US 2013 0123320A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0123320 A1 Chervinsky (43) Pub. Date: May 16, 2013

(54) TOPICAL COMPOSITION FOR PAIN RELIEF Publication Classification (51) Int. Cl. (76) Inventor: Alex Chervinsky, Brooklyn, NY (US) A6IPA613 29/00 L/45 38:8:2006.O1 A6IP 23/02 (2006.01) (52) U.S. Cl. (21) Appl. No.: 13/295,142 USPC ...... 514/.401 (57) ABSTRACT Described is a topically applied composition relief of pain. Also described are methods of preparing the composition and (22) Filed: Nov. 14, 2011 methods of using the composition to relieve pain. US 2013/O123320 A1 May 16, 2013

TOPCAL COMPOSITION FOR PAN RELIEF problems of maintaining the analgesic in Suspension within the solution of the topical pain reliever. Further, topical pain BACKGROUND OF THE INVENTION relievers have been known to have a delayed onset of action 0001 1. Field of the Invention after they have been applied to the integument or skin. Several 0002 The present invention relates to compositions and reasons may cause such a result, for example the topical pain methods for pain relief. reliever may not effectively permeate the skin. 0003 2. Description of the Related Art 0011 Many patients with localized pain due to arthritis, 0004 Pain results from the noxious stimulation of nerve bursitis, sprain or muscle strain, bruises or hematomas cannot endings. Nociceptive pain is caused by stimulation of noci tolerate conventional NSAIDS. In addition, topical adminis ceptors (e.g., a needle Stick or skin pinch), which then trans tration of conventional NSAIDS has been known to be inef mit impulses over neural pathways to the spinal neurons and fective because only a therapeutically ineffective amount of then to the brain. Neuropathic pain is caused by damage to the drug can penetrate the skin. In addition, indications such neural structures, such as peripheral nerve endings or nocice as acne, psoriasis and eczema are typically refractory to topi ptors, which can generate impulses in the absence of Stimu cal or oral administration of NSAIDS. lation (e.g., herpes Zoster pain after the rash has healed). 0012. In addition, joint pain can often indicate the onset of 0005. In contrast to pain treatment with systemic agents, a condition called osteoarthritis. Osteoarthritis is a degenera pain can be treated locally by topically administering a pain tive joint disease affecting articular cartilage developing in relieving agent directly to the painful area to block the noci the fourth and fifth decades of life that was initially believed ceptive mechanistic pathway. Local anesthetics prevent the to be a disease of wear and tear due to mechanical stress on the generation and conduction of nociceptive nerve impulses. joints. It is now known that the pathology of osteoarthritis is Thus, for example, a local anesthetic or analgesic can be not entirely mechanical and involves changes in the joint topically applied at the pain area. Advantages oftopical anes metabolism. Specifically, altered glucosamine metabolism thetic or analgesic administration over systemic administra appears to play a key role in the development of osteoarthritis. tion of pain relievers include decrease or preclusion of certain 0013. An effective treatment of osteoarthritis must address side effects, improved patient compliance, and reversible two types of problems: (i) pain, and joint tenderness, Swelling action (i.e., the action can be reversed by removing the anes and stiffness must be alleviated as an immediate patients thetic from the application site). problem; and (ii) the degenerative process must be stopped 0006 A variety of drug classes have anesthetic or analge preferably at its earlier stages. Treatment with anti-rheumat sic properties and can be administered in topical formula ics and NSAIDs has not proven successful. Anti-rheumatics, tions. Traditional local anesthetics or Sodium-channel block although quickly effective, were recently shown to impair the ers, such as lidocaine prevent the generation and conduction very function that physicians were trying to improve, and of nerve impulses by decreasing or preventing the large tran anti-inflammatory drugs alleviate the pain but do not address sient increase in the permeability of excitable membranes to the underlying degenerative disorder. Na+. Other agents with analgesic properties include the non 0014. Therefore, what is needed is a topical composition steroidal anti-inflammatories (“NSAIDs) and opioids, such that provides effective pain relief, is stable for long periods of as morphine. time and provides a long shelf-life, and avoids the disadvan 0007. It is common practice