Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Biomedical Engineering

Background:

• Poor aqueous solubility of drug candidates hinders oral drug development.
• In situ amorphization within a polymeric network offers an alternative to conventional amorphous solid dispersions.
• Existing methods face challenges like low drug loading, excipient toxicity, and drug degradation.

Purpose of the Study:

• To investigate the use of magnetic hyperthermia with superparamagnetic iron oxide nanoparticles (SPIONs) for in situ amorphization of celecoxib in oral tablets.
• To optimize SPION composition, content, drug load, and alternating magnetic field (AMF) exposure duration for effective amorphization.
• To evaluate the toxicity and solubility enhancement of the in situ amorphized drug.

Main Methods:

• Doped SPIONs (Zn_0.5Fe_2.5O₄ and Mn_0.5Fe_2.5O₄) were produced via flame spray pyrolysis.
• Tablets were fabricated by compacting SPIONs with polyvinylpyrrolidone and celecoxib.
• A design of experiments approach was employed to study the effects of SPION type, content, drug load, and AMF duration on amorphization.
• Drug amorphization was correlated with maximum tablet temperature.

Main Results:

• The degree of celecoxib amorphization strongly correlated with the maximum tablet temperature (r = 0.96).
• Complete amorphization was achieved using 20 wt % Mn_0.5Fe_2.5O₄ and 30 wt % celecoxib, reaching 165.2 °C after 15 min of AMF exposure.
• Manganese ferrite SPIONs showed no toxicity in Caco-2 cell lines.
• In situ amorphized celecoxib exhibited a 5-fold increase in solubility in biorelevant intestinal fluid compared to crystalline celecoxib.

Conclusions:

• SPIONs can be effectively utilized as enabling excipients for magnetic hyperthermia-induced in situ amorphization in oral dosage forms.
• This approach overcomes the solubility limitations of poorly soluble drugs, enhancing their bioavailability.
• The developed method offers a promising strategy for improving oral drug delivery.