Navigating sticky areas in transdermal product development.

The benefits of transdermal delivery over the oral route to combat such issues of low bioavailability and limited controlled release opportunities are well known and have been previously discussed by many in the field (Prausnitz et al. (2004) [1]; Hadgraft and Lane (2006) [2]). However, significant challenges faced by developers as a product moves from the purely theoretical to commercial production have hampered full capitalization of the dosage forms vast benefits. While different technical aspects of transdermal system development have been discussed at various industry meetings and scientific workshops, uncertainties have persisted regarding the pharmaceutical industry's conventionally accepted approach for the development and manufacturing of transdermal systems. This review provides an overview of the challenges frequently faced and the industry's best practices for assuring the quality and performance of transdermal delivery systems and topical patches (collectively, TDS). The topics discussed are broadly divided into the evaluation of product quality and the evaluation of product performance; with the overall goal of the discussion to improve, advance and accelerate commercial development in the area of this complex controlled release dosage form.

[1]  M. Ashburn,et al.  A Pilot Study Assessing the Impact of Heat on the Transdermal Delivery of Testosterone , 2001, Journal of clinical pharmacology.

[2]  J. H. Kou,et al.  Effect of Receiver Fluid pH on in Vitro Skin Flux of Weakly lonizable Drugs , 1993, Pharmaceutical Research.

[3]  Robert L. Bronaugh.  Methods for in Vitro Percutaneous Absorption , 1995 .

[4]  K. Gjesdal,et al.  Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature. , 1986, American heart journal.

[5]  J. Natarajan,et al.  Pharmacokinetics of Norelgestromin and Ethinyl Estradiol Delivered by a Contraceptive Patch (Ortho Evra™/Evra™) under Conditions of Heat, Humidity, and Exercise , 2001, Journal of clinical pharmacology.

[6]  R. K. Sharma,et al.  TRANSDERMAL DRUG DELIVERY , 2010 .

[7]  R. Bodmeier,et al.  Drug release and adhesive properties of crospovidone-containing matrix patches based on polyisobutene and acrylic adhesives. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[8]  Jonathan Hadgraft,et al.  Passive transdermal drug delivery systems , 2006 .

[9]  S. Mitragotri,et al.  Enhancement of transdermal drug delivery via synergistic action of chemicals. , 2009, Biochimica et biophysica acta.

[10]  H. I. Maibach,et al.  In vivo relationship between transepidermal water loss and percutaneous penetration of some organic compounds in man: effect of anatomic site , 2004, Archives of Dermatological Research.

[11]  L. Arendt-Nielsen,et al.  Effect of local controlled heat on transdermal delivery of nicotine. , 2011, International journal of physiology, pathophysiology and pharmacology.

[12]  M. Roberts,et al.  Bovine-serum-albumin-containing receptor phase better predicts transdermal absorption parameters for lipophilic compounds. , 2003, The Journal of investigative dermatology.

[13]  R. Bronaugh,et al.  Methods for in vitro percutaneous absorption studies III: hydrophobic compounds. , 1984, Journal of pharmaceutical sciences.

[14]  Michael P. Meredith,et al.  Improving the Sensitivity of in Vitro Skin Penetration Experiments , 1994, Pharmaceutical Research.

[15]  H. Maibach,et al.  Regional variation in percutaneous penetration of 14C cortisol in man. , 1967, The Journal of investigative dermatology.

[16]  W. Steiling,et al.  Test guidelines for in vitro assessment of dermal absorption and percutaneous penetration of cosmetic ingredients. European Cosmetic, Toiletry and Perfumery Association. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[17]  R. Bronaugh,et al.  Methods for in vitro percutaneous absorption studies IV: The flow-through diffusion cell. , 1985, Journal of pharmaceutical sciences.

[18]  A. Hussain,et al.  Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  T. Franz.  Percutaneous absorption on the relevance of in vitro data. , 1975, The Journal of investigative dermatology.

[20]  H. Maibach,et al.  Regional variation in percutaneous absorption in man: measurement by the stripping method , 2004, Archives of Dermatological Research.

[21]  Priyanka Ghosh,et al.  Challenges and opportunities in dermal/transdermal delivery. , 2010, Therapeutic delivery.

[22]  H. Maibach,et al.  Variations in percutaneous absorption of testosterone in the rhesus monkey due to anatomic site of application and frequency of application , 2004, Archives of Dermatological Research.

[23]  S. Mitragotri,et al.  Current status and future potential of transdermal drug delivery , 2004, Nature Reviews Drug Discovery.

[24]  M. Ashburn,et al.  Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. , 2000, Pain medicine.

[25]  J. Howell,et al.  Results from four pharmacokinetic studies of the granisetron transdermal system , 2013 .

[26]  J. Natarajan,et al.  Pharmacokinetic overview of Ortho Evra/Evra. , 2002, Fertility and sterility.

[27]  R. Guy,et al.  FDA and AAPS Report of the Workshop on Principles and Practices of In Vitro Percutaneous Penetration Studies: Relevance to Bioavailability and Bioequivalence , 1987, Pharmaceutical Research.

[28]  V. Meidan,et al.  Validation of a Static Franz Diffusion Cell System for In Vitro Permeation Studies , 2010, AAPS PharmSciTech.

[29]  R. Guy,et al.  Methods for Assessing Percutaneous Absorption , 1996 .

[30]  K. Brain,et al.  Methods for Studying Percutaneous Absorption , 2002 .

[31]  Mario A. González,et al.  Passive Transdermal Systems Whitepaper Incorporating Current Chemistry, Manufacturing and Controls (CMC) Development Principles , 2012, AAPS PharmSciTech.

[32]  M. Ashburn,et al.  The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat. , 2003, The journal of pain : official journal of the American Pain Society.

[33]  H I Maibach,et al.  Regional variation in percutaneous penetration in man. Pesticides. , 1971, Archives of environmental health.

[34]  Buket Aksu,et al.  Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT). , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[35]  Brian W. Barry,et al.  Effects of penetration enhancer treatment on the statistical distribution of human skin permeabilities , 1995 .

[36]  J. Natarajan,et al.  Randomized 5‐Treatment Crossover Study to Assess the Effects of External Heat on Serum Fentanyl Concentrations During Treatment With Transdermal Fentanyl Systems , 2012, Journal of clinical pharmacology.