Pheroid technology for the transdermal delivery of lidocaine and prilocaine

Abstract

Local anaesthetics have been implemented extensively in the case of a variety of painful superficial procedures, venipuncture, skin graft harvesting, anal or genital pruritus, poison ivy rashes, postherpetic neuralgia and several other dermatoses. The dilemma with commercially available local acting anaesthetics is that it may take well up to an hour to produce an anaesthetic effect. Anaesthetics have to traverse the highly efficient barrier, the stratum corneum, in order to reach the intended target site which is the free nerve endings located in the dermis. The objective of this study was to compare the transdermal delivery of an eutectic combination of two ionisable amide types of local anaesthetics, lidocaine HCI and prilocaine HCI, delivered with the novel Pheroid™ technology to that of a commercially available product in order to establish whether the lag time could be significantly reduced. Several techniques of promoting the penetration of these anaesthetics have previously been employed, including occlusive dressing, entrapment in liposomes and miscelles, iontophoretic delivery and so forth. The Pheroid™ delivery system is novel technology that entails improved delivery of several active compounds. It is a submicron emulsion type formulation that possesses the ability to be transformed in morphology and size, thereby affording it tremendous flexibility. Since it primarily consists of unsaturated essential fatty acids, it is not seen as foreign to the body but rather as a skin-friendly carrier. Vertical Franz cell diffusion studies were performed over a 12 hour period using Caucasian female abdominal skin obtained, with the consent of the donor, from abdominoplastic surgery. Comparison was made between the commercial product EMLA® cream, the active local anaesthetics dissolved in phosphate buffered solution (PBS) and the active ingredients entrapped within Pheroid™ vesicles. Distinct entrapment could be ascertained visually by confocal laser scanning microscopy (CLSM). The amount of drug that traversed the epidermal membrane into the receptor phase was then assayed by high performance liquid chromatography (HPLC). The results obtained with the Pheroid™ vesicles revealed a biphasic character with rapid permeation during the first two hours, followed by a plateau between 3 to 12 hours. The initial dramatic increase in percentage yield and flux indicates that the Pheroid™ carrier enhances the transdermal delivery of the actives in order to accelerate the onset of action.