Aug. 30, 2012  8  US 2012/0220962 Al  TABLE 106-3  VITAMIN  A group  A1  A2  A acid  Provitarnin A  carotenoids  B group  Thiamin  Riboflavin  Niacin  Pantothenic acid  B6  Biotin  Folacin  C  D group  D2  E group  alpha› beta› garnma› delta- K group  Kl  K $_{2 }$ K3  K4-7  Vitamin Nomenclature  SYNONYM OR DESCRIPTIVE TERMS  Antixerophthalmic vitamin  Retinal  Dehydroretinol  Retinoic acid (tretinoin)  Carotene (  a  & 13 cryptoxanthin (hydroxy  13-carotene)  Formerly vitamin B complex  Vitamin B $_{1}$ , aneurin, antiberiberi vitamin  Vitamin B2, lactoflavin  Nicotinic acid and nicotinarnide,  pellagra-preventive factor  Formerly vitamin B$_{3 }$ Pyridoxine, pyridoxal, pyridoxarnine  Coenzyme R  Folic acid (pteroylmonoglutamic acid,  PGA) and folic acid polyglutamates,  tetrahydrofolic acid, formyl  tetrahydrofolic acid (formerly  citrovorum factor, folinic acid)  Antipernicious anemia vitamin,  cyanocobalarnin, hydroxocobalarnin  (formerly vitamin B$_{12}$ b),  nitritocobalamin (formerly vitamin B$_{12}$c)  L-Ascorbic acid, antiscorbutic vitamin  Antirachitic vitamin  Ergocalciferol (formerly calciferol),  activated ergosterol  Cholecalciferol, activated  7-dehydrocholesterol  Possess vitamin E activity in varying  degrees; occur as fatty acid esters  }  tocopherols & tocotrienols  Antihemorrhagic vitamin  Phylloquinone  Famoquinone  }  naturally occurring  Menadione, menaquinone  Biologically active  analogs ofmenadione  }  synthetic  [0070]  The active agent administered also may be one that  is cosmetically or "cosmeceutically" effective rather than  pharmacologically active. Such agents include, for example,  compounds that can reduce the appearance of aging or pho› todamaged skin, e.g., a-hydroxyacids, a-ketoacids, poly› meric hydroxyacids, moisturizers, collagen, marine extract,  and antioxidants such as ascorbic acid (vitamin  C), a-toco› pherol (Vitamin E), ~-tocopherol, y-tocopherol, o-toco› pherol, E-tocopherol, s$_{1}$-tocopherol, s$_{2}$-tocopherol, 17-toco› pherol,  and retinal  (vitamin A),  and/or cosmetically  acceptable salts, esters, amides, or other derivatives thereof. A  preferred tocopherol compound is a-tocopherol. Additional  cosmetic agents include those that are capable of improving  oxygen supply in skin tissue, as described, for example, in  Gross, et al, WO 94/00098 and Gross, et al, WO 94/00109,  both assigned to Lancaster Group AG. Sunscreens may also  be included.  [  0071]  The active agent may be administered, if desired, in  the form of a salt, ester, amide, prodrug, derivative, or the like,  provided the salt, ester, amide, prodrug or derivative is suit› able pharmacologically. Salts, esters, amides, prodrugs and  other derivatives of the active agents may be prepared using  standard procedures known to those skilled in the art of syn› thetic organic chemistry and described, for example, by  March’s Advanced Organic Chemistry: Reactions, Mecha› nisms and Structure,  5th Ed. (Wiley-Interscience, 2001).  [0072]  For example, acid addition salts are prepared from  the free base (e.g., an amine drug) using conventional meth› odology, by reaction with a suitable acid. Generally, the base  form of the drug is dissolved in a polarorganic solvent such as  methanol or ethanol and the acid is added thereto. The result› ing salt either precipitates or is brought out of solution by the  addition of a less polar solvent. Suitable acids for preparing  acid addition salts include both organic acids (e.g., acetic  acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid,  malic acid, malonic acid, succinic acid, maleic acid, fumaric  acid, tartaric acid, citric acid, benzoic acid, cinnamic acid,  mandelic acid, methanesulfonic acid, ethanesulfonic acid,  p-toluenesulfonic acid, salicylic acid, and the like), as well as  inorganic acids (e.g., hydrochloric acid, hydrobromic acid,  sulfuric acid, nitric acid, phosphoric acid, and the like). An  acid addition salt may be reconverted to the free base by  treatment with a suitable base. Particularly preferred acid  addition salts of the active agents herein are halide salts, such  as may be prepared using hydrochloric or hydrobromic acids.  [0073]  Preparation of basic salts of acids are prepared in a  similar manner using a pharmaceutically acceptable base  such as sodium hydroxide, potassium hydroxide, ammonium  hydroxide, calcium hydroxide, trimethylamine, or the like.  Particularly preferred basic salts herein are alkali metal salts,  e.g., the sodium salt, and copper salts.  [0074]  Preparation of esters involves functionalization of  hydroxyl and/or carboxyl groups that may be present within  the molecular structure of the drug. The esters are typically  acyl-substituted derivatives of free alcohol groups, i.e., moi› eties that are derived from carboxylic acids of the formula  RCOOH where R is alkyl, and preferably is lower alkyl.  Esters can be reconverted to the free acids, if desired, by using  conventional hydrogenolysis or hydrolysis procedures.  Amides and prodrugs may also be prepared using techniques  known to those skilled in the art or described in the pertinent  literature. For example, amides may be prepared from esters,  using suitable amine reactants, or they may be prepared from  an anhydride or an acid chloride by reaction with ammonia or  a lower alkyl amine. Prodrugs are typically prepared by cova› lent attachment of a moiety, which results in a compound that  is therapeutically inactive until modified by an individual’s  metabolic system.  [0075]  For those active agents that are chiral in nature and  can thus be in an enantiomerically pure form or in a racemic  mixture, the drug may be incorporated into the formulation  either as the racemate or in the enantiomerically pure form.  [0076]  The amount of active agent administered will  depend on a number of factors and will vary from subject to  subject and depend on the particular drug administered, the  particular disorder or condition being treated, the severity of  the symptoms, the subject’s age, weight and general condi› tion, and the judgment of the prescribing physician. Other  factors, specific to transdermal drug delivery, include the  solubility and permeability of the carrier and adhesive layer in  a drug delivery device, if one is used, and the period of time  for which such a system will be fixed to the skin or other body  surface. The minimum amount of drug is determined by the  requirement that sufficient quantities of drug must be present  in a device or composition to maintain the desired rate of  release over the given period of application. The maximum 