RESUMEN
The purpose of this review is to summarize essential biological, pharmaceutical and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin, routes of drug absorption and their limitations is then provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory, microbial infections, skin cancers and genetic skin diseases. The complexity of topical product development through to large scale manufacture along with recommended risk mitigation approaches is then highlighted. As such topical treatments are applied externally patient preferences along with the challenges they invoke are then described and finally the future of this field of drug delivery is discussed with the emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. Significance Statement This review of the key aspects the skin, its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient populations preferences and limitations and the future with regards to new skin diseases and topical medicine approaches.
RESUMEN
Background: Topical corticosteroids (TCS) and emollients are developed independently by the pharmaceutical industry but are often used together in practice. There is potential for the TCS and emollient formulations to interact on the skin surface affecting TCS absorption into the skin. Clinical guidelines acknowledge this issue but lack an evidence base and differ in their recommendations. There is a current clinical need to establish whether the application protocol employed for TCS and emollient products can impact delivery of TCS to the skin. Objectives: To investigate whether the sequence of application of a TCS and emollient and the time between their application can affect TCS skin absorption. Methods: The delivery of mometasone furoate (MF) to ex vivo human skin was evaluated following the application of Elocon cream either 5 or 30 min, before and after three different emollients. Mechanistic explanation of the changes in drug absorption was provided by modelling the skin permeation data and Raman microscopy of mixed Elocon cream and emollient formulations. Results: A circa fivefold difference in MF absorption was observed depending on the emollient and application protocol. Applying Elocon cream at short intervals in relation to Hydromol intensive significantly increased MF absorption regardless of the application protocol. In contrast, applying Elocon cream after Diprobase cream or ointment significantly reduced MF absorption relative to Elocon cream alone or when Elocon cream was applied before these emollients. The changes in drug absorption observed were attributed to the presence of emollients altering Elocon cream formulation performance through different mechanisms, including introduction of penetration enhancing excipients and inducing drug crystallization in the mixed TCS emollient layer on the skin surface. Conclusions: Emollients can affect MF absorption in different ways depending on the emollient and sequence of administration. Using a 30 min gap between product applications may not be sufficient to mitigate emollient effects on TCS absorption.