Dermal preparations application

The generally low lipid content and the poor viscosity of lipid nanodispersions make these preparations, as they are, less suitable for dermal drug application. The handling of the preparation by the patient is improved by SLN incorporation into ointments, creams, and gels. Alternatively, ready-to-use preparations may be obtained by one-step production, increasing the lipid phase to at least 30%. However, increasing the lipid frequently results in an unwanted increase in particle size. Surprisingly, it has been found that very concentrated (30 to 40%) semisolid cetyl palmitate formulations preserve the colloidal particle size [10]. 

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. 

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. 

Obviously, if you wish to treat a skin condition or infection, a preparation that can be applied topically would be the preferred option. Similarly, inhalation would be the first choice if trying to treat a pulmonary or bronchial condition, such as asthma. Dermal application would also be the first choice for localized tissue treatments (e.g. muscle injury), provided that the drug can be absorbed through the skin. However, in most other situations it is necessary for drugs to enter the bloodstream in order for them to be transported to their site of action. This is most commonly achieved by ingestion, or by intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) injection when the oral route is not suitable. 

The death of a 10-year-old girl following dermal exposure to acrylonitrile was reported by Lorz (1950). An acrylonitrile preparation had been applied to the scalp of the child as a treatment for head lice. The child experienced nausea, headache and dizziness. Death occurred 4 hours after application. The concentration was not specified in this case report. 

There are few studies that specifically describe the effects of heptachlor or heptachlor epoxide in humans following exposure via the oral, inhalation, or dermal routes. There are data on the health effects of chlordane from occupational studies of pesticide applicators and manufacturers, and from studies of people who consumed food contaminated with chlordane and heptachlor. Chlordane is a pesticide that is structurally similar to heptachlor, and technical-grade preparations may contain... 

Polybrominated Diphenyl Ethers. No information was located regarding dermal absorption of PBDEs in humans. The only information regarding dermal absorption in animals is that from a study of absorption in an in vitro preparation (Hughes et al. 2001). In that study, " C-dccaBDE dissolved in tetrahydrofuran was applied to dorsal skin (three dose levels) excised from adult hairless female mice and fractions of receptor fluid were collected over a 24-hour period. Transfer of radioactivity to the receptor fluid was minimal, only 0.07 to 0.34% of the applied radioactivity. Two to 20% of the radioactivity was found in the skin, and the lowest dose applied had the highest percentage of the dose in the skin. Washing the skin with solvent 24 hours after application removed 77-92% of the applied dose. In this study, decaDBE did not easily penetrate the skin, but inferences to dermal absorption in humans based on these limited results may not be appropriate. 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. For example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m3, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD50,4000 mg/kg, whereas the acute oral toxicity is LD5Q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have FDA approval for reuse food applications. 

These reagents have a number of drawbacks. First of all, they are toxic especially via contact with skin. The LD50 (dermal, rat) of DCC is 71 mg kg. This should always be considered if the reaction is used for the preparation of materials for biological applications. Moreover, the N.N -dialkylurea formed during the reaction is hard to remove from the polymer except for preparation in DMF and DMSO, where it can be filtered off. In case of esterification of polysaccharides in DMSO in the presence of these reagents, oxidation of hydroxyl functions may occur due to a Moffatt type reaction (Fig. 25, [188]). The oxidation products formed can be detected with the aid of 2,4-dinitrophenylhydrazine, e.g. in case of the conversion of dextran with DCC in DMSO [189],... 

Liquid preparations intended for dermal application contain the largest variety of cosolvents. They most commonly include ethanol, isopropanol, propylene glycol, glycerin, and PEG 400. Irritation and sensitization are important considerations in choosing a cosolvent for dermal use. In addition, it may be necessary to... 

In the case of dermal exposure, the contaminated area must be washed with plenty of water and soap. Topical application of vitamin E preparations may help to reduce the severity of skin reactions. The affected eye must be irrigated with lukewarm water for at least 10 min. The contaminated clothing is removed and the airway cleared. In the case of ingestion, gastric lavage is avoided as solvents present in cyfluthrin formulations may increase the risk of aspiration pneumonia. Atropine (adults and children >12 years 0.6-1.2mgkg children <12 years 0.02 mg kg by IV infusion) may be useful to... 

Exposed skin should be washed promptly with soap and water. Dermal application of vitamin E oil preparations may be used for both prophylaxis and treatment of paresthesia. Eor contact with eyes, flush immediately and for an extended period with generous amounts of clean water or saline. Gastric lavage is indicated if patient has ingested a large amount of pyrethroid and can be treated soon after exposure. For ingestion of smaller amounts or if treatment has been delayed, activated charcoal and catharsis are indicated. Seizures can be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenytoin or phenobarbital may be helpful for recurrent seizures. No specific antidotes for pyre-throid-induced neurotoxic effects have been approved for use in humans. Spontaneous recovery usually occurs with mild or moderate intoxication. 

Exposed skin should be washed promptly with soap and water. Dermal application of vitamin E oil preparations may be used for both prophylaxis and treatment of paresthesia. For contact with eyes, flush immediately and for an extended period with generous amounts of clean water or saline. Gastric lavage is indicated if patient has ingested a large amount of pyrethroids and can be treated soon after exposure. 

The depth of skin necrosis is directly proportional to the concentration of the TCA. Necrosis should not be the only endpoint of a TCA peel - stimulation also plays an important role. Repeated application of less concentrated TCA helps rebuild the papillary dermis directly and/or indirectly as a result of the repeated dermal irritation of the peel-induced inflammation. It is possible to reach the dermis using a low-concentration solution apphed to an epidermis that has been made temporarily more permeable by a prior peel or robust preparation. 

After leaving the solution to rest for 24 hours and filtering it, UV exposure was what made it effective Solutions not exposed to UV did not appear to work. The skin was also prepared by UV exposure, and the solution was applied five times, leaving each coat to dry before the next application. Urkov then applied an occlusive mask. This mask allowed the superficial layers to hyperhydrate by blocking transepi-dermal water loss (TEWL). The hyperhydration dissolved the salicylic acid that would have precipitated on the skin without occlusion and could not have penetrated, as only the acids in solution can readily penetrate the skin barrier. He then applied zinc stearate powder (which is antiseptic and anti-inflammatory). The erythema subsided in 5-6 days and exfoliation was superficial. The solution can be kept in the fridge for 10 days. 

Recent stndies on hnman volnnteers demonstrated that CyDs have a significant safety margin in dermal application. Optimized release of the drng from the topical preparation containing its CyD complex may be obtained by... 

In New Zealand white rabbits, patches soaked with 0.5 mL of undiluted 2-butoxyethanol acetate were applied to one site of the prepared skin surface (Jacobs et al. 1989). The untreated skin was used as a control. Erythema scores were obtained 1, 24, 48, and 72 hours after application of the undiluted substance for 4 hours. The erythema scores of exposure to 100% 2-butoxyethanol acetate for 4 hours in rabbits showed a ranking of 2, which is the minimal mean erythema needed to classify substances as skin irritants. New Zealand rabbits exposed dermally to unspecified doses of 2-butoxyethanol acetate for 24 hours exhibited dermal effects (Truhaut et al. 1979). When 2-butoxyethanol acetate was tested for primary irritation of the skin, four of six rabbits showed slight erythema (grade 1) at 24 hours. Dermal irritation from exposure to 2-butoxyethanol acetate has been studied in rabbits using both the Draize protocol (24-hour occluded exposure) and the European Economic Communities protocol (4-hour occluded exposure) (Zissu 1995). For both protocols, 0.5 mL of undiluted 2-butoxyethanol acetate was placed on the skin. 2-Butoxyethanol acetate was considered a moderate irritant by the Draize protocol and non-irritating by the European Economic Communities protocol. 

It is also apparent that little effort is made to optimize the vehicle for topically administered sensitizers (e.g., dermal, oral cavity). For such applications, one is frequently presented to simple aqueous solutions of ethanol or DMSO. Topical preparations thereby offer a challenge to the formulation expert. Application to the oral cavity and larynx would benefit from bioadhesive formulations to increase the contact time between sensitizer and tissue. A well-designed vehicle could allow topical administration of sensitizers to tumors located close to the skin surface and thus offer an alternative to the present systemic administration. 

In the chemical industry (on the mega- as well as the micro-scale) fine emulsions have many useful applications in, e.g., extraction processes or phase transfer catalysis. Additionally, they are of interest for the pharmaceutical and cosmetic industry for the preparation of creams and ointments. Micromixers based on the principle of multilamination have been found to be particularly suitable for the generation of emulsions with narrow size distributions [33]. Haverkamp et al. showed the use of micromixers for the production of fine emulsions with well-defined droplet diameters for dermal applications [38]. Bayer et al. [39] reported on a study of silicon oil and water emulsion in micromixers and compared the results with those obtained in a stirred tank. They found similar droplet size distributions for both systems. However, the specific energy required to achieve a certain Sauter mean diameter was 3-1 Ox larger for the macrotool at diameters exceeding 100 pm. In addition, the micromixer was able to produce distributions with a mean as low as 3 pm, whereas the turbine stirrer ended up with around 30 pm. Based on energy considerations, the intensification factor for the microstirrer appears to be 3-10. 

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