title: High throughput screening of transdermal formulations.
abstract: OBJECTIVE
  Applications of transdermal drug delivery are limited by low skin permeability. Many chemicals have been used to enhance skin permeability, however, only a handful are actually used in practice. Combinations of chemicals are likely to be more efficient in enhancing skin permeability compared to individual enhancers. However, identification of efficient enhancer combinations is quite challenging because many chemical enhancers interact with each other and with the skin in a complex manner. In the absence of a fundamental knowledge of such interactions, we need to rely on rapid methods to screen various enhancer combinations for their effectiveness. In this paper, we report a novel high throughput (HTP) method that is at least 50-fold more efficient in terms of skin utilization and up to 30-fold more efficient in terms of holdup times than the current methods for formulation screening (Franz diffusion cells).
  
  
  METHODS
  A high throughput method was developed based on skin conductivity and mannitol penetration into the skin. This method was used to perform at least 100 simultaneous tests per day. Detailed studies were performed using two model enhancers, sodium lauryl sulfate (SLS) and dodecyl pyridinium chloride (DPC). The predictions of the high throughput method were validated using Franz diffusion cells.
  
  
  RESULTS
  High throughput screening revealed that mixtures of SLS and DPC are significantly more effective in enhancing transdermal transport compared to each of them alone. Maximum efficiency was observed with near-equimolar mixtures of SLS: DPC. The predictions of the HTP method compared well against those made using Franz diffusion cells. Specifically, the effect of surfactant mixtures on skin conductivity and mannitol permeability measured using Franz cells also showed a maximum at near-equimolar mixtures of SLS: DPC.
  
  
  CONCLUSIONS
  The novel HTP method allows rapid screening of enhancer formulations for transdermal applications. This method can be used to discover new and effective enhancer mixtures. At the same time, these data may also broaden our understanding of the effect of enhancers on skin permeability.
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara 93106, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Karande
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000279:Administration, Cutaneous; D000465:Algorithms; D000818:Animals; D001692:Biological Transport; D004058:Diffusion; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008353:Mannitol / Q000493:pharmacokinetics; D010539:Permeability; D011726:Pyridinium Compounds / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012879:Skin Physiological Phenomena; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013552:Swine; D013678:Technology, Pharmaceutical
chemical_list: D000277:Adjuvants, Pharmaceutic; D011726:Pyridinium Compounds; C001524:Laurosept; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol