Effect of Salt Form on Gelation and Drug Delivery Properties of Diclofenac-Loaded Poloxamer Gels for Delivery to Impaired Skin.

PURPOSE: Treating chronic wounds is a significant clinical challenge, and a topical product would be ideal for pain management. Poloxamer 407, a thermosensitive polymer, would allow an analgesic drug to be topically applied to a wound as a liquid that transitions to a gel at physiologic temperature. Using diclofenac as a model analgesic drug, our goal was to determine effects of salt form on poloxamer gelation and drug delivery from poloxamer gels applied to excised skin with impaired barrier function. METHODS: Gelation properties of 17% and 20% poloxamer gels loaded with 0.4 to 1.7% diclofenac sodium, potassium, epolamine, or diethylamine were evaluated rheologically. Drug release and delivery were quantified using cellulose membranes, porcine skin, and tape-stripped porcine skin. RESULTS: Poloxamer gelation temperature increased with higher diclofenac concentration, regardless of salt form; the magnitude of increase varied in the following order: sodium>potassium>diethylamine>epolamine. Gelation temperature differences resulting from the various counterions generally matched previously observed trends of ion-specific effects on macromolecule solubility (the Hofmeister series). Despite changes in gelation behavior, we observed minimal corresponding effects on drug release or delivery. There were no significant differences in diclofenac released or delivered through intact porcine skin over 48 h. However, in studies with impaired (tape-stripped) skin, diclofenac delivery was slowest overall with the epolamine salt. CONCLUSION: Varying the salt form of a model analgesic drug can impact gelation and drug delivery characteristics of poloxamer systems. Further study of the mechanisms of these changes will be important for continued development of topical poloxamer products for clinical wound care.

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia.

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.