to provide a topical pain tages associated with other topical analgesics or systemically reliever using the well-known NSAID, salicylic acid (aspi administered drugs. What is further needed is a composition rin). Aspirin has been used effectively for many years in the that is effective in treating a wide variety of inflammatory medical and Scientific community as a pain reliever. Despite conditions by topical application of the composition. its benefits, systemic administration of aspirin has been 0015 These advantageous properties are provided by the shown to cause certain side effects in its users, for example composition set forth in the description that follows. Further stomach irritation and other internal problems associated advantages will be apparent from the description, or may be with ingesting aspirin. realized by the practice of the invention without undue experi 0008. Applying an aspirin solution topically to a user's mentation. skin, thereby avoiding the need for a user to ingest aspirin, has SUMMARY OF THE INVENTION been shown to be an effective manner of gaining the benefits of aspirin without the potential side effects. However, there 0016. The subject invention concerns a composition are difficulties associated with the ability to achieve a safe and which can be topically applied to the skin for the relief of pain stable form of a topical pain reliever containing aspirin that at the site of application. An embodiment of a composition will remain in suspension within the solution of the topical according to the invention comprises an effective amount of pain reliever. at least one anti-spasmodic or GABA-agonist, at least one 0009. In view of these difficulties, other NSAIDs have local anesthetic agent, at least one C2-adrenergic agonist, at been utilized for their anti-inflammatory or analgesic proper least one NMDA-receptor antagonist, at least one Non-Ste ties. It is an important aspect of any NSAID-based topical roidal Anti-inflammatory Drug (NSAID), at least one seroto pain reliever to permeate the necessary layers of the integu nin-norepinephrine reuptake inhibitor (SNRI), together with ment or skin in order to relieve pain without adversely affect a solvent in a cream or ointment base. ing vital internal organs. Accordingly, it is accepted that an 0017. A preferred embodiment for the composition of the effective topical pain reliever should be in the form that dis Subject invention comprises, in a cream or ointment base Solves the analgesic agents and transports it to the area of pain (inactive pharmaceutical compounding base): where it can then permeate the integument or skin to provide 0.018 about 1-20% anti-spasmodic or GABA-agonist effective relief. 0.019 about 1-5% local anesthetic agent 0010 Topical pain relievers have been introduced in the 0020 about 0.1-1.0% C-adrenergic agonist past, but such topical pain relievers have traditionally had 0021 about 1-20% NMDA-receptor antagonist US 2013/O123320 A1 May 16, 2013

0022 about 1-20% Non-Steroidal Anti-inflammatory 0054. It is therefore an object of the present invention to Drug (NSAID) provide a composition and method for the topical or transder 0023 about 1-10% Serotonin-Norepinephrine mal relief of pain to provide immediate, long-lasting and Reuptake Inhibitor (SNRI), and cumulative relief from pain and inflammation of Sore or 0024 about 1-10% solvent. stressed muscles and joints. 0025. The cream or ointment pharmaceutical compound 0055. It is yet another object of the present invention to ing base can comprise about 25% to about 75% (w/w) of the provide a pain relief composition comprising a plurality of composition, and preferably comprises about 50% to about Active Pharmaceutical Ingredients, which is effective and 60% of the composition. comfortable to apply to the skin. 0026. In a more preferred embodiment, the subject com 0056. It is yet another object of the present invention to position comprises, in a cream or ointment base: provide a soothing, anti-inflammatory complex for the joints 0027 gabapentin—1-10% (anti-spasmodic or GABA and muscles, which can be used in combination with other agonist pain relief agents. 0028 baclofen-1-10% (anti-spasmodic or GABA 0057. Other objects and advantages of the present inven agonist) tion will be apparent from a review of the following specifi 0029 lidocaine HC1–1-10% (local anesthetic agent) cation. 