US 2009019 1257A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0191257 A1 Smith (43) Pub. Date: Jul. 30, 2009

(54) PAIN RELIEF LOLLIPOP COMPOSITIONS Publication Classification AND METHODS (51) Int. Cl. A6IR 9/00 (2006.01) (75)75) InventorI tOr: Davidt J. Smith,mitn, San DLJ1ego, CA A6IP 25/04 (2006.01) (52) U.S. Cl...... 424/440 Correspondence Address: KNOBBE MARTENS OLSON & BEAR LLP (57) ABSTRACT 2040 MAINSTREET, FOURTEENTH FLOOR IRVINE, CA 92.614 (US) A pain relief lollipop comprises a candy matrix comprising 9 (a) an opioid agonist, (b) an N-methyl-D-aspartate receptor (73) Assignee: Innovative Pharmaceuticals, antagonist different from the opioid agonist, (c) gabapentin, LLC, San Diego, CA (US) or a pharmaceutically acceptable salt thereof, and, optionally, s s a muscle relaxant, sedative, anxiolytic, and/orantidepressant. (21) Appl. No.: 12/021,647 A patient can self-administer Small amounts of the pain relief drug as needed by simply licking or Sucking on the lollipop in (22) Filed: Jan. 29, 2008 response to his Subjective experience of pain. US 2009/019 1257 A1 Jul. 30, 2009

PAN RELEF LOLLIPOP COMPOSITIONS continuous basis. A patient may self-administer Small AND METHODS amounts of the pain relief drug as needed by simply licking or Sucking on the lollipop in response to his or her Subjective BACKGROUND OF THE INVENTION experience of pain. These significant advantages can be achieved by incorporating pain relief drugs into a candy mix 0001 1. Field of the Invention ture capable of being absorbed by the patient through the 0002 Embodiments of this invention relate to composi mucosal tissue of the mouth, pharynx and esophagus. The tions useful for alleviating pain and systems for their delivery candy and pain relief drug is molded into a lollipop form, to humans. Preferred embodiments relate to pain relief lolli which, as discussed more specifically hereinafter, may be pops that may be used to provide oral transmucosal delivery administered by the patient as needed for pain relief. of opioid agonists, NMDA receptor antagonists, and gabap 0007 Preferred pain relief drugs are opioid agonists. To entin, or a pharmaceutically acceptable salt thereof. inhibit the development of tolerance and/or addiction to the 0003 2. Description of the Related Art opioid agonists by the patient, preferred lollipops further 0004. The treatment of physical pain concerns health care comprise a substance that blocks the N-methyl-D-aspartate professionals throughout the world. The treatment of chronic receptor, herein referred to as an “NMDA receptor antago pain is particularly challenging because of the frequent need nist.” Preferred lollipops further comprise gabapentin, or a for repeated administration of pain relief medication. Chronic pharmaceutically acceptable salt thereof. In some embodi pain is generally considered to be pain that continues a month ments, lollipops also contain a muscle relaxant, a sedative, an or more beyond the usual recovery period for an illness or anxiolytic, and/or tricyclic antidepressant, to provide further injury or pain that goes on over months or years as a result of comfort and relief for the patient. a chronic condition. It may be continuous or come and go. It 0008. Some embodiments are directed to a pain relief lol is estimated that chronic pain disables, to Some degree, about lipop, comprising a candy matrix comprising (a) an opioid 86 million Americans. It is regarded as a source of frustration agonist, (b) an N-methyl-D-aspartate receptor antagonist dif for the health care professionals who care for the patient, and ferent from the opioid agonist, and (c) gabapentin or a phar affects the quality of life and economic security not only of maceutically acceptable salt thereof, and a holder in contact the person with pain, but also his or her family. It is estimated with the candy matrix. In some aspects, the opioid agonist is that United States business and industry loses about S90 selected from the group consisting of fentanyl, hydromor billion annually to sick time, reduced productivity, and direct phone, hydrocodone, ketamine, methadone, oxycodone, oxy medical and other benefit costs due to chronic pain among morphone, propoxyphene, Sulfentanil, and pharmaceutically employees. In some cases, repeated administration of the pain acceptable salts thereof. In some aspects, the N-methyl-D- relief medication causes sufferers of chronic pain to develop aspartate receptor antagonist is selected from the group con an undesirable tolerance or addiction, creating further health sisting of amantadine, D.L-2-amino-5-phosphono Valeric issues for the patient and additional challenges for the health acid, dextromethorphan, ketamine, methadone, and pharma care professional. ceutically acceptable salts thereof. 