Formulation optimization of a drug in adhesive transdermal analgesic patch

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Dermatology

Background:

• Conventional pain management presents challenges like side effects and dosing difficulties.
• Transdermal analgesic patches offer a promising alternative to overcome these limitations.

Purpose of the Study:

• To formulate a drug-in-adhesive transdermal patch containing codeine (CDB) and acetaminophen (APAP) for moderate pain in children.
• To evaluate the permeation profiles of CDB and APAP across artificial and human skin models.

Main Methods:

• Screening of hydrocodone bitartrate, CDB, and APAP using slide crystallization and polarized light microscopy.
• Permeation studies utilizing vertical Franz diffusion cells across porcine ear skin, human skin, and epidermis.
• Quantification of drug permeation by high-performance liquid chromatography (HPLC).
• Preparation of transdermal patches by dissolving drugs in adhesive with or without oleic acid (OA).

Main Results:

• Codeine (CDB) exhibited superior permeation (660.21 µg/cm²) and the shortest lag time (4.35 ± 0.01 h) among the screened drugs.
• Optimal drug concentrations for patch formulation were determined: 40% of saturation solubility (Cs) for CDB and 200% of Cs for APAP.
• A CDB standalone patch delivered 105.48 µg/cm² of CDB.
• A CDB-APAP combination patch with 5% oleic acid delivered 151.40 µg/cm² CDB and 58.12 µg/cm² APAP within 24 hours.

Conclusions:

• Drug-in-adhesive transdermal patches containing CDB and APAP were successfully developed for pediatric use.
• The addition of oleic acid significantly enhanced the solubility and permeation of both CDB and APAP.
• These novel patches represent a viable alternative for managing moderate pain in infants and children.