Calcifediol Soft Capsule Composition for Immediate Oral Absorption
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Solution Overview
Problem
Calcifediol, with its high lipophilicity and poor water solubility, poses challenges in formulating immediate release pharmaceutical preparations for oral administration with suitable bioavailability, as existing formulations like Hidroferol® and controlled release solid formulations do not achieve optimal absorption.
Innovation Solution
A soft capsule formulation comprising a shell made of gelatin, glycerol, and sorbitol, encapsulating a pharmaceutical composition of calcifediol with medium chain triglycerides, isopropyl myristate, and pharmaceutically acceptable solvents, devoid of waxes, forms self-emulsifying drug delivery systems (SEDDS) for improved bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If calcifediol is formulated as an immediate release oral preparation, then the convenience of administration is improved, but the oral bioavailability deteriorates due to poor water solubility
Solution Approach 1:
The invention changes the physical and chemical parameters of the formulation by using self-emulsifying drug delivery systems (SEDDS) that transform the poorly water-soluble calcifediol into fine oil-in-water emulsions, microemulsions, or nanoemulsions upon contact with gastrointestinal fluids, thereby improving dissolution and bioavailability while maintaining immediate release characteristics
Solution Approach 2:
The invention employs composite formulations combining calcifediol with specific oils, surfactants, solvents, and co-solvents in defined ratios to create self-emulsifying systems that spontaneously form stable emulsions in the gastrointestinal tract, resolving the contradiction between immediate release convenience and bioavailability reliability
2Reliability
If calcifediol is provided as a liquid solution in medium chain triglyceride, then the oral bioavailability is improved, but the formulation complexity increases
Solution Approach 1:
The invention utilizes self-emulsifying drug delivery systems where the formulation automatically forms fine emulsions upon contact with gastrointestinal fluids through the natural motility of the stomach and intestine, eliminating the need for external emulsification equipment or complex processing steps while achieving improved bioavailability
3Duration of action of moving object
If waxes or releasable binding components are added to solid formulations, then the controlled release is achieved, but the immediate release property is lost
Solution Approach 1:
The invention extracts and eliminates waxes and other releasable binding components from the formulation, using instead a self-emulsifying system based on oils, surfactants, and solvents that provides immediate release while achieving controlled drug delivery through spontaneous emulsion formation in the gastrointestinal tract
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 soft capsule formulation enhances calcifediol's bioavailability by achieving a Cmax and AUC0-72 that are at least 1.2 times greater than existing liquid preparations, providing effective treatment and prevention of vitamin D deficiency-related diseases.
Implementation Method 1
self-emulsifying drug delivery systems (SEDDS). These systems are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants that rapidly and spontaneously form fine oil in water emulsions, microemulsions or nanoemulsions when introduced into aqueous phases under gentle agitation
Implementation Method 2
a pharmaceutically acceptable organic solvent selected from the group consisting of ethanol, isopropanol, propylene glycol, polyethylene glycol, benzyl alcohol and mixtures thereof
Data Source
Figure 1
AI summary
The present invention relates to calcifediol soft capsules, to their use in the treatment or prevention of diseases related to vitamin D deficiency, such as vitamin D deficiency, demineralization such as hypocalcemia and hypophosphatemia, renal osteodystrophy, rickets, osteoporosis, osteopenia, osteoarthritis, osteoarthrosis, osteomalacia, hypoparathyroidism, and inflammatory bowel disease, and to their process of manufacture.