0005. There are a number of methods for administering 0009. Other embodiments are directed to a method for pain relief medications, including oral and parenteral (admin treating pain, comprising identifying a human Suffering from istered in a manner other than through the digestive tract). Oral administration is most frequently accomplished by for pain and administering a pain relief lollipop described in the mulating the pain relief medication into tablet or syrup and various embodiments herein. Some aspects of the embodi allowing the patient to swallow it. This method is simple, well ment are directed towards the treatment of chronic pain. accepted and relatively painless, but may be problematic for 0010 Still other embodiments are directed to a method for uncooperative patients. Also, there is often a considerable making a pain relieflollipop described in the various embodi lapse of time between administration of the pain relief medi ments herein, comprising intermixing the opioid agonist, cation and its therapeutic effect because of the time needed N-methyl-D-aspartate receptor antagonist, gabapentin or a for gastrointestinal absorption. This time lag is of particular pharmaceutically acceptable salt thereof, and candy matrix at concern when a patient is Suffering from severe or chronic a temperature effective to at least partially melt the candy pain. Faster administration may be accomplished by direct matrix to form an at least partially molten lollipop mixture, injection of the pain relief medication, but most people con molding the at least partially molten lollipop mixture to form sider the injection itself to be painful and thus undesirable. a molded lollipop mixture, contacting the molded lollipop What is needed is a method for administering a variety of pain mixture with a holder, and cooling the molded lollipop mix relief formulations that is fast, well tolerated and relatively ture to form a pain relief lollipop. painless. 0011. Other embodiments are directed to a method for making a pain relieflollipop described in the various embodi ments herein, comprising intermixing the opioid agonist, SUMMARY OF THE INVENTION N-methyl-D-aspartate receptor antagonist, gabapentin or a 0006 Preferred embodiments are directed towards pain pharmaceutically acceptable salt thereof and candy matrix at relief delivery systems and methods and, in particular, lolli a temperature effective to at least partially melt the candy pops and methods of using them for the relief of pain. Pre matrix to form an at least partially molten lollipop mixture, ferred lollipops are capable of introducing a pain relief drug molding the at least partially molten lollipop mixture to form into a patient's system faster than a pain relief drug taken a molded lollipop mixture, cooling the molded lollipop mix orally and without the pain and invasiveness of an injection. ture to forman at least partially hardened candy, and contact Unlike the ordinary oral ingestion of pain medication or injec ing the at least partially hardened candy with a holder to form tions where a relatively large dose is given intermittently, use a pain relief lollipop. of a pain relief lollipop may permit the patient to take rela 0012 Still other embodiments are directed to a pain relief tively small doses of pain relief medication on an almost lollipop, comprising a candy matrix comprising (a) an opioid US 2009/019 1257 A1 Jul. 30, 2009 agonist, (b) an N-methyl-D-aspartate receptor antagonist dif context, "opioid agonist' is used in the ordinary sense to refer ferent from the opioid agonist, and (c) gabapentin or a phar to opiates, opiate derivatives, opioids, and other substances maceutically acceptable salt thereof, and a means for holding whose effects are mediated by the same receptor, and includes the candy matrix. mixtures thereof. Non-limiting examples of preferred opioid 0013. Other embodiments are directed to a pain relieflol agonists include fentanyl, hydromorphone, hydrocodone, lipop, comprising a candy matrix comprising (a) an opioid ketamine, methadone, oxycodone, oxymorphone, pro agonist selected from the group consisting offentanyl, hydro poxyphene, Sulfentanil, and pharmaceutically acceptable morphone, hydrocodone, oxycodone, oxymorphone, pro