Isothermal Crystallization Kinetics of Lidocaine in Supersaturated Lidocaine/Polyacrylate Pressure Sensitive Adhesive Systems

• Published in: Journal of pharmaceutical sciences 2005-09, Vol.94 (9), p.2039-2048
• Main Authors: Cui, Yong, Frank, Sylvan G.
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Crystallization; Diffusion; Drug Carriers - chemistry; Drug Stability; Duro-Tak; General pharmacology; isothermal calorimetry; Kinetics; lidocaine; Lidocaine - administration & dosage; Lidocaine - analogs & derivatives; Lidocaine - chemistry; Medical sciences; nucleation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pressure; pressure sensitive adhesive (PSA); Solubility; Solutions - chemistry; supersaturation; Thermodynamics; Tissue Adhesives - chemistry; transdermal drug delivery; Transition Temperature
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20339

Isothermal crystallization of lidocaine (LC) in supersaturated LC/Duro-Tak® 87-2287 (DT2287) polyacrylate pressure sensitive adhesive (PSA) systems has been studied by differential scanning calorimetry (DSC). It was found that crystallization of LC in supersaturated LC/DT2287 systems was governed by the nucleation process, which in turn was dependent on temperature and composition of the systems. A critical temperature Tcrit was found at ∼26°C, above which the crystallization of LC in LC/DT2287 systems becomes slow. The lack of dependence of Tcrit on the composition of the mixtures indicates that the presence of the PSA affected the kinetics (diffusion) rather than the thermodynamics of the nucleation process. A critical degree of saturation Scrit of ∼4 was also found, above which the nucleation rate sharply increases. Kinetic analysis based on the classical theory of nucleation indicates that nucleation of LC in the PSA medium is a diffusion-controlled process. The activation energy of crystallization had a two-phase dependence on temperature suggesting that the mechanism of crystallization may change at the transition temperatures. As the weight fraction of LC increased in the systems, the activation energy of crystallization, ΔGc, was minimal at ∼15°C, indicating that the nucleation of LC in the LC/DT2287 systems is at its fastest rate around this temperature. These fundamental analyses of nucleation and crystallization mechanisms are of practical significance in the design of supersaturated drug delivery systems. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.