0030 clonidine HC1 0.1-1.0% (C2-adrenergic ago nist) DETAILED DESCRIPTION 0031 ketamine HC1–1-20% (NMDA-receptor 0058. The detailed description set forth below is intended antagonist) as a description of exemplary embodiments and is not 0032 ketoprofen-1-20% (NSAID) intended to represent the only forms in which the exemplary 0033 amitriptyline HC1–1-10% (SNRI) embodiments may be constructed and/or utilized. The 0034) DMSO–1-10% (solvent) description sets forth the functions and the sequence of steps 0035. The above ingredients are preferably mixed with or for preparation and/or use of the exemplary embodiments. into a pharmaceutical compounding base, such as PENcream, However, it is to be understood that the same or equivalent which makes up the balance of the composition, and typically functions and sequences which may be accomplished by dif comprises about 50-60% of the composition. ferent exemplary methods are also intended to be encom 0036. In a most preferred embodiment, a composition of passed within the spirit and scope of the invention. the Subject invention comprises: 0059. As used herein, “safe and effective amount’ means 0037 gabapentin 5% a Sufficient amount of a compound, composition or other 0038 baclofen 4% material described by this phrase to significantly induce a 0039 lidocaine 5% positive modification in the condition being treated, but low 0040 clonidine 0.2% enough to avoid undue side effects (e.g., significant skin 0041 ketamine-10% irritation or sensitization), within the scope of Sound judg 0042 ketoprofen 10% ment of the skilled person. The safe and effective amount of 0043 amitriptyline 2% the compound, composition or other material may vary with 0044) DMSO 5% the particular person being treated, factoring the age and 0045 PENcream base 58.8% physical condition of the biological Subject being treated, the 0046. The subject invention further comprises a method of severity of the condition, the duration of treatment, the nature preparing the disclosed embodiments of the composition. For of concurrent therapy, the specific compound, composition, example, the process comprises the following steps: or other material employed, the particular carrier utilized, and 0047 1. adding all active pharmaceutical ingredients the factors within the knowledge and expertise of the skilled (APIs) in a single vessel; person. 0048 2. adding to the APIs about 75% of the final 0060 A composition according to the subject invention amount of compounding base; comprises the following active pharmaceutical ingredients 0049. 3. adding the solvent (e.g., DMSO) to the APIs in (APIs): 75% compounding base; 0061 1. At least one anti-spasmodic or GABA-agonist. 0050. 4. mixing the APIs in 75% compounding base and A preferred embodiment of the subject composition Solvent for about 2 minutes using a mixer at relatively comprises two anti-spasmodic or GABA-agonist APIs, high speed (e.g., level 9 of 10); most preferably gabapentin and baclofen. Gabapentin 0051 5. adding the remaining about 25% of the com powder and baclofen, USP are available commercially pounding base to form a final mixture; from Medisca (Plattsburg, N.Y.). Examples of other 0.052 6. mixing the final mixture using a mixer until the anti-spasmodics or GABA-agonists that can be used in a mixture is Substantially homogenous, typically for about composition of the Subject invention include, but are not 7 minutes at high speed (level 9 of 10). limited to: Acamprosate, Picamilon, GHB, benzodiaz 0053. The subject invention further comprises a method of epines, nonbenzodiazepines (e.g., Zolpidem, Zopiclone, using the composition, for example, topically applying a safe Zaleplon), barbiturates, methaqualone, muscimol, pro and effective amount of the composition to the skin for the gabide, and tiagabine, or salts, derivatives, isomers, treatment of pain caused by joint stiffness, arthritis, Swelling, polymorphs, or esters thereof. Inflammation or edema, muscle cramps or tremors, or for 0062. 2. At least one local anesthetic agent. A preferred relief of discomfort from sensations such as a “burning embodiment of the Subject composition comprises sensation or pain, or unspecified tingling sensations in limbs lidocaine, more preferably lidocaine HCl monohydrate, or hands or feet. An effective amount is typically an amount to in the form of a solid powder as a local anesthetic com cover the area experiencing the pain or sensation. ponent of the subject composition. Lidocaine HC1 US 2013/O123320 A1 May 16, 2013

