Topically applied remedies provide controlled release of herbs directly into the bloodstream through the skin. They provide a number of advantages over conventional methods of herbal administration, including:

• Enhanced efficacy.
• Increased safety.
• Greater convenience
• By delivering a steady flow of herbs into the bloodstream over an extended period of time, transdermal systems can avoid the "peak and valley" effect of a oral therapy and can enable more controlled, effective treatment.
• By avoiding first pass metabolism through the gastrointestinal tract and the liver, the therapeutically equivalent dosage for the transdermal delivery of certain compounds can be significantly less than the corresponding oral dosage, potentially reducing dosage related side-effects.
• Easy to terminate dosing if adverse reaction occurs.

Rosa+ - Rosacea Treatment Delivery System:

• The concentration and solubility of the active ingredients: high concentration or solubility penetrate better (high concentration gradient)
• Vehicle viscosity: viscosity reduces diffusion coefficient.
• Vehicle composition: non-aqueous solvents increase penetration.
• Penetration enhancers: disrupt skin surface causing faster penetration.
• Area for absorption: increased area causes increased absorption.

Physiological conditions in skin:

• Dead cells and lipid accumulation in the stratum corneum decreases initial transport.
• Sebum-pH, amount and composition alter passage.
• Hydration of the skin ( differ according to the person's age and skin location): increased hydration usually increases penetration rate.
• Thickness of the skin: Thin skin causes increased penetration rate e.g. the skin behind the ear is very thin while that of palm of hand is very thick.
• Injury- open cuts and grazes increase penetration rate.
• Temperature: Theoretically, a positive relation is expected between skin temperature and the percutaneous penetration of topically applied substances. Studies showed that temperature effect with the highest penetration is at 38.2 degrees C (4).

Skin Permeation Enhancers
One literature review found more than 275 chemical compounds cited as skin penetration enhancers (5).
Most of those compounds were generally recognized as safe (GRAS) ingredients that would often be considered inert by a formulator. Complete texts concerning pharmaceutical skin penetration enhancement are available and they provide excellent descriptions and critical reviews of this subject (6,7,8).
Although there are many strategies to enhance skin permeation, some of them include the use of chemical skin penetration enhancers. We use natural additives that:

• Alter the solubility of the active ingredient in the formulation (including supersaturation), to increase its delivery through the skin
• Optimize the ionization state of the active ingredients in the topical remedies (using buffered gel with the proper pH).
• Enhance the skin permeation (adding natural skin permeation enhancers).

Topical products often contain many components that are considered inert excipients with respect to the pharmacology:

• Solvents and cosolvents are used to alter drug solubility or ease of processing.
• Emulsifiers and gelling agents provide the consistency and properties expected of creams, lotions, and gels.
• Antioxidants and preservatives are provided to extend shelf life or ensure quality.
• Skin permeation enhancers are added to the topical treatments to increase skin permeability by reversibly altering the physiochemical nature of the stratum corneum to reduce its diffusional resistance (8).

We use the natural skin enhancers which include:

• Iontophoresis: uses electrical potential to carry drug through the skin, by using active ingredients in buffered gel.
• Linoleic acid and alpha-linolenic: It has been found that polyunsaturated fatty acids PUFA--Linoleic (LA), alpha-linolenic (ALA) and arachidonic acids-enhance skin permeation stronger than monounsaturated fatty acids. The enhancement effects of fatty acids on penetration through the stratum corneum are structure-dependent, associated with the existence of a balance between the permeability of pure fatty acids across stratum corneum and the interaction of the acids to skin lipids (9).
• Oleic acid: Oleic acid has been studied as a skin penetration enhancer for topically applied medications, primarily via its action mainly on the stratum corneum lipid structure. It has been found to increase the epidermal permeability through a mechanism involving the stratum corneum lipid membrane. It is incorporated into skin lipid, disrupt molecular packing and alter the level of hydration and allow drug penetrates faster (10).
• Cod-liver-oil The enhancing effect of the marine products could generally be associated with their content of free unsaturated fatty acids (11).
• Menthol derivatives as potential skin penetration enhancers Studies showed that the permeation enhancing effect of l-menthol is significantly high with short lag time (12). The promoting activity of the ethyl ether derivative of Menthol is the greatest of all menthol derivatives. Studies showed that it is the most promising compound which has the greatest action and relatively low skin irritancy (13,14). A study has been made to elucidate the mechanism of skin permeation enhancement and it was concluded that the increase in skin flux, to eight times the base line, could be attributed to the effect of menthol on the skin barrier properties (15). The mechanism of permeation enhancement of menthol has been studied by some other investigators and they concluded that it could involve its distribution preferentially into the intercellular spaces of stratum corneum and the possible reversible disruption of the intercellular lipid domain. They suggested the use of menthol as effective penetration enhancer (16).
• Squalene: Squalene was found to be a very effective skin permeation enhancer. 12% of the human sebum is composed of Squalene to which is attributed the natural moisturizing effect of the sebum. Studies also showed the skin soothing effect of Squalene (17).
• Glycerol derivatives: Studies concluded that glycerol monoethers derived from linear saturated fatty alcohols are very effective permeation enhancers (18).
• Herbal ingredients: have the ability to penetrate the skin fast. In vivo skin penetration studies of the Chamomile flavones apigenin, luteolin and apigenin 7-O-beta-glucoside were carried out with nine healthy, female volunteers. During seven hours the decline of flavonoid concentration in a saturated aqueous alcoholic solution filled in application chambers were repeatedly measured by spectrophotometry at fixed time periods. It was concluded, that the flavonoids are not only adsorbed at the skin surface, but penetrate into deeper skin layers. This is important for their topical use as antiphlogistic agents (19).
Another study has been done to investigate the permeability of natural herbal compounds of different range of lipophilicity through hairless mouse skin and the effect of certain herbal extract called Senkyu(Ligustici Chuanxiong Rhizome )ether extract (SEE) as permeability enhancer. It has been found that (Senkyu) ether extract (SEE) enhanced the permeability of the herbal ingredient that have moderate permeability rate. The effect of SEE in vivo was similar to that obtained in the in vitro experiment. It was concluded that the natural compounds having high lipophilicity sufficiently permeated into the hairless mouse skin owing to their accumulative property, and the Senkyu ether extract enhanced the permeability of the moderately lipophilic compounds into the skin (20).

By using combination of buffered gel and skin permeation enhancer in addition to the easily permeable herbal ingredients, extracted by natural solvents, further increases the flux through the epidermis. It has been concluded after several studies that Iontophoresis in combination with enhancers (e.g. linolenic acid ) transformed the highly compact cells of the Stratum corneum into a looser network of filaments, disrupted the keratin pattern, and resulted in swelling of Stratum corneum cell layers of human epidermis, thus increases the flux of medication through human epidermis (21).
Our scientists are and will always be appreciating the trust of their customers all over the world. They will always make use of their unique creative feature in developing the best of the topical herbal remedies to protect their customers from the side effect of the long term use of pharmacological drugs.

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