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8 MARCH 2011 • TransDermal pharmacokinetic parameters, the authors concluded that the MIKA formulation exhibited low systemic availability and produced effective diclofenac concentrations equivalent to or better than the oral dosage form. Other researchers conducted studies using the MIKA topical liposomal technology: a) a heparin spray used to treat superficial venous thrombosis [12, 13] and b) topical delivery of plasmid DNA to skin [14]. NexACT, MacroChem NexMed, a specialty CRO with a pipeline of products based on the NexACT ® technology, recently changed its name (September 2010) to Apricus Biosciences (www.apricusbio.com) and moved from New Jersey to California in the USA [15, 16]. Its technology is based on permeation enhancers that affect the fluidization of lipids in cellular membranes. An example of one of the compounds is dodecyl 2-(N, N-dimethylamino)-propionate. Formulators can use this technology topically, but as a recent preclinical study showed, also can deliver insulin and other drugs with larger molecular weights, such as Taxol, subcutaneously in a depot-like fashion (slow re - lease). Delivery occurs over 24 hours from a singledose formulation. Recent investigations by Michniak-Kohn’s lab at Rutgers University have shown the potential use of this technology in transbuccal delivery [17]. MacroChem, which Access Pharmaceuticals acquired (www.accesspharma.com), developed SEPA (Soft Enhancer of Percutaneous Absorption) based on dioxolane chemistry, which they have shown improves drug permeation through the skin. Diani et al published an example of the enhancement of activity, showing that 2-n-nonyl-1, 3-dioxolane augments hair-growth effects of topically applied minoxidil in the balding stump-tail-macaque model [18]. Watson Pharmaceuticals Watson Pharmaceuticals (www.watson.com) markets Gelnique ® (oxybutynin chloride) gel 10%, which is indicated for overactive bladder. It is formulated in an alcohol-based gel containing alcohol, glycerin, hydroxypropylcellulose, sodium hydroxide and purified water. The patient receives the formulation in a sachet that must be used immediately upon opening due to evaporation of the alcohol. BHR Pharma BHR Pharma (www.bhr-pharma.com) has developed a transdermal estradiol gel for the palliative treatment of vasomotor side effects in men undergoing androgen-deprivation therapy (ADT) for pros tate cancer and advanced androgen-sensitive carcinoma of the prostate. Located in Herndon, Virginia, USA, BHR Pharma is a wholly owned subsidiary of Besins Healthcare (www.besins-healthcare.com), a Belgian company, and an affiliate of Ascend Therapeutics (www.ascendtherapeutics.com), Besins’ pharmaceutical sales and marketing entity in the USA. BHR’s technology involves the Enhanced Hydroalcoholic Gel ® (EHG) that Besins pioneered and commercialized in 1975. Other products include Estrogel ® (www.estrogel.com), which is a clear and colorless topical gel containing estradiol 0.06% for treatment of menopausal symptoms and which is available in a dosing pump or tube, and Progestogel ® , a 1% progesterone hydroalcoholic gel used to treat breast pain and tenderness. Transdel Pharma Ketotransdel ® is a novel cream containing 10% ketoprofen, recommended for acute soft tissue injuries (sprains and strains). A 2010 Phase 3 study in 364 patients suggested that Ketotransdel is effective over placebo and did not produce any severe side effects. Researchers detected only minimal levels of ketoprofen in the blood of the volunteers, supporting the fact that low concentrations were absorbed systemically [19]. Transdel (ww.transdelpharma.com) focuses primarily on topical drug delivery, and the Transdel technology facilitates the dissolution of the API and enhances the passage of the drug across the barrier of the skin. Novartis, Endo Pharmaceuticals Voltaren ® is a diclofenac sodium gel that contains 10mg/g of drug with the following excipients: ammonia, carbomer homopolymer Type C, isopropyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, and water [20]. Endo Pharmaceuticals (www.endo.com) markets Novartis Consumer Health’s product for relief of pain caused by osteoarthritis of joints, such as knees and hands (www.novartis.com). Patients apply the gel using a dosing card that is supplied with the medication to ensure the correct dose of diclofenac.
Nuvo Research, Covidien, King Pharmaceuticals Pennsaid ® contains diclofenac sodium 1.5 % w/w as a topical solution with glycerin, propylene glycol, ethanol, purified water, and a skin-penetration enhancer, dimethyl sulfoxide [21, 22]. Nuvo Research (www.nuvoresearch.com), formerly Dimethaid, manufactures the product, and Covidien (www.covidien.com) markets it in the USA under license from Nuvo. In November 2009, the FDA approved Pennsaid in the USA (originally launched in Canada), where it is one of three products for osteoarthritis. The other two are Voltaren ® gel (discussed previously) and the Flector ® patch, which contains 1.3% diclofenac sodium and is a product of King Pharmaceuticals (www.kingpharm.com). Esba Laboratories Lidocaine hydrochloride topical gels are available from various manufacturers. An example is Topicaine ® from Esba Laboratories (www.esbalabs.com) [23]. This formulation contains 40 mg of lidocaine in a gel composed of water, ethanol (35% w/w), glycerin, jojoba oil, aloe vera oil, glyceryl monolaurate, benzyl alcohol, carbomer 940, and EDTA-ethylenediaminetetraacetic acid. Patients apply it topically for relief of pain, and it provides analgesia in the skin by reversibly blocking the flux of sodium ions through the neuronal membranes. AlphaRx A Canadian company, AlphaRx (www.alpharx.com), launched its Colloidal Lipid Dispersion (CLD) technology, which provides percutaneous enhancement of topically applied drugs. In addition, formulators can combine this product with polymers and adhesives for patch development and transdermal drug delivery [24]. The Flexogan BCD ® (Bioadhesive Colloidal Dispersion) series of products marketed in Canada uses this technology for arthritis and muscle and joint pain. The formulation consists of highly dispersed oil droplets encapsulating natural menthol and camphor. The droplet size is less than one micron, and the formulation is nongreasy and allows a much higher availability of the active ingredient. Embil Pharmaceuticals Embil Pharmaceuticals in Turkey (www.embil.com) has patented a novel formulation, the Sulidin ® nime- TransDermal • MARCH 2011 sulide LPS Gel [25]. The drug is indicated for osteo - arthritis, rheumatoid arthritis, periarthritis, and posttraumatic or acute musculoskeletal disorders. The LPS (Lamellar Penetration System) is based on the idea of using components of the skin structure as the delivery system. The lamellar hydrophobic structure both protects and facilitates the delivery of the API into the skin. Polytherapeutics PharmaDur ® (www.pharmadur.com) is a graft copolymer delivery system designed to address issues with polymeric delivery systems discussed above under “Formulation Considerations.” It has been commercially available over the last few years under that trade name. Kishore Shah first reported on PharmaDur and related graft copolymers for mucosal and skin applications [26]. PharmaDur polymer combines hydrophilic and hydrophobic structural moieties (Figure 1). The copolymer exhibits a combination of bioadhesive and controlled-release properties because of its unique structural characteristics [27]. When a patient applies a dermatological vehicle, such as a cream, lotion, or gel formulated with the PharmaDur polymer, the vehicle forms an imperceptible and invisible hydrogel film, a virtual patch. The PharmaDur polymer film is nontacky and nongreasy, has a very smooth feel, does not exhibit flaking or skin stretchiness, and is breathable. It is characterized by excellent bioadhesion to skin and exhibits controlled release of both hydrophobic and hydrophilic molecules. Because PharmaDur polymer is very hydro - Figure 1 PharmaDur Graft Copolymer R – alkyl radical n, m, x, y, & z – positive integers having unspecified different large values 9
Page 1 and 2: VOLUME 3 NUMBER 2 Exclusively for t
Page 3 and 4: EdiTORiAl Peggy Wright Editor pwrig
Page 5 and 6: delivery system from ViaDerm to Via
Page 7 and 8: TransDermal • MARCH 2011 Patchles
Page 9: Novavax, Abbot, Auxilium Researcher
Page 13 and 14: References 1. Quan D, Hui X, and Ma
Page 15 and 16: find their way into circulation in
Page 17 and 18: ISSUE FOCUS pharmadur ® Polytherap
Page 19 and 20: January 2012 Drug Delivery Partners

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