Surface enhanced Raman scattering microtips for microenvironment pH determination of semi-solid preparations.

Area of Science:

• Materials Science
• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Semi-solid preparations (ointments, creams, gels) are complex topical dosage forms.
• pH is a critical quality attribute influencing formulation properties and drug efficacy.
• Traditional pH measurement methods lack spatial resolution and accuracy for microenvironments.

Purpose of the Study:

• To develop pH-sensitive surface-enhanced Raman scattering (SERS) microtips for localized pH detection.
• To assess the microenvironment pH of various semi-solid topical preparations.
• To introduce a novel tool for enhanced quality control and formulation development.

Main Methods:

• Fabrication of SERS microtips using glass needles (approx. 1 μm tip size) with *in situ* grown gold nanoparticles (Au NPs).
• Immobilization of 4-mercaptopyridine, a pH-sensitive Raman reporter, onto Au NPs for pH sensing (pH range 3-10).
• Application of SERS microtips for localized pH measurements in commercial ointments and gels, and *in vivo* monitoring on mice.

Main Results:

• SERS microtips demonstrated characteristic Raman peak shifts correlating with pH changes.
• Localized pH measurements in 15 commercial ointments and 8 gels revealed microenvironment differentiation.
• Successful *in vivo* monitoring of pH changes in ointment applied to localized wounds on live mice.

Conclusions:

• Developed pH-sensitive SERS microtips provide a highly sensitive tool for localized pH detection in semi-solid preparations.
• This method offers superior spatial resolution and microenvironment differentiation compared to conventional pH meters.
• The SERS microtips represent a significant advancement for the quality assessment and prescription optimization of topical semi-solid formulations.