Dermal preparations preparation

SAFETY PROFILE Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic and tumorigenic data. Mutation data reported. Used in pharmaceutical and dermal preparations as an emulsifying agent. When heated to decomposition it emits acrid smoke and irritating fumes. 

Aluminum tubes are often used as the immediate package for dermal preparations. One important point to remember is that after the application of creams, ointments, or gels to the skin, all of the photo protection provided by the packaging is lost and photodegradation can occur. Topically applied drug substances with proven photoinstability, e.g., corticosteroids (36), retinoic acid (37), dithranol (38), and anti-mycotics (natamycine and nystatine) (39) fall into this category. 

Liposomes are widely used in dermal preparations (dermatics) for various reasons. Cyclodextrins play a role in the solubilization of poorly soluble drugs. Hence, their use in dermatics is rarely restricted. 

Photoexposure of unprotected skin after the administration of dermal preparations containing corticosteroids or antimycotics may cause photodegradation of the... 

Rectal and vaginal dosage forms aimed to obtain a local effect are, from a biopharmaceutical viewpoint, comparable with dermal preparations. However it should be known that after rectal and vaginal application a greater part of the active substance may reach the general circulation than after cutaneous application. This may result in significant blood levels and unwanted systemic effects. 

High lipid solubility and low molecular weight enhance the absorption through the vaginal mucosa. As for dermal preparations absorption occurs primarily by passive diffusion. Therefore active substances intended for a local effect should have a limited lipophilicity, in order to prevent systemic action [59]. 

Sterile cutaneous preparations undergo sterilisation in the final container if possible. Many active substances, base preparations and package materials for cutaneous preparations however are not resistant to the common sterilisation methods, see also Sect. 30.8. If sterilisation in the final container is not possible, cutaneous dermal preparations should be prepared aseptically and packaged in sterile packaging materials, see Chaps. 30 and 31. On the label of sterile cutaneous preparations the word sterile has to be mentioned. After opening, these preparations can only be stored for 24 h. 

In dermal preparations ion-pair formation between icuiic surfactants and an active substance may reduce the local availability of the active substance. An example is the interaction between the anion laurylsulfate (from the surfactant sodium laurylsulfate) and the cationic neomycine or tetracycline in creams. 

The pH of the vehicle in relation to the skin pH (around 5.5) is very important. Many active substances, also in dermal preparations, are weak acids or bases. The pH partition theory (see 16.1.9) plays a role here as well and affects the effective partition of the active substance between the vehicle and the skin. 

Physiological factors also determine the effectiveness of dermal preparations. The thickness of the skin varies across the body. The penetration rate is higher when applied on thin skin (e.g. behind the ear, on the eyelid or scrotum) than when applied on thick skin (e.g., palm of the hand, sole of the foot). Comparing the skin of babies and adults, the ratio between body surface (skin) and body volume is larger for babies. In addition, skin absorption in term and in preterm new-boms is increased because their stratum comeum is thinner and the epidermis of children is better perfused and hydrated compared to adults. As a result, the toxicity of active substances applied on a baby s skin can be much higher than on an adult s skin. 

As an example, the photodegradation products of chloramphenicol (nitroso-compounds and paranitro-benzaldehyde) are considered carcinogenic. These products will be formed in vitro and in vivo and can reach the bone marrow in rats [37]. Chronic use of chloramphenicol has been coimected with bone marrow depression, not caused by chloramphenicol itself. Apart from the question if this risk is estimated well [38], it can be avoided completely if the patient covers his skin if a dermal preparation has been applied and only use chloramphenicol as eye ointment 1 % at night. See also Sect. 10.5. 

Dermal preparations solutions, suspensions and emulsions for cutaneous use, shampoos... 

Semisolid (dermal) preparations that are too viscous or too physically unstable to be dispensed in a tube... 

Triamcinolone acetonide in dermal preparations is processed as a trituration with rice starch (1 10). Here, the particles of triamcinolone acetonide are reduced in size firstly by dissolving the substance in a volatile solvent, after which this solution is rubbed until dry with rice starch. The resulting particles of triamcinolone acetonide of about 5 pm are in this way mixed with and held apart by the starch particles. By pulverising triamcinolone acetonide as such in a mortar such fineness of particles is not achieved. Moreover, agglomerates will be created. Also rubbing the solution until dry without rice starch does not yield a good result. Not only agglomerates will be recreated, but part of the triamcinolone acetonide will crystallise in a coarser form. 

Mixing of solids takes place in the pharmacy in the preparation of capsules, single-dose powders and multidose powders. But also in the preparation of suppositories and dermal preparations solids may first be mixed together before they are combined with the base. A common reason for this is that mixing solids may give an opportunity to ... 

Also, an increased incidence of cell-mediated and humoral immunity to various collagens has been found in systemic connective tissue disease such as rheumatoid arthritis, juvenile rheumatoid arthritis, and progressive systemic sclerosis (scleroderma). Patients with these diseases may thus have an increased susceptibility to hypersensitivity responses and/or accelerated clearance of their implants w hen injected with bovine dermal collagen preparations. Therefore, caution should be used when treating tliese patients including consideration for multiple skin lesions. 

Due to their strongly anisometric particle shape, triglyceride SLN tend to self-aggregate and build-up stacked lamellae at higher concentrations. The formation of such stacked lamellae was found to be reversible upon dilution and did not lead to an accelerated physical instability of the dispersions. The anisometric particle shape also determines the flow properties of SLN dispersions and high lipid contents (up to 40%) led to the formation of an elastic gel with viscoelastic properties comparable to standard dermal preparations. ... 

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