Method for developing a liquid composition to be applied to the skin as a foam and a composition that can be applied topically

Abstract

A liquid pharmaceutical composition to be applied to the skin as a foam and that has at least one solvent, at least one active pharmaceutical ingredient, and at least one foaming agent. The foam volume and the foam stability are determined according to a standardized SITA measuring method. The foaming agent, the solvent, and the active pharmaceutical ingredient are varied in regard to the chemical type and/or concentration thereof until the foam thus produced by the SITA measuring method has a foam volume of at least 400 ml and such foam stability that after a dwell time of up to ten minutes the foam still has at least 50% of the foam volume that originally existed immediately after the foam was produced.

1 - 52 . (canceled) 
     
     
         53 . A composition suitable for topical use comprising at least one systemically and/or topically acting pharmaceutical active ingredient, wherein the composition in addition to the pharmaceutical active ingredient also contains at least one solvent as well as at least one foaming agent and has such a fluid consistency that it forms a foam when applied, wherein:
 a) the at least one foaming agent contained in the liquid composition is a phospholipidic foaming agent; 
 b) the at least one phospholipid foaming agent, the at least one solvent and the at least one active ingredient are attuned to each other in their chemical nature and/or their concentration so that the composition can be mechanically foamed without the use of an additional propellant; 
 c) by mechanically foaming of 250 ml of the liquid composition a foam is created having a foam volume of at least 400 ml and a foam stability after a dwell time of up to ten minutes of at least 50% of the foam volume that was originally present immediately after the creation of the foam; and 
 d) both the foam volume and the foam stability are determined by a standardized SITA foam measurement method. 
 
     
     
         54 . The composition according to claim  1 , wherein the foam volume is between 450 and 1400 ml and the foam stability is between 55% and 100%. 
     
     
         55 . The composition according to  claim 53 , wherein the foam has a density between 0.05 g/ml and 0.8 g/ml. 
     
     
         56 . The composition according to  claim 53 , wherein the composition contains as solvent such a solvent selected from the group consisting of water, alcohol, especially monovalent to trivalent alcohol, polyalcohol, and mixtures thereof. 
     
     
         57 . The composition according to  claim 53 , wherein the at least one active ingredient is an active ingredient for use on humans or animals and is selected from the group consisting of local anesthetics, anti-allergic agents, dermatics, active ingredients against flu infections and colds, active ingredients for the treatment of neuropathies, active ingredients for the treatment of disturbed circulation, chemotherapy drugs, quinine, antimycotics, antibiotics, thalidomide, serotonin, eicosanoids, analgesics, anticonvulsants, nonsteroidal antirrheumatics, leukotrienes, leukotriene inhibitors, androgens, antiandrogens, corticoids, opiate receptor antagonists, blood clotting inhibitory substances, thrombocyte aggregation inhibitors, histamine antagonists, regulatory and enzymatically acting peptides and proteins, nucleic acids (single and double-stranded DNA, single and double-stranded RNA, snRNA, DNA oligonucleotides, RNA oligonucleotides) and oligopeptides, antipruritics, antidiabetics, prostaglandins, prostaglandin synthesis inhibitors, antiviral-acting or virostatic-acting substances, antimicrobial-acting substances, active ingredients against prions, immune suppressants, hormones, active ingredients for treatment of warts or wounds, especially chronic wounds, vitamins, plant extracts or essences of plant extracts, psychoactive drugs, active ingredients influencing sleep, analeptics, general anesthetics, muscle relaxants, antiepileptics, antiparkinson agents, antiemetics, antiparasitics, ganglion-active ingredients, sympathetic-active ingredients, parasympathetic-active ingredients, antibacterial-acting drugs, calcium antagonists, cardiovascular agents, antiasthmatics, antitussives, expectorants, hepatics, diuretics, choleretics, disinfectants, trace elements, antiinfectives, cytostatics, antimetabolites, hormone antagonists, immune modulators, as well as derivates and salts of the aforementioned active ingredients. 
     
     
         58 . The composition according to  claim 53 , wherein the at least one pharmaceutical active ingredient is an analgesic active ingredient. 
     
     
         59 . The composition according to  claim 58 , wherein the analgesic active ingredient is selected from the group consisting of diclofenac, ketoprofen and ibuprofen. 
     
     
         60 . The composition according to  claim 58 , wherein the at least one analgesic is contained in the composition in a concentration between 0.1 wt. % and 20 wt. %. 
     
     
         61 . The composition according to  claim 53 , wherein the composition contains, as the phospholipidic foaming agent, a phosphatidyl choline isolated from soy beans, and the concentration of the phosphatidyl choline in the phospholipidic foaming agent is more than 50 wt. %, in relation to the dry substance of the phospholipidic foaming agent. 
     
     
         62 . The composition according to  claim 61 , wherein at most 15 wt. % of lyso-phosphatidyl choline, at most 10 wt. % of phosphatidic acid and at most 10 wt. % of phosphatidyl ethanolamine are contained in the phospholipidic foaming agent. 
     
     
         63 . The composition of  claim 61 , wherein the phosphatidyl choline contained in the phospholipidic foaming agent has an acid number of at most 10, a peroxide number of at most 10, and an oil concentration of at most 6 wt. %. 
     
     
         64 . The composition of  claim 53 , wherein the composition has the phospholipidic foaming agent in a concentration between 2 wt. % and 25 wt. %. 
     
     
         65 . A method for treatment of pain, inflammation, rheumatic diseases or acute trauma, comprising the application of a foam to the skin of a warm-blooded mammal created by mechanically foaming of a composition according to  claim 53  immediately prior to application, whereby the composition contains as active ingredient at least one analgesic. 
     
     
         66 . The method of  claim 65 , wherein the composition contains the analgesic in a concentration between 0.1 wt. % and 20 wt. %. 
     
     
         67 . A method for the development of a pharmaceutical composition to be applied as a foam to the skin according to  claim 53 , wherein the foamable liquid composition contains at least one solvent, at least one pharmaceutical active ingredient, and at least one phospholipidic foaming agent, wherein:
 a) the foam volume and the foam stability are determined by a standardized SITA measurement method without the use of a propellant; and   b) the at least one phospholipidic foaming agent, the at least one solvent and the at least one pharmaceutical active ingredient, contained in the liquid composition, are varied in regard to their chemical nature and/or concentration until the foam created by the SITA measurement method, using 250 ml of the liquid composition, has a foam volume of at least 400 ml and a foam stability that the foam still has, after a dwell time of up to ten minutes at least 50% of the foam volume that was originally present immediately after the creation of the foam.   
     
     
         68 . The method according to  claim 67 , wherein a correlation is produced between the foam as specified by the SITA measurement method and the pharmaceutical properties. 
     
     
         69 . The method according to  claim 67 , wherein a foam applicator is selected for the mechanical foaming of the liquid composition, a foam is created from the liquid composition by the selected foam applicator, and a correlation is produced between the properties, especially the pharmaceutical properties of the foam created via the foam applicator and the foam volume and/or the foam stability as determined via the SITA measurement method. 
     
     
         70 . The method according to  claim 67 , wherein such a foam is created from the liquid composition by the SITA foam measurement method that possess a foam density between 0.05 g/ml and 0.8 g/ml. 
     
     
         71 . The method according to  claim 67 , wherein the phospholipidic foaming agent is a phosphatidyl choline isolated from soy beans and that the concentration of the phosphatidyl choline in the phospholipidic foaming agent is more than 50 wt. %, in relation to the dry substance of the phospholipidic foaming agent.