Prediction of Transdermal Flux of Prodrugs of 5‐Fluorouracil, Theophylline, and 6‐Mercaptopurine with a Series/Parallel Model

Roberts, William J.; Sloan, Kenneth B.

doi:10.1002/1520-6017(200011)89:11<1415::aid-jps5>3.0.co;2-t

Cited by 33 publications

(3 citation statements)

References 33 publications

(48 reference statements)

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“…A variety of quantitative structure-activity relationships to predict transdermal flux and permeability of drugs have been reported. [47][48][49][50][51] The simplest models to predict permeability across biological membranes are based on lipophilicity indicators such as octanol-water or hexadecane-water partition coefficients. The inclusion of other parameters such as molecular weight and hydrogen bonding has been shown to improve the predictive capabilities of the models.…”

Section: Permeability/flux Modelsmentioning

confidence: 99%

“…The mean maximum flux values of the carbamate prodrugs (Table II) were fit to the Roberts and Sloan equation 51 as well as modifications incorporating the relative cross-sectional area of the carbamate head-groups or the relative cross-sectional area scaled by molecular weight (MW) in place of MW. The cross-sectional areas of the head groups of the N-monoalkyl and N,N-dialkyl carbamate prodrugs measured using SYBYL® 6.8.1 software (Tripos Inc., St Louis, MO) are listed in Table III.…”

Section: Evaluation Of Modelsmentioning

confidence: 99%

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Human Skin Sermeation of 3-O-Alkyl Carbamate Prodrugs of Naltrexone

Vaddi

Banks

Chen

et al. 2009

Journal of Pharmaceutical Sciences

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N-Monoalkyl and N,N-dialkyl carbamate prodrugs of naltrexone (NTX), an opioid antagonist, were synthesized and their in vitro permeation across human skin was determined. Relevant physicochemical properties were also determined. Most prodrugs exhibited lower melting points, lower aqueous solubilities, and higher oil solubilities than NTX. The flux values from N-monoalkyl carbamate prodrugs were significantly higher than those from NTX and N,N-dialkyl carbamates. The melting points of N-monoalkyl carbamate prodrugs were quite low compared to the N,N-dialkyl carbamate prodrugs and NTX. Heats of fusion for the N,N-dialkyl carbamate prodrugs were higher than that for NTX. N-Monoalkyl carbamate prodrugs had higher stratum corneum/vehicle partition coefficients than their N,N-dialkyl counterparts. Higher percent prodrug bioconversion to NTX in skin appeared to be related to increased skin flux. N,N-Dialkyl carbamate prodrugs were more stable in buffer and in plasma than N-monoalkyl carbamate prodrugs. In conclusion, N-monoalkyl carbamate prodrugs of NTX improved the systemic delivery of NTX across human skin in vitro. N,N-Dialkyl substitution in the prodrug moiety decreased skin permeation and plasma hydrolysis to the parent drug. The cross-sectional area of the carbamate head group was the major determinant of flux of the N-monoalkyl and N,N-dialkyl carbamate prodrugs of NTX.

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Section: Permeability/flux Modelsmentioning

confidence: 99%

Section: Evaluation Of Modelsmentioning

confidence: 99%

Human Skin Sermeation of 3-O-Alkyl Carbamate Prodrugs of Naltrexone

Vaddi

Banks

Chen

et al. 2009

Journal of Pharmaceutical Sciences

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show abstract

“…This strategy is well established and has been developed to enable targeted drug delivery for oral therapeutics. Recently, this approach has also been applied to the transdermal drug delivery of, for example, ketorolac, 1 temozolomide, 2 5‐fluorouracil, 3 naltrexone 4 and morphine 5 . Captopril is well established as an oral therapeutic that could benefit from transdermal drug delivery via the prodrug strategy.…”

Section: Introductionmentioning

confidence: 99%