorder involving pathologic activation of C5a receptors by administering an effective amount of one or more solid solution capsules comprising Compound 1. Further provided herein are singe unit dosage capsules comprising certain amounts of Compound 1, and kits comprising a solid solution capsule comprising Compound 1.