Skin Penetration of Topical Formulations of Ibuprofen 5%: An in vitro Comparative Study

Abstract

An in vitro isolated human skin technique with known reliable predictive value for in vivo performance was used to compare the skin penetration of the proprietary ibuprofen gel formulation, Ibugel^TM, with five other commercially available topical formulations containing ibuprofen 5%: Ibuspray^TM, Ibumousse^TM, Proflex Cream^TM, Fenbid Gel^TM and Deep Relief Gel^TM. There was a marked difference between some formulations in the percentage of applied ibuprofen penetrating the skin samples, with Ibuspray^TM, Ibugel^TM and Ibumousse^TM showing the most efficient penetration. The percentage of applied ibuprofen penetrating the skin samples from these formulations was significantly greater (p < 0.05) at all sampling intervals when compared with Proflex Cream^TM, Fenbid Gel^TM or Deep Relief Gel^TM. By 48 h, the percentage of applied ibuprofen that had penetrated through the skin samples from Ibuspray^TM, Ibugel^TM and Ibumousse^TM was approximately 2.5 times greater than that from Deep Relief Gel^TM, 3 times greater than that from Proflex Cream^TM and 5 times greater than that from Fenbid Gel^TM. The data demonstrate that, with topically applied preparations, the composition of the vehicle can have a significant impact on the percutaneous penetration of the active medicament. The possible reasons for this are discussed in terms of partition and diffusion phenomena. Different topical presentations of the same drug substance – especially agents like ibuprofen which are intended for subcutaneous action – cannot be assumed to be pharmaceutically and clinically equivalent or indeed interchangeable.

Influence of Ethanol on the Solubility, Ionization and Permeation Characteristics of Ibuprofen in Silicone and Human Skin

“…We have previously evaluated the skin penetration of topical formulations of ibuprofen and we have shown that the composition of the vehicles can have a significant impact on the percutaneous penetration of the drug [2,[24][25][26][27] . A typical cream formulation may contain up to 10% of a cosolvent which can alter the pK a of a weak acid or a weak base and change thereby its solubility and partitioning behaviour.…”

“…Ibuprofen is one of the most widely available non-steroidal anti-inflammatory drugs for the management of inflammation and is available in both gel and cream formulations. Although the permeation of ibuprofen has been studied from a range of vehicles [2] , there has been, to our knowledge, no systematic investigation into the manner in which formulation components such as cosolvents may influence the ionization and permeability of ibuprofen into and through the skin. The aim of the present study therefore was to examine the influence of increasing amounts of the cosolvent ethanol on the solubility, ionization and permeation characteristics of ibuprofen through silicone and human skin.…”

Nephrotic-range Proteinuria and Interstitial Nephritis Associated with the Use of a Topical Loxoprofen Patch

“…Although topical NSAIDs are widely used due to their presumed safety, little is known regarding the safety of these drugs, especially in older patients (12). In terms of nephrotoxicity in particular, there are only a few previous reports of nephrotic syndrome and renal impairment associated with topical NSAID use (4,5).…”

In Vitro Percutaneous Permeation and Skin Accumulation of Finasteride Using Vesicular Ethosomal Carriers

“…Penetration of agents through the skin involves complex processes but it is well established that the major barrier to permeation resides within the outmost layer of skin, the stratum corneum (1). Whether it's for systemic effects or topical applications, therapeutic agents must first pass through the stratum corneum and epidermis, then enter the dermis layer and exert their further effects.…”