salts thereof. poxyphene, Sulfentanil, and pharmaceutically acceptable 0017. The amount of opioid agonist in the lollipop is an salts thereof, (b) an N-methyl-D-aspartate receptor antago amount that is effective to reduce the patient's pain, and will nist selected from the group consisting of amantadine, dex generally vary depending on the type and amount of pain tromethorphan, and pharmaceutically acceptable salts experienced by the patient, the characteristics of the patient, thereof, and (c) gabapentin or a pharmaceutically acceptable and the efficacy of the particular opioid agonist. Dosages of salt thereof; and a holder in contact with the candy matrix. In particular opioid agonists useful for treating pain are known Some aspects, the candy matrix further comprises a muscle to those skilled in the art, see, e.g., Physician's Desk Refer relaxant, wherein the muscle relaxant can be selected from ence 2003, which is hereby incorporated by reference in its the group consisting of alprazolam, butalbital, clonazepam, entirety and particularly for the purpose of describing typical carisoprodol, diazepam, flexeril, lorazepam, methocarbamol. dosages of opioid agonists, NMDA receptor antagonists, and pharmaceutically acceptable salts thereof. In some muscle relaxants, sedatives, anxiolytics and antidepressants. aspects, the candy matrix further comprises a sedative, Dosages may also be determined by routine experimentation. wherein the sedative can be selected from the group consist Such known or determined dosages of opioid agonist may be ing of clonazepam, butalbital, diazepam, phenobarbital, and used as a guideline for determining the amount of opioid pharmaceutically acceptable salts thereof. In other aspects, agonist to include in the lollipop, typically taking into account the candy matrix further comprises an anxiolytic, wherein the various patient characteristics (e.g., level of pain, age, weight, anxiolytic can be selected from the group consisting of alpra and overall health) in a manner known to those skilled in the Zolam, clonazepam, diazepam, lorazepam, and pharmaceuti medical arts, as well as the characteristics of the lollipop (e.g., cally acceptable salts thereof. In still other aspects, the candy rate of dissolution) and the transmucosal delivery character matrix further comprises an antidepressant, wherein the anti istics of the particular opioid agonist. depressant can be a tricyclic antidepressant selected from the (0018 To avoid or reduce the development of tolerance group consisting of amitriptyline, amoxapine, desipramine, and/or dependence by the patient on the opioid agonist, the doxepin, imipramine, maprotiline, nortriptyline, protrip lollipop candy preferably comprises an NMDA receptor tyline, trimipramine, and pharmaceutically acceptable salts antagonist different from the opioid agonist. NMDA receptor thereof. In yet other aspects, the candy matrix further com antagonists are substances known to those skilled in the art prises at least two different medicaments selected from the that block the N-methyl-D-aspartate receptor or that block a group consisting of a muscle relaxant, a sedative, an anxi major intracellular consequence of NMDA receptor activa olytic and a tricyclic antidepressant, wherein the muscle tion, see U.S. Pat. Nos. 5,321,012; 5,654,281 and 5,869,498, relaxant can be selected from the group consisting of alpra all of which are hereby incorporated by reference in their Zolam, butalbital, clonazepam, diazepam, flexeril, entireties, and particularly for the purpose of describing lorazepam, methocarbamol, and pharmaceutically accept NMDA receptor antagonists and their uses. The NMDA able salts thereof; in which the sedative can be selected from receptor antagonist may be a mixture. Non-limiting examples the group consisting of clonazepam, butalbital, diazepam, of preferred NMDA receptor antagonists for inclusion in the phenobarbital, and pharmaceutically acceptable salts thereof; lollipop include amantadine, D.L-2-amino-5-phosphono in which the anxiolytic can be selected from the group con sisting of alprazolam, clonazepam, diazepam, lorazepam, and Valeric acid, dextromethorphan, ketamine, methadone, and pharmaceutically acceptable salts thereof; and in which the pharmaceutically acceptable salts thereof. Since some Sub tricyclic antidepressant can be selected from the group con stances, e.g., ketamine and methadone, may be classified as sisting of amitriptyline, amoxapine, desipramine, doxepin, both opioid agonists and NMDA receptor antagonists, it is imipramine, maprotiline, nortriptyline, protriptyline, trimi understood that the opioidagonist in any particular lollipop is pramine, and pharmaceutically acceptable salts thereof. different from the NMDA receptor antagonist. 