Fujicalin®: Revolutionizing Axitinib Delivery with Liquisolid Technology
Introduction
Axitinib (AXT), a second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR), is used in the treatment of advanced renal cell carcinoma (RCC). Despite its efficacy, AXT’s clinical application is limited by its poor aqueous solubility and bioavailability, which stands at approximately 58%.
To address these challenges, the present study explores the use of liquisolid (LS) technology, particularly focusing on Fujicalin® SG. Fujicalin® a synthetic, highly porous, less abrasive,smooth, spherical, and free flowing spherically granulated Dibasic Calcium Phosphate Anhydrous (DCPA) with superior liquid retention / adsorption capabilities, is investigated as a means of enhancing AXT’s dissolution and bioavailability for the treatment of advanced renal cell carcinoma (RCC).
This newsletter presents a detailed overview of the methodology, results, and implicationsof using Fujicalin® in enhancing the dissolution and bioavailability of AXT.
Problem: Poor Solubility and Bioavailability of Axitinib
Axitinib (AXT) faces limitations in its clinical application due to its poor aqueous solubility and bioavailability, which is only about 58%. This low bioavailability restricts its absorption in the body, preventing the drug from reaching effective therapeutic levels. As a result, its potential to effectively target and treat advanced renal cell carcinoma (RCC) is compromised.
How To Solve
To solve the problem of poor solubility and low bioavailability, the study investigates using Fujicalin® SG in Liquisolid technology to improve the solubility and bioavailability of Axitinib (AXT). Fujicalin® SG enhances dissolution and absorption due to its superior liquid retention and adsorption properties, significantly increasing AXT’s bioavailability and therapeutic effectiveness.
Methodology
The study utilized a 3 full factorial design to optimize the formulation parameters for AXT LS compacts. The key components included:
- Fujicalin® SG: Serves as the primary carrier
- Aerosil® 200: Used as the coating material
- PEG 200: Acts as the non-volatile solvent
Solubility Analysis
AXT was dissolved in various non-volatile solvents to determine its solubility profile. The solubility was assessed by creating supersaturated solutions and measuring the concentration spectrophotometrically at a wavelength of 330 nm.
Preparation of Liquisolid Systems
Optimal flowable liquid-retention potential determination:
- ɸ-value: Represents a powder’s maximum liquid retention while maintaining flowability.
- Method: Angle of slide determination using PEG 200.
- ɸ-value corresponding to a θ of 33° represents optimal flowable liquid retention.
Determination of liquid load factors
- Liquid retention in a LS system depends on the excipient ratio (R), the ratio of carrier (Q) to coating material (q).
- Adequate flow and compression are achieved by controlling the liquid load on the carrier. This liquid load is quantified by the liquid load factor (Lf), defined as the ratio of drug solution weight (W) to carrier weight (Q) (Lf = W/Q).
- Lf can also be calculated using the flowable values (ɸ and $) of the carrier and coating materials, respectively (Lf = ɸ + $ x 1/R)
Preparation of liquisolid system
- LS formulations of AXT were prepared using PEG 200 as the liquid vehicle (5-15% w/w) and excipient ratios (R) of 10-30, guided by carrier and coating material values. A three-phase blending process was employed:
First Phase
Mixing of AXT solution with carrier/coating (1 r.p.s., 1 min)
Second Phase
Uniform outspread of LS powder as an even film on mortar surface and facilitate absorption of AXT solution within the pores of powder particles.
Third Phase
Addition of 8% w/w sodium starch glycolate
- Specific formulations (LS1-LS9) were compressed using appropriate punch sizes to achieve target weights (e.g., 1012 mg for LS1 using a 13mm punch).
- Direct compression tablets (DCT) were prepared by directly compressing a 100:5 carrier:coating mixture containing 5mg AXT.
Characterization Techniques
The resulting LS compacts were characterized using several techniques:
- P-XRD (Powder X-Ray Diffraction)
- DSC (Differential Scanning Calorimetry)
- SEM (Scanning Electron Microscopy)
- In Vitro Drug Dissolution Studies
Cytotoxicity and Bioavailability Studies
In vitro cytotoxicity was evaluated using A498 cell lines, while bioavailability studies were conducted on New Zealand rabbits to assess systemic availability.
Results: Significant Improvement in Dissolution and Bioavailability
Dissolution Improvement: The optimized LS formulation (LS6) exhibited over 99% dissolution within a specified timeframe, compared to just 18.05% dissolution from Directly Compressed Tablets (DCT).
Bioavailability Enhancement: The LS formulation demonstrated a 2.03-fold increase in oral bioavailability compared to AXT dispersion.
Cytotoxicity Findings: The LS formulation showed superior cytotoxic effects, with a 1.75-fold increase in apoptosis rate, suggesting enhanced therapeutic efficacy.
Continue reading and see the full Pharmaceutical Technical Newsletter on Fujicalin®: Revolutionizing Axitinib Delivery with Liquisolid Technology here:
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Summary
Fujicalin® SG, in combination with Liquisolid technology, significantly enhances the dissolution rate and bioavailability of Axitinib, addressing the solubility challenges associated with the drug. This improvement can lead to better clinical outcomes for RCC treatment, potentially reducing side effects and improving patient quality of life. The technology also holds promise for the formulation of other poorly soluble drugs.
For more details on how Fujicalin® can improve your formulations, contact us via the form below.
Source: Fuji Chemical Industries technical newsletter Fujicalin®: Revolutionizing Axitinib Delivery with Liquisolid Technology
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