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European Journal of Applied Sciences – Vol. 11, No. 3

Publication Date: June 25, 2023

DOI:10.14738/aivp.113.14907

Peña-Velasco, G., Amador-González, E., Melgoza-Contreras, L. M., & Hernández-Baltazar, E. (2023). Assessment of Topical

Formulations Skin Permeation Using Raman Spectroscopy. European Journal of Applied Sciences, Vol - 11(3). 793-804.

Services for Science and Education – United Kingdom

Assessment of Topical Formulations Skin Permeation Using

Raman Spectroscopy

Peña-Velasco, Gabriela

Universidad Autó nóma del Estadó de Mórelós,

Facultad de Farmacia, Cuernavaca, Mórelós

Amador-González, Enrique

Universidad Naciónal Autó nóma de Me xicó,

Facultad de Quí mica, Me xicó

Melgoza-Contreras, Luz María

Universidad Autó nóma Metrópólitana,

Departamentó de Ciencias Bióló gicas, Me xicó

Hernández-Baltazar, Efrén

Universidad Autó nóma del Estadó de Mórelós,

Facultad de Farmacia, Cuernavaca, Mórelós

GRAPHICAL ABSTRACT

ABSTRACT

The use of new noninvasive analytical techniques and procedures for the

assessment of topical formulation skin permeation has been a challenge for

pharmaceutics sciences. In recent years, Raman spectroscopy has been limited to

the identification of components inside a sample or unknown substances. In this

work, a handheld Raman spectrometer was used in the follow-up of active

pharmaceutical ingredients (APIs) in topical formulations. Thus, in combination

with Franz cells and Tape stripping procedures, permeation flux and retained drug

amount in layers of skin were evaluated in hydrogels of lidocaine (LD) and

meloxicam (MX) with myristate isopropyl (IPM). The proposed method allows

lower analysis time, simple operation, collects direct measures of APIs without

preview sample treatment, and avoids the use of solvents in support of eco-friendly.

Diagrama Descripción generada automáticamente

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Peña-Velasco, G., Amador-González, E., Melgoza-Contreras, L. M., & Hernández-Baltazar, E. (2023). Assessment of Topical Formulations Skin

Permeation Using Raman Spectroscopy. European Journal of Applied Sciences, Vol - 11(3). 793-804.

URL: http://dx.doi.org/10.14738/aivp.113.14907

Table 1 Properties of model drugs for hydrogel formulations.

Lidocaine Hydrochloride Meloxicam

Molecular weight (g/mol) 270.8 351.4

pka 7.7 4.08

LogP 2.44 3.54

Solubility (mg/mL at 25°C) 50 < 0.1

TPSA (Å2) 32.3 136

LogP = octanol-water partition coefficient, TPSA= Topological Polar Surface Area

Methods

Preparation of Hydrogels:

Two different formulations of LD and MX hydrogels were prepared and evaluated, respectively

(with and without IPM added in them). Table 2 shows the composition of each formulation.

Finally, the prepared hydrogels in an amber glass recipient at room temperature for 24 h before

use were stored. The fabricated hydrogels were labeled as LD and MX for lidocaine and

meloxicam hydrogel, respectively, the formulations with IPM added were identified as LD-IPM

and MX-IPM, respectively.

Table 2 Composition of prepared lidocaine and meloxicam hydrogels formulations.

LD Hydrogel LD-IPM

Hydrogel

MX

Hydrogel

MX-IPM

Hydrogel

Carboxymethylcellulose sodium (2%) * * * *

Glycerin (10%) * * * *

Meloxicam (0.3%) * *

Lidocaine hydrochloride (10%) * *

IPM (1%) * *

Water q.s. 100 mL 100 mL 100 mL 100 mL

Procedure for the Obtention of Skin Membrane:

Used the test No. 428: Skin absorption: in vitro method from the Guidelines for the Testing of

Chemicals [10], skin from human or animal sources can be used and it is essential that skin is

properly prepared [11]. Pig skin has been reported with similar features to human beings,

making it a suitable animal model for permeation tests [8]. Therefore, excised skin ear pig

dorsal surface was used, purchased from the slaughterhouse in Cuernavaca, Morelos, México.

Briefly, the pig skin membrane was prepared as previously reported [9], a first step of cleaning

with distilled water, for removing traces of dirt, blood, and/or others. The membrane skin was

extracted manually with a scalpel, separating the subcutaneous fatty layer from the skin

(extracting the dermis without subcutaneous tissue) leaving the stratum corneum intact. The

skin membrane obtained and conditioned with phosphate‐buffered saline (PBS pH 7.4) was

stóred at −20 °C until use.

Franz Diffusion Cell Permeation Studies:

Vertical Franz-type diffusion cells with an average area and volume of 3.31 cm2 and 24.84 cm3

were used. Therefore, skin pig circular samples of around 3.31 cm2 were placed between the

donor and receiver chamber of a Franz cell, with the stratum corneum facing the donor

chamber. The receptor compartment was filled with 25 ml of phosphate-buffered saline (pH