monohydrate is commercially available from Medisca limited to: the Salicylates—aspirin (acetylsalicylic (Plattsburg, N.Y.). Examples of other local anesthetics acid), Diflunisal, or Salsalate; the p-amino phenol that can be used in a composition of the Subject invention derivatives—Paracetamol, or phenacetin; the Propionic include, but are not limited to: local anesthetic esters, acid derivatives ibuprofen, Naproxen, Fenoprofen, selected from the group Procaine, Benzocaine, Chloro Flurbiprofen, Oxaprozin, or Loxoprofen; the Acetic acid procaine, Cocaine, Cyclomethycaine, Dimethocaine/ derivatives—indomethacin, Sulindac, Etodolac, Larocaine, Piperocaine, Propoxycaine, Procaine/No Ketorolac, Diclofenac, or Nabumetone; theEnolic acid Vocaine, Proparacaine. and Tetracaine/Amethocaine; (Oxicam) derivatives—piroXicam, Meloxicam, Tenoxi local anesthetic Amides, selected from the group Artic cam, Droxicam, Lornoxicam, or Isoxicam, the Fenamic aine, Bupivacaine, Cinchocaine/Dibucaine, Etidocaine, acid derivatives (Fenamates)—mefenamic acid, Levobupivacaine, Lidocaine/Lignocaine, Mepivacaine, Meclofenamic acid, Flufenamic acid, or Tolfenamic Prilocaine, Ropivacaine, Trimecaine; salts, derivatives, acid; the Selective COX-2 inhibitors (Coxibs)—cele isomers, polymorphs, or esters thereof, or combinations coxib, Parecoxib, or Firocoxib; or salts, derivatives, iso thereof. mers, polymorphs, or esters thereof. 0063. 3. At least one O-adrenergic agonist. A preferred 0.066 6. At least one serotonin-norepinephrine reuptake embodiment of the Subject composition comprises inhibitor (SNRI). A preferred embodiment of the subject clonidine, preferably clonidine HCl as an O-adrenergic composition comprises amitriptyline, preferably ami agonist component of the Subject composition. Cloni triptyline HCl as an SNRI component of the subject dine HCl, USP, is commercially available from Medisca composition. Amitriptyline HCl, USP, is commercially (Plattsburg, N.Y.). Examples of other C.-adrenergic available from Medisca (Plattsburg, N.Y.). Examples of agonists that can be used in accordance with the Subject other SNRIs s that can be used in accordance with the composition include, but are not limited to: Guanfacine, subject composition include, but are not limited to: Ven GuanabenZ, Guanoxabenz (a metabolite of guanabenz), lafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Guanethidine, Xylazine, Tizanidine, Methyldopa, and Levomilnacipran, Sibutramine, and Edivoxetine, or Fadolmidine, or the salts, derivatives, isomers, polymor salts, derivatives, isomers, polymorphs, or esters phs, or esters thereof. Other agents that classified as thereof. C.-adrenergic agonists but which have not been deter 0067. The subject composition further includes a solvent. mined as C.- or O-adrenergic agonists include: Preferably a polar aprotic solvent, such as Dimethyl Sulfox amidephrine, amitraz, anisodamine, apraclonidine, bri ide (DMSO) can be used in the composition of the subject monidine, cirazoline, detomidine, dexmedetomidine, invention. DMSO is commercially available from Medisca epinephrine, ergotamine, etilefrine, indanidine, lofexi (Plattsburg, N.Y.). Other polar aprotic solvents in this class dine, medetomidine, mephentermine, metaraminol, include dimethylformamide, dimethylacetamide, N-methyl methoxamine, mivaZerol, naphazoline, norepinephrine, 2-pyrrolidone, and HMPA. norfenefrine, octopamine, oxymetazoline, phenylpro 0068. The active components (1.-6., listed above) and sol panolamine, rillmenidine, romifidine, Synephrine, tal vent are formulated in a pharmaceutical compounding base, ipexole, and tizanidine, or salts, derivatives, isomers, such as PENcream. PENcream is commercially available polymorphs, or esters thereof. To the extent these agents from HUMCO (Texarkana, Tex.). Pharmaceutical com are identified as C-adrenergic agonists, they may be pounding bases are well known in the art, and other pharma substituted for clonidine HCl in a composition of the ceutical compounding bases may be freely Substituted for Subject invention. PENcream. 0064. 4. At least one NMDA-receptor antagonist. A pre 0069. A topical composition prepared in accordance with ferred embodiment of the subject composition com the present invention may comprise other skin benefiting or prises ketamine, preferably ketamine HCl as an NMDA carrier components, including, but not limited to conditioning receptor antagonist component of the Subject agents, skin protectants, antioxidants, viscosity modifying composition. Ketamine HCl, USP, is commercially agents, film formers, emollients, Surfactants, solubilizing available from Medisca (Plattsburg, N.Y.). Examples of agents, preservatives, fragrance, chelating agents, foaming or other NMDA-receptor antagonists that can be used in antifoaming agents, opacifying agents, stabilizing agents, pH accordance with the Subject composition include, but are adjustors, absorbents, anti-caking agents, slip modifiers, vari not limited to: Amantadine, Phencyclidine (PCP), Dex ous