Formulation optimization of a drug in adhesive transdermal analgesic patch.

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/cm(2)), 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/cm(2) of CDB, while the CDB-APAP combination patch with 5% w/w OA delivered 151.40 µg/cm(2) CDB and 58.12 µg/cm(2) 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.

Formulation optimization of a drug in adhesive transdermal analgesic patch.

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.

Transdermal delivery of methotrexate for pediatrics using silicon microneedles.

BACKGROUND: The objective of this work was to study transdermal delivery of methotrexate using silicon microneedles and simulate plasma concentrations using a population pharmacokinetic model. RESULTS: Characterization of silicon microneedles was carried out by scanning electron microscopy, transepidermal water loss, methylene blue staining, calcein imaging, pore permeability index and confocal microscopy, which confirmed the formation of microchannels. In vitro permeation studies were performed to study the enhancement in transdermal delivery following microporation. CONCLUSION: Simulation data demonstrated that with 16, 64, 128 and 192 microneedles, mean plasma concentrations of 0.3, 1.4, 2.8 and 4.2 ng/ml, respectively, can be achieved. Thus, therapeutically relevant doses could be delivered in pediatrics by increasing the number of microneedles and patch area.