used provided the formulation remains shakable. In other  certain limited embodiments the upper limit for foamable  formulations may be determined by flowability such that any  effective amount can be used provided the formulation is  sufficiently flowable to be able to flow through an actuator  valve and be released and still expand to form a good quality  foam. This may be due without being bound by any theory to  one or more of a number of factors such as the viscosity, the  softness, the lack of crystals, the pseudoplastic or semi  pseudo plastic nature of the composition and the dissolution  of the propellant into the composition.  In certain embodiments the amount of surfactant or com› bination of surfactants is between about 0.05% to about 20%;  between about 0.05% to about 15%. or between about 0.05%  to about 10%. In a preferred embodiment the concentration of  surface active agent is between about 0.2% and about 8%. In  a more preferred embodiments the concentration of surface  active agent is between about 1 % and about 6% or between  about 1 % and about 4%.  In some embodiments, it is desirable that the surface active  agent does not contain a polyoxyethylene (POE) moiety, such  as polysorbate surfactants, POE fatty acid esters, and POE  alkyl ethers, because the active agent is incompatible with  such surface active agents. For example, the active agent  pimecrolimus is not stable the presence of POE moieties, yet  benefits greatly from the use of dicarboxylic esters as pen› etration enhancers. In such cases, alternative surface active  agents are employed. In an exemplary manner, POE-free  surfactants include non-ethoxylated sorbitan esters, such as  sorbitan monopalmitate, sorbitan monostearate, sorbitan  tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan  monolaurate and sorbitan sesquioleate; glycerol fatty acid  esters,  such  as  glycerol  monostearate  and  glycerol  monooleate; mono-, di- and tri-esters of sucrose with fatty  acids ( sucrose esters), sucrose stearate, sucrose distearate  sucrose palmitate and sucrose laurate; and alkyl polyglyco› sides, such as lauryl diglucoside.  In one or more embodiments, the surface-active agent  includes mono-, di- and tri-esters of sucrose with fatty acids  (sucrose esters), prepared from sucrose and esters of fatty 40  acids or by extraction from sucro-glycerides. Suitable sucrose  esters include those having high monoester content, which  have higher HLB values.  In one or more preferred embodiments of the present  invention the surfactant includes at least one surfactant  selected from a polyoxyethylene fatty ether, a polyoxyethyl› ene fatty ester, a carbohydrate ester and a sucrose ester.  In one or more embodiments non limiting examples of  non-ionic surfactants include steareth-2, steareth-20, ste› areth-21, ceteareth 2, PEG-100 stearyl ether, cetearyl gluco- side, methyl glucose sesquistearate, sorbitan monostearate,  GMS NE and span 20.  In one or more embodiments non limiting other examples  of surfactant combinations are glyceryl stearate and PEG 100  stearate and laureth4; steareth 2, PEG 100 searate and !au- reth4; and cetearyl glucoside and cetearyl alcohol.  In an embodiment the surfactant containing formulations  are further boosted by a foam adjuvant for example stearyl  alcohol.  A non limiting example of a combination of surfactants  having a weighted average of their HLB values of 11 is  Glyceryl Stearate and PEG-100 Stearate (for example trade  name "simulsol 165" from Sepic ).  Hydrophobic Solvent  Optionally, the foamable carrier further contains at least  one hydrophobic solvent. The identification of a "hydropho› bic solvent", as used herein, is not intended to characterize the  FoamAdjuvant  Pharmaceutical compositions of the present invention may  in one or more embodiments usefully comprise in addition a  humectant or a moisturizer or combinations thereof.  Optionally, a foam adjuvant is included in the foamable  carriers of the present invention to increase the foaming  capacity of surfactants and/or to stabilize the foam. In one or  more embodiments of the present invention, the foam adju› vant agent includes fatty alcohols having 15 or more carbons  in their carbon chain, such as cetyl alcohol and stearyl alcohol  ( or mixtures thereof). Other examples of fatty alcohols are  arachidyl alcohol (C20), behenyl alcohol (C22), l-triacon- tanol (C30), as well as alcohols with longer carbon chains (up  to C50). Fatty alcohols, derived from beeswax and including  a mixture of alcohols, a majority of which has at least 20  A moisturizer, is a substance that helps retain moisture or  add back moisture to the skin. Examples are allantoin, petro› latum, urea, lactic acid, sodium PCV, glycerin, shea butter,  caprylic/capric/stearic triglyceride, candelilla wax, propy› lene glycol, lanolin, hydrogenated oils, squalene, sodium  hyaluronate and lysine PCA. Glycerine and sodium pCA  work in combination. Other examples may be found in the  Handbook of Pharmaceutical Additives  published by Gower.  A humectant, is a substance that helps retain moisture and  also prevents rapid evaporation. Non limiting examples of  suitable heumectants are propylene glycol, propylene glycol  derivatives, and glycerin. Other examples ofhumectants and  moisturizers may be found in the Handbook of Pharmaceuti› cal Additives published by Gower. Suitable ones for use with  and soluble in the waterless compositions of the present  invention may be selected as will be appreciated by a person  skilled in the art.  Moisturizers  In one or more embodiments, the hydrophobic organic  carrier is an oil, such as mineral oil, isopropyl palmitate,  isopropyl isostearate, diisopropyl adipate, diisopropyl dime› rate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl  ricinoleate, tocopheryl acetate, acetylated lanolin alcohol,  cetyl acetate, phenyl trimethicone, glyceryl oleate, toco› pheryl linoleate, wheat germ glycerides, arachidyl propi› onate, myristyl lactate, decyl oleate, propylene glycol ricino› leate,  isopropyl  lanolate,  pentaerythrityl  tetrastearate,  neopentylglycol  dicaprylate/dicaprate,  isononyl  isononanoate, isotridecyl isononanoate, myristyl myristate,  triisocetyl citrate, octyl dodecanol, unsaturated or polyun› saturated oils, such as olive oil, corn oil, soybean oil, canola  oil, cottonseed oil, coconut oil, sesame oil, sunflower oil,  borage seed oil, syzigium aromaticum oil, hempseed oil,  herring oil, cod-liver oil, salmon oil, flaxseed oil, wheat germ  oil, evening primrose oils; essential oils; and silicone oils,  such as dimethicone, cyclomethicone, polyalkyl siloxanes,  polyaryl siloxanes, polyalkylaryl siloxanes and polyether  siloxane copolymers, polydimethylsiloxanes ( dimethicones)  and  poly( dimethylsiloxane )-( diphenyl-siloxane)  copoly› mers. In one or more further embodiments the hydrophobic  organic carrier is petrolatum.  Humectant  A "hydrophobic solvent" as used herein refers to a material  having solubility in distilled water at ambient temperature of  less than about 1 gm per 100 mL, more preferable less than  about 0.5  gm per 100 mL, and most preferably less than about  0.lgmperl00mL.  solubilization capabilities of the solvent for any specific  active agent or any other component of the foamable compo› sition. Rather, such information is provided to aid in the  identification of materials suitable for use as a part in the  foamable compositions described herein.  US 8,795,693 B2  32  31 