0019. The amount of NMDA receptor antagonist in the 0014. These and other embodiments are described in lollipop is an amount that is effective to avoid or reduce the greater detail below. development of tolerance and/or dependence by the patient DETAILED DESCRIPTION OF THE PREFERRED on the opioid agonist, and will generally vary depending on EMBODIMENTS the type and amount of the particular opioidagonist present in the lollipop and on the effectiveness of the particular NMDA 00.15 Preferred compositions provide lollipop composi receptor antagonist. Dosages of particular NMDA receptor tions and methods for using them to treat pain. In this context, antagonists useful for avoiding or reducing the development "lollipop' is used in its ordinary sense to refer to a piece of of tolerance and/or dependence to a particular opioid agonist candy in operable contact with a holder. Preferably, the candy are known to those skilled in the art, see, e.g., Physician's is supported by, held by, or attached to the holder to provide Desk Reference 2003, or may be determined by routine operable contact. Non-limiting examples of holders include a experimentation. Such known or determined dosages of Stick or string partially embedded in or attached to the candy, NMDA receptor antagonist may be used as a guideline for and a platform Such as a cone that Supports the candy. determining the amount of the NMDA receptor antagonist to 0016 To provide pain relief to the consumer of the lolli include in the lollipop, typically taking into account various pop, the candy preferably comprises an opioid agonist. In this patient characteristics (e.g., level of pain, age, weight, and US 2009/019 1257 A1 Jul. 30, 2009

overall health) in a manner known to those skilled in the cally acceptable salts thereof. Non-limiting examples of anti medical arts, as well as the characteristics of the lollipop (e.g., depressants include tricyclic antidepressants and monamine rate of dissolution) and the transmucosal delivery character oxidase inhibitors. Non-limiting examples of preferred tricy istics of the particular NMDA receptor antagonist. clic antidepressants include amitriptyline, amoxapine, 0020. To provide further relief from pain, especially desipramine, doxepin, imipramine, maprotiline, nortrip chronic pain, to the consumer of the lollipop, the candy pref tyline, protriptyline, trimipramine, and pharmaceutically erably comprises gabapentin, or a pharmaceutically accept acceptable salts thereof. Those skilled in the art recognize that able salt thereof. Gabapentin is an anti-convulsant originally Some Substances may have multiple classifications (e.g., developed for the treatment of epilepsy. The use of gabapen alprazolam as both a muscle relaxant and an anxiolytic). It is tin in the lollipop compositions described herein can comple therefore understood that reference herein to a lollipop that ment the use of opioid analgesics to provide more complete contains three or more medicaments selected from the group relief from neuropathic pain. consisting of opioid agonist, NMDA receptor antagonist, 0021. The amount of gabapentin, or a pharmaceutically muscle relaxant, sedative, anxiolytic and antidepressant, acceptable salt thereof, in the lollipop is an amount that is means that each of the three or more medicaments are differ effective to reduce the patient's pain, and will generally vary ent from one another. depending on the type and amount of pain experienced by the 0024. The amount and type of additional medicament patient, and the characteristics of the patient. Dosages of (e.g., muscle relaxant, sedative, anxiolytic and/or antidepres gabapentin useful for treating pain are known to those skilled Sant) in the lollipop, if any, is an amount that is effective to in the art, see, e.g., Physician's Desk Reference 2003, which provide additional comfort and/or relief to the patient from is hereby incorporated by reference in its entirety and particu various conditions, and will generally vary depending on the larly for the purpose of describing typical dosages of gabap type and amount of the particular additional medicament entin, opioid agonists, NMDA receptor antagonists, muscle present in the lollipop. Dosages of particular