کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8414113 1545344 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Iontophoretic transport kinetics of ketorolac in vitro and in vivo: Demonstrating local enhanced topical drug delivery to muscle
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Iontophoretic transport kinetics of ketorolac in vitro and in vivo: Demonstrating local enhanced topical drug delivery to muscle
چکیده انگلیسی
The objective of the study was to investigate the iontophoretic delivery kinetics of ketorolac (KT), a highly potent NSAID and peripherally-acting analgesic that is currently indicated to treat moderate to severe acute pain. It was envisaged that, depending on the amounts delivered, transdermal iontophoretic administration might have two distinct therapeutic applications: (i) more effective and faster local therapy with shorter onset times (e.g. to treat trauma-related pain/inflammation in muscle) or (ii) a non-parenteral, gastrointestinal tract sparing approach for systemic pain relief. The first part of the study investigated the effect of experimental conditions on KT iontophoresis using porcine and human skin in vitro. These results demonstrated that KT electrotransport was linearly dependent on current density - from 0.1875 to 0.5 mA/cm2 - (r2 > 0.99) and drug concentration - from 5 to 20 mg/ml (r2 > 0.99). Iontophoretic permeation of KT from a 2% hydroxymethyl cellulose gel was comparable to that from an aqueous solution with equivalent drug loading (584.59 ± 114.67 and 462.05 ± 66.56 μg/cm2, respectively). Cumulative permeation (462.05 ± 66.56 and 416.28 ± 95.71 μg/cm2) and steady state flux (106.72 ± 11.70 and 94.28 ± 15.47 μg/cm2 h), across porcine and human skin, were statistically equivalent confirming the validity of the model. Based on the results in vitro, it was decided to focus on topical rather than systemic applications of KT iontophoresis in vivo. Subsequent experiments, in male Wistar rats, investigated the local enhancement of KT delivery to muscle by iontophoresis. Drug biodistribution was assessed in skin, in the biceps femoris muscle beneath the site of iontophoresis ('treated muscle'; TM), in the contralateral muscle ('non-treated muscle'; NTM) and in plasma (P). Passive topical delivery and oral administration served as negative and positive controls, respectively. Iontophoretic administration for 30 min was superior to passive topical delivery for 1 h and resulted in statistically significant increases in KT levels in the skin (91.04 ± 15.48 vs. 20.16 ± 8.58 μg/cm2), in the biceps femoris at the treatment site (TM; 6.74 ± 3.80 vs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 86, Issue 2, February 2014, Pages 219-226
نویسندگان
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