Solid lipid nanoparticle alginate bead system for fenoprofen release

Abstract

A system for the production of fenoprofen calcium-loaded solid lipid nanoparticles, comprising units for organic phase production, emulsification, homogenization and solvent extraction, configured to produce nanoparticles with controlled size and encapsulation efficiency.

Description

Field of invention

[0001] The invention relates to a system for the production of fenoprofen-calcium formulations with delayed drug release. In this system, solid lipid nanoparticles are embedded in alginate beads to improve bioavailability and enable controlled drug release. Background of the invention

[0002] Fenoprofen calcium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for the treatment of pain and inflammation. However, its clinical efficacy is limited by its short half-life, frequent dosing, and fluctuations in plasma concentration. Delayed-release systems can overcome these drawbacks. Conventional matrix tablets and capsules, however, often exhibit an initial release spike, low encapsulation efficiency, and inadequate control of drug diffusion. Solid lipid nanoparticles (SLNs) have emerged as promising carriers due to their biocompatibility, stabilization of lipophilic drugs, and ability to improve encapsulation efficiency. Alginate-based beads are known for their swelling capacity, mucoadhesiveness, and potential for ionic cross-linking, thereby enabling controlled drug release.However, combining SLNs with alginate beads requires precise coordination of the solvent removal, emulsification, and crosslinking steps to achieve optimal particle size, encapsulation, and delayed release. Therefore, there is a need for an integrated system for producing SLN-loaded alginate beads with high swelling capacity, reduced initial release surge, and prolonged drug release. Summary of the invention

[0003] The invention provides a system for the development of solid lipid nanoparticles embedded in alginate beads for the delayed release of fenoprofen calcium. The system integrates the preparation of the organic phase, nanoemulsion formation, solvent evaporation, and nanoparticle characterization into a controlled workflow. Fenoprofen calcium is dissolved in an organic solvent containing glyceryl monostearate and subsequently emulsified with an aqueous solution containing stabilizers. Homogenization under controlled stirring yields a nanoemulsion which, upon solvent evaporation, forms solid lipid nanoparticles with the desired particle size, polydispersity, and encapsulation efficiency.

[0004] In the next step, these optimized nanoparticles are dispersed in a sodium alginate matrix containing calcium carbonate and acetic acid. This leads to the in-situ release of crosslinking ions. By dropwise introducing the dispersion into a calcium chloride solution, ionically crosslinked spheres are formed, encapsulating the nanoparticles. The spheres are dried to obtain a stable, delayed-release system exhibiting a high swelling index and a gradual drug release of over 80% within 24 hours. The invention ensures improved stability, enhanced therapeutic efficacy, and reduced initial drug release. Detailed description

[0005] The system includes a module for the production of the organic phase, in which fenoprofen calcium is dissolved with glyceryl monostearate in dichloromethane to obtain a homogeneous lipid-drug solution. This organic phase forms the basis for SLN formation by encapsulating the drug in a lipid matrix. In parallel, an aqueous phase of polyvinyl alcohol and Span 20 is produced, which serves as an emulsifying medium and stabilizes the nanodroplets during homogenization.

[0006] The organic phase is gradually introduced into the aqueous phase under continuous stirring to form a coarse emulsion. A homogenization unit is then used to reduce the droplet size and transform the mixture into a nanoemulsion. Controlled stirring speed and duration ensure that the lipid droplets exhibit a narrow size distribution. Solvent evaporation is carried out under controlled conditions to completely remove the dichloromethane. This process yields solid lipid nanoparticles encapsulating fenoprofen calcium.

[0007] The formed nanoparticles are collected and characterized with respect to key parameters such as particle size, polydispersity index, and encapsulation efficiency to ensure consistent batch quality and therapeutic efficacy. The optimized nanoparticles typically achieve a defined nanometer range suitable for controlled-release drug applications.

[0008] In the bead formulation, the SLNs are dispersed in a sodium alginate solution containing calcium carbonate. The addition of acetic acid initiates the controlled release of ions from the calcium carbonate, which promotes the formation of a uniform gel matrix during bead fabrication. The SLN-alginate dispersion is then immersed in a calcium chloride bath, where immediate ionic cross-linking occurs. This results in the formation of spherical beads that encapsulate the nanoparticles.

[0009] After crosslinking, the beads are collected and subjected to controlled drying conditions to stabilize their structure. This drying process reduces surface moisture while maintaining the internal porosity, which is crucial for swelling behavior and the kinetics of delayed drug release. The beads exhibit a swelling index of over 120%, enabling controlled hydration and stepwise drug delivery.

[0010] The drug is released from the beads through a combination of diffusion from the lipid matrix and relaxation of the alginate gel network. This dual control mechanism enables sustained release for over 24 hours, with more than 80% of the drug being released in a controlled manner. The system minimizes the initial drug surge and prolongs the drug's residence time, thereby improving therapeutic outcomes in pain and inflammation management.

[0011] Overall, the invention provides an integrated manufacturing system that produces stable, biocompatible, SLN-loaded alginate beads and ensures controlled release, high encapsulation efficiency, and prolonged effectiveness.

Claims

[1] A system for the production of fenoprofen calcium-loaded solid lipid nanoparticles, comprising units for organic phase production, emulsification, homogenization and solvent extraction configured to produce nanoparticles with controlled size and encapsulation efficiency. [2] System according to claim 1, wherein the nanoparticles are embedded in a sodium alginate matrix containing calcium carbonate and acetic acid to form ionically cross-linked beads upon contact with calcium chloride solution. [3] System according to claim 1, wherein the resulting SLN alginate beads have a high swelling capacity and enable a sustained release of the active ingredient for more than 24 hours. [4] A controlled-release formulation containing the SLN alginate beads produced according to the system of claim 1, for improving the bioavailability and therapeutic efficacy of fenoprofen calcium.