solvents, solubilizing agents, denaturants, bulking tromethorphan or dextrorphan, Memantine, Riluzole, agents, emulsion stabilizing agents, Suspending agents, colo HU-211 (also a cannabinoid), Conantokins, or the dual rants, binders, conditioning agent-emollients, surfactant opioids and NMDA-Antagonists: Ketobemidone, emulsifying agents, biological products, cosmetic soothing Methadone, Dextropropoxyphene, Tramadol, Kratom alkaloids, or Ibogaine. These compounds can also be aids, and/or combinations thereof. used as the salts, derivatives, isomers, polymorphs, or 0070 Emollients that can be used in the subject composi esters thereof. tion include, but are not limited to, the following: 0065 5. At least one Non-Steroidal Anti-inflammatory 0071 1. Triglyceride esters which include, but are not Drug (NSAID). A preferred embodiment of the subject limited to, vegetable and animal fats and oils such as composition comprises ketoprofen, preferably ketopro palm oil, castor oil, cocoa butter, safflower oil, cotton fen HCl as an NMDA-receptor antagonist component of seed oil, corn oil, olive oil, cod liver oil, almond oil, the subject composition. Ketoprofen HCl, USP, is com avocado oil, palm oil, Sesame oil, squalene, kikui oil and mercially available from Letco Medical (Decatur, Ala.). Soybean oil; Examples of other NSAIDs that can be used in accor 0.072 2. Acetoglyceride esters, including but not lim dance with the Subject composition include, but are not ited to acetylated monoglycerides; US 2013/O123320 A1 May 16, 2013

0073. 3. Ethoxylated glycerides such as ethoxylated 0097. A preferred embodiment of the final composition glyceryl monostearate; comprises, in weight percent: gabapentin—5%; baclofen 0074. 4. Alkyl esters of fatty acids having 10 to 20 4%; lidocaine—5%: clonidine 0.2%; ketamine—10%: carbon atoms which include, but are not limited to, ketoprofen 10%; amitriptyline 2%; DMSO–5%, and methyl, isopropyl and butyl esters of fatty acids; PENcream base 58.8%. (0075 5. Alkenyl esters of fatty acids having 10 to 20 0098. The final composition can then be placed into an carbonatoms Such as oleyl myristate, oleyl Stearate, and appropriate container and/or packaging for shipping and stor oleyl oleate; age. The packaging can include listings of ingredients and 0076 6. Fatty acids having 10 to 20 carbon atoms such instructions for use. as pelargonic, lauric, myristic, palmitic, Stearic, isos 0099. A composition according to the subject invention tearic, hydroxy Stearic, oleic, linoleic, ricinoleic, can be topically applied. Typically, a safe and effective arachidic, behenic, and erucic acids; amount of the composition is applied to the skin for the (0077 7. Fatty alcohols having 10 to 20 carbon atoms treatment of pain caused by joint stiffness, arthritis, Swelling, Such as lauryl, myristyl, cetyl, hexadecyl, Stearyl, isos Inflammation or edema, muscle cramps or tremors, or for tearyl, hydroxy Stearyl, oleyl, ricinoleyl, behenyl, erucyl, relief of discomfort from sensations such as a “burning and 2-octyl dodecanyl alcohols; sensation or pain, or unspecified tingling sensations in limbs 0078 8. Lanolin and lanolin derivatives including, but or hands or feet. A safe and effective amount is typically an not limited to lanolin, lanolin oil, lanolin wax, lanolin amount (1-5 g) which can be spread onto and cover the alcohols, lanolin fatty acids, isopropyllanolate, ethoxy specific area experiencing the pain or sensation. lated cholesterol and lanolin alcohols; 1. A topical composition for pain relief, said composition 0079 9. Polyhydric alcohol esters, including but not comprising: limited to, ethylene glycol mono and di-fatty acid esters, about 1-20% of at least one anti-spasmodic or GABA diethylene glycol mono-and di-fatty acid esters and agonist polyethylene glycol (200-6000) mono- and di-fatty acid esters; about 1-5% of at least one local anesthetic agent 0080 10. Wax esters such as beeswax, spermaceti, about 0.1-1.0% of at least one C2-adrenergic agonist myristyl myristate, Stearyl Stearate; about 1-20% of at least one NMDA-receptor antagonist I0081. 11. Beeswax derivatives including but not limited about 1-20% of at least one Non-Steroidal Anti-inflamma to, polyoxyethylene sorbitol beeswax, tory Drug (NSAID) I0082) 12. Vegetable waxes including, but not limited to, about 1-10% of at least one Serotonin-Norepinephrine carnauba and candelilla waxes; Reuptake Inhibitor (SNRI), and I0083 13. Phospholipids such as lecithin and deriva about 1-10% of at least one solvent, and tives; about 25-75% of at least one pharmaceutical compounding I0084. 14. Sterols including, but not limited to, choles base. terol and cholesterol fatty acid esters; and 2. The topical composition of claim 1, wherein said anti I0085 15. Amides such as fatty acid amides, ethoxylated spasmodic or GABA-agonist is gabapentin or baclofen, or a fatty acid amides, and solid fatty acid alkanolamides. combination of gabapentin and baclofen. I0086. In the manufacture of a preferred embodiment of a 3. The topical composition of claim 2, wherein said com composition of the Subject invention, a formulation includes: position comprises a combination of gabapentin and I0087 Gabapentin powder 22.7g baclofen, said gabapentin comprising about 5% and said I0088 Baclofen, USP powder 18.16 g baclofen comprising about 4% of said composition. I0089 Lidocaine HCl monohydrate, USP 22.7g 4. The topical composition of claim 1, wherein said local 0090. Clonidine HCl, USP 0.908 g anesthetic agent is lidocaine. (0091 Ketamine HC1 monohydrate, USP powder 45.4 5. The topical composition of claim 4, wherein said 9. lidocaine is lidocaine HCl monohydrate and comprises about 0092 Ketoprofen USP powder 45.4g 5% of said composition. 6. The topical composition of claim 1, wherein said O-adr (0093. Amitriptyline HCl, USP 9.08 g energic agonist is clonidine. 0094) DMSO (reagent grade) ACS liquid 22.7 ml, and 7. The topical composition of claim 6, wherein said cloni (0095 PENcream base 266.952g. dine is clonidine HCl and comprises about 0.2% of said 0096. The above components are weighed and each of the composition. pre-weighed active ingredient powders (gabapentin, baclofen, lidocaine, clonidine, ketamine, ketoprofen, and 8. The topical composition of claim 1, wherein said amitriptyline) are added to a mixing vessel for a commercial NMDA-receptor antagonist is ketamine. mixer. About 75% of the pre-weighed PENcream compound 9. The topical composition of claim 8, wherein said ket ing base (approximately 200g), and the entire amount of the amine is ketamine HCl monohydrate and comprises about DMSO solvent, is added to the active ingredient powders in 10% of said composition. the mixing vessel. The active ingredient powders, solvent and 10. The topical composition of claim 1, wherein said Non compounding base are mixed for about 2 minutes at a mixing Steroidal Anti-inflammatory Drug (NSAID) is ketoprofen. speed level of 9. The remaining 25% of the compounding 11. The topical composition of claim 10, wherein said base (approximately 67 g) is then added to provide a final ketoprofen comprises about 10% of said composition. mixture. The final mixture is mixed for about 7 minutes at a 12. The topical composition of claim 1, wherein said Sero mixing speed level of 9 until the final mixture is substantially tonin-Norepinephrine Reuptake Inhibitor (SNRI) is amitrip homogeneous, forming the final composition. tyline. US 2013/O123320 A1 May 16, 2013

13. The topical composition of claim 12, wherein the ami 20. A method of preparing a composition of claim 1, triptyline is amitriptyline HCl and comprises about 2% of wherein said method comprises the steps of: said composition. Pre-weighing or pre-measuring Gabapentin powder 22.7 14. The composition of claim 1 wherein said solvent is g; Baclofen, USP, powder 18.16 g; Lidocaine HCl DMSO. monohydrate, USP 22.7 g; Clonidine HCl, USP 0. 15. The composition of claim 14 wherein said DMSO 908 g; Ketamine HCl monohydrate, USP powder 45.4 comprises about 5% of said composition. g; Ketoprofen USP powder 45.4 g; Amitriptyline HCl, 16. The composition of claim 1, wherein said pharmaceu USP 9.08 g; DMSO (reagent grade) ACS liquid 22.7 tical compounding base is PENcream. ml, and PENcream base 266.952 g; 17. The composition of claim 16, wherein said PENcream Adding to a mixing vessel the pre-weighed Gabapentin comprises about 58.8% of said composition. powder, Baclofen powder, Lidocaine HCl monohydrate, 18. A method for relieving pain, said method comprising: Clonidine HCl, Ketamine HCl monohydrate, Ketopro Providing a topical composition of claim 1, fen powder, and Amitriptyline HCl, with about 75% of Topically applying an effective amount of said composi the pre-weighed pharmaceutical compounding base and tion to the skin at a site of pain or discomfort, and 100% of the pre-measured DMSO; Optionally, repeating as needed. 19. The method of claim 18, wherein said composition Mixing for about 2 minutes to form a mixture; comprises: gabapentin—5%; baclofen 4%; lidocaine— Adding a remaining about 25% of said compounding base 5%; clonidine 0.2%; ketamine—10%; ketoprofen 10%: to said mixture, and mixing for about 7 minutes to form amitriptyline 2%; DMSO–5%, and PENcream base-58. a homogeneous final mixture. 8%. k k k k k