SOP for Formation of Solid Lipid Nanoparticles (SLNs)

Standard Operating Procedure for Formation of Solid Lipid Nanoparticles (SLNs)

1) Purpose

The purpose of this SOP is to outline the procedure for the preparation of solid lipid nanoparticles (SLNs). SLNs are colloidal carriers made from solid lipids, offering controlled drug release and enhanced bioavailability for various pharmaceutical and cosmetic applications.

2) Scope

This SOP applies to personnel involved in the formulation, characterization, and optimization of solid lipid nanoparticles for drug delivery and related research.

3) Responsibilities

Operators: Responsible for preparing SLNs according to the outlined procedure and ensuring they meet the required specifications.
QA: Responsible for verifying that SLNs meet the defined standards for particle size, encapsulation efficiency, stability, and drug release.

4) Procedure

4.1 Selection of Lipids and Surfactants

4.1.1 Lipid Selection

4.1.1.1 Select solid lipids such as stearic acid, glyceryl monostearate, or cetyl palmitate, which remain solid at room temperature and physiological temperature to ensure controlled drug release.

4.1.2 Surfactant Selection

4.1.2.1 Choose appropriate surfactants (e.g., Tween 80, Poloxamer 188) to stabilize the SLNs and prevent aggregation during the formulation process.

4.2 Nanoparticle Preparation

4.2.1 Hot Homogenization Method

4.2.1.1 Heat the lipid phase to approximately 5–10°C above the melting point of the lipid. Dissolve the drug in the molten lipid if required.
4.2.1.2 Prepare the aqueous phase

by dissolving the surfactant in distilled water, heating it to the same temperature as the lipid phase.

4.2.1.3 Mix the lipid phase into the aqueous phase under continuous stirring and perform high-pressure homogenization to create the nanoparticle suspension.

4.2.2 Cold Homogenization Method (Alternative)

4.2.2.1 Melt the lipid phase, incorporate the drug, and rapidly cool the lipid using liquid nitrogen or dry ice to form a solid lipid matrix.
4.2.2.2 Mill the solid lipid matrix into microparticles and then disperse them in an aqueous surfactant solution, followed by high-pressure homogenization at room temperature.

4.3 Characterization and Testing

4.3.1 Particle Size and Surface Charge

4.3.1.1 Measure the particle size and polydispersity index (PDI) using dynamic light scattering (DLS) to ensure that the SLNs are within the desired size range (50–500 nm) for drug delivery.
4.3.1.2 Determine the surface charge (zeta potential) to confirm colloidal stability.

4.3.2 Encapsulation Efficiency

4.3.2.1 Quantify the amount of drug encapsulated in the SLNs using techniques such as UV-Vis spectrophotometry or high-performance liquid chromatography (HPLC) and calculate the encapsulation efficiency.

4.3.3 In Vitro Drug Release

4.3.3.1 Perform in vitro drug release studies using simulated body fluids (e.g., phosphate-buffered saline, pH 7.4) to evaluate the release profile of the drug from the SLNs.

4.4 Optimization and Stability

4.4.1 Process Optimization

4.4.1.1 Optimize the process parameters (e.g., homogenization pressure, number of cycles, surfactant concentration) to achieve the desired particle size and drug release characteristics.

4.4.2 Stability Testing

4.4.2.1 Conduct stability testing under various conditions (e.g., temperature, light exposure) to ensure that the SLNs maintain their size, drug loading, and colloidal stability over time.

4.5 Sterility and Storage

4.5.1 Sterility

4.5.1.1 If required, sterilize the SLN suspension by filtration using a 0.22 µm filter to remove microbial contaminants.

4.5.2 Storage Conditions

4.5.2.1 Store the SLNs in sealed, sterile containers at 4°C or room temperature based on the stability data obtained.

5) Abbreviations, if any

SLNs: Solid Lipid Nanoparticles
DLS: Dynamic Light Scattering
HPLC: High-Performance Liquid Chromatography
PDI: Polydispersity Index

6) Documents, if any

SLN Formulation Logbook

7) References, if any

Guidelines for Solid Lipid Nanoparticle Formulation
FDA Guidance on Nanotechnology in Pharmaceuticals

8) SOP Version

Version 1.0

Annexure

SLN Formulation Logbook Template


  
    Date
    Batch Number
    Lipid Used
    Surfactant Used
    Particle Size
    Encapsulation Efficiency
    Operator Initials
    QA Initials
  
  
    DD/MM/YYYY
    Batch Number
    Lipid Name
    Surfactant Name
    Size in nm
    Efficiency (%)
    Operator Name
    QA Name