Foam: A Unique Delivery Vehicle for Topically Applied Formulations

Transcription

1 : A Unique Delivery Vehicle for Topically Applied Formulations Dov Tamarkin, PhD ix Ltd. Key Words:, Emulsion, Lipophilic Emulsion, Nanoemulsion, Aqueous, Hydroethanolic, Potent-Solvent, Suspension, Ointment, Ointment, Oil, Saccharide Introduction The paramount objective of pharmaceutical and skin care product development is to create effective products based on state-of-the-art active ingredients with improved patient compliance and usability. The used to deliver topical active ingredients can considerably influence the performance of the active ingredients. The can have a direct effect on the condition of the skin as a barrier, as it can enhance or retard the delivery of the active agent to the target site of action. In addition it can affect the skin s physical appearance and sensory properties, attributes that can influence patient compliance. While semi-solid compositions, such as creams, lotions, gels, and ointments are commonly used by consumers, new forms are desirable, in order to achieve improved control of the application, increased skin absorption, and to maintain or bestow the skin promised beneficial properties. is becoming a prominent delivery system for topical active agents in skin treatment. This platform provides an innovative, easy to apply, modern alternative to creams and ointments. A significant advantage of the foam is that it spreads easily on large skin areas, does not leave a greasy or oily film on the skin after application and does not impart a greasy feeling upon and after application. The use of foam in dermatology was first reported in 1977 by Woodward and Berry who studied the therapeutic benefit of Betamethasone benzoate, in hydroalcoholic quick-break foam in comparison with a corresponding semisolid dosage form. 1 The activity of the foam, as determined by a vasoconstriction 233

2 : A Unique Delivery Vehicle for Topically Applied Formulations test, was similar to the corresponding ointment and better than a cream. In 1995, Deaffontio et al. investigated the anti-inflammatory and analgesic profile of a topical foam of ketoprofen lysine salt, which exhibited anti-inflammatory and analgesic effectiveness and favorable usability properties. 2,3 A comprehensive review on foam drug delivery in dermatology was written by Carryn et al. in Tamarkin et al. published a broad review, titled Emollient foam in topical drug delivery, in 2006; 5 and an additional review, titled : The Future of Effective Cosmeceuticals, was published in Cosmetics & Toiletries magazine in More recently, in 2010, Steckel et al. wrote a review on foam technology, titled s for pharmaceutical and cosmetic application. 7 Overview of the Market: Current Technologies Currently, only a few dermatological foam products are commercially available. Epi (Alaven Pharmaceutical LLC), which contains hydrocortisone acetate 1% and pramoxine hydrochloride 1%, is based on an aqueous foam. It is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. 8 Olux and Luxiq (Stiefel, a Glaxo SmithKline (GSK) company), which contain 0.05% clobetasol propionate and 0.12% betamethasone valerate, respectively, are both thermolabile (temperature-sensitive) steroid hydroethanolic foams (containing about 60% ethanol). 9,10 Evoclin (Stiefel) is another hydroethanolic foam, comprising 1% clindamycin, which is indicated for acne Stiefel, a GSK company further markets four emollient foams, namely Olux-E (0.05% clobetasol propionate) and Verdeso (0.05% desonide) for corticosteroid-responsive dermatoses, Sorilux (0.005% calcipotriene) for psoriasis, and Fabior (0.1% tazarotene) foam for acne Scytera (Promius Pharma, developed by ix), is a non-prescription foam containing 2% coal tar for the treatment of psoriasis, which is effective and highly convenient. 15 While coal tar preparations in general are associated with poor patient compliance as they cause skin irritation, staining to clothes, hair and skin, and are malodorous, 16 Scytera s color intensity is off-white, and thus does not cause staining; moreover, its fragrance is pleasant. Stiefel and ix are both market leaders in foam technology and are engaged in the development of innovative foams in collaboration with several pharmaceutical companies. This chapter will describe what foam is, survey the various types of foam available today commercially along with those presently under development, and exemplify their uses in skin therapy. It will further account for the physiochemical properties of foam products and explain how to evaluate them. Please note that the term drug is used extensively throughout this chapter, as the source of much discussion is based on such research; however, the principles of foam delivery systems apply equally well to personal care product types and so for the purposes of this writing, the terms, as regards their methods of application, may be considered synonymous. 234

3 The Rosetta Stone of To date, all foams are collectively designated as Medicated s by the European Pharmacopoeia, and the U.S. Pharmacopoeia simply lists Aerosol as a sub-part of its Aerosol section. 17 Most foams used in pharmacological and cosmetic applications are aerosol foams, which comprise a semi-solid, packaged in an aerosol can and pressurized by a propellant. It is imperative to understand that while a foam preparation exhibits distinct characteristics that differentiate it from other generically used s, not all foams are similar and they can be tailored to fulfill product properties requirements. While in the past there were just a few types of medicated foam, i.e., aqueous foams, hydroethanolic foams and emulsion-based emollient foams, today there are several new classes of foam s under development, mainly by ix, which are distinct in their composition and functionality from each other. Examples of new classes of foams are petrolatum-based foam, which is the foam version of an ointment; hydrophilic solvents (such as PEG and propylene glycol) based foam, which is the foam version of a hydrophilic ointment; and oil-based foam, which corresponds to oil solutions or suspensions. s that are based on potent solvents, such as dimethyl isosorbide and dimethyl sulfoxide (DMSO) contribute to high solubility and enhanced transdermal drug delivery of active agents. Also under development are hydroethanolic foams (containing high levels of ethanol) which are suitable mostly for scalp treatment because they collapse easily and do not impart greasiness to the scalp and hair. s can be also used to further stabilize suspensions and there are foams that contain high levels of saccharides and honey for wound and burn therapy. These versatile foam classes have been used to develop a large number of foam products, containing a variety of active ingredients, such as antibiotic agents, antifungals, antiviral agents, immunomodulators, corticosteroids, steroid hormones, anti-acne agents, anti-psoriasis agents, vitamins A, B, C, D and E, a-hydroxy and b-hydroxy acids, and skin barrier-building agents for the treatment dry skin conditions. It is important for the scientist to understand the differences between the above classes of foam s, and be able to select the right type of for a given clinical condition. The current review presents the Rosetta Stone of foam. It introduces the various types of foam technology platforms and suggests a functional transformation of their respective traditional topical dosage forms. Table 1 lays out a series of foam classes, which correspond to their current topical dosage forms, with a summary of the main features and attributes of each class of foam; and the following sections will provide further features of each of these classes. 235

4 : A Unique Delivery Vehicle for Topically Applied Formulations Table 1. Classification of foam technology platforms, corresponding to traditional topical dosage form designations Class characteristics Traditional topical dosage form designation (USP and EP, combined) Attributes Water-containing s Emulsion Lipophilic Emulsion Nanoemulsion Oil-in-water emulsion Water-in-oil emulsion Oil-in-water nanoemulsion Emulsion, Cream, cream Emulsion, Cream, Lipophilic cream Can carry lipophilic and hydrophilic and retain their stability Favorable usability, enhance compliance Improved solubility and skin delivery of active agents Aqueous ingredients = water, gelling agents and surfactants Gel Non-greasy Hydroethanolic ingredients = ethanol and water Solution, Tincture thereby increasing their bioavailability Suitable for oily skin areas Potent-Solvent Water and strong solvents Gel, solution thereby increasing their bioavailability Induces skin penetration Suitable for transdermal drug delivery Suspension Suspended drug in a foam Topical suspension Can carry suspended and retain their stability Favorable usability 236

5 Class characteristics Traditional topical dosage form designation (USP and EP, combined) Attributes Water-free s Ointment petrolatum main ingredient (up to 90%) Ointment, White ointment, Hydrophobic ointment Occlusive, builds up skin barrier Prolongs drug skin residence Greaseless ointment base Ointment PEG, propylene glycol, glycerin or other hydrophilic solvents main ingredients Polyethylene glycol ointment, ointment Humectant, provides skin moisturization thus rendering them more bioavailable Builds up skin barrier Oil liquid oil main ingredient Oil solution or suspension Nourishes and lubricates the skin Prolongs drug skin residence Saccharide Monosaccharides, disaccharides, honey main ingredients (up to 90%) Hygroscopic, absorbs exudates Antibacterial Useful for wounds and burns treatment Water-containing s The early generation of medicated foams included the aqueous foam, the hydroethanolic foam and the newer platform of emulsion-based foam, also termed 237