Formulation optimization of a drug in adhesive transdermal analgesic patch

Abstract

Context: Conventional pain management approaches have limitations such as gastrointestinal side effects, frequent dosing, and difficulties in swallowing medications. Hence, to overcome these limitations, we developed a transdermal analgesic patch.

Objective: This study was designed to formulate a drug in adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may potentially treat moderate pain in children.

Materials and methods: Three analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide crystallization study using polarized light microscope and their permeation profiles were studied using vertical Franz diffusion cells across porcine ear skin, dermatomed human skin and epidermis for 24 h, and the samples were quantified by high performance liquid chromatography. Patches used for permeation studies were prepared by dissolving sub-saturation concentration of the drug(s) in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting knife.

Results and discussion: Among the three drugs screened, CDB demonstrated the best permeation profile (660.21 µg/cm²), and shortest lag time (4.35 ± 0.01 h), and hence was chosen for patch studies. The highest concentration of CDB in the patch at which drug does not crystallize was determined as 40% of its saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB standalone patch delivered 105.48 µg/cm² of CDB, while the CDB–APAP combination patch with 5% w/w OA delivered 151.40 µg/cm² CDB and 58.12 µg/cm² APAP in 24 h.

Conclusion: Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.

• Calorimetry (DSC)
• crystallization
• formulation
• microscopy
• pediatric
• permeation enhancers
• skin
• solubility

Acknowledgements

Our thanks are due to Dr. Piyush Jain, Dr. Vishal Sachdeva, Dr. Meera Gujjar, Arunprasad Sivaraman, and Pavilion Compounding Pharmacy, Atlanta, GA, for their assistance to our research.

Declaration of interest

This project was supported by Little Innovations LLC., Knoxville, TN. The authors report no conflicts of interest. The authors are solely responsible for the contents of the article.