title: Formulation optimization of a drug in adhesive transdermal analgesic patch.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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/cm2of CDB, while the CDB-APAP combination patch with 5% w/w OA delivered 151.40 µg/cm2CDB and 58.12 µg/cm2APAP in 24 h.
  
  
  CONCLUSIONS
  Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.
authors.affiliation: a Department of Pharmaceutical Sciences , College of Pharmacy, Mercer University , Atlanta , GA , USA.
authors.forename: Ranadheer
authors.initials: R
authors.lastname: Ravula
authors.affiliation: a Department of Pharmaceutical Sciences , College of Pharmacy, Mercer University , Atlanta , GA , USA.
authors.forename: Anushree K
authors.initials: AK
authors.lastname: Herwadkar
authors.affiliation: b University of the Arts London, London College of Fashion , London , UK , and.
authors.forename: Mehtab J
authors.initials: MJ
authors.lastname: Abla
authors.affiliation: c Little Innovations LLC , Knoxville , TN , USA.
authors.forename: John
authors.initials: J
authors.lastname: Little
authors.affiliation: a Department of Pharmaceutical Sciences , College of Pharmacy, Mercer University , Atlanta , GA , USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D002102:Cadaver; D002152:Calorimetry, Differential Scanning; D002648:Child; D002675:Child, Preschool; D003061:Codeine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003460:Crystallization; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007223:Infant; D059408:Pain Management / Q000379:methods*; D010539:Permeability; D012995:Solubility; D013552:Swine; D057968:Transdermal Patch
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004338:Drug Combinations; D000082:Acetaminophen; D006853:Hydrocodone; D003061:Codeine
keywords: Calorimetry (DSC); crystallization; formulation; microscopy; pediatric; permeation enhancers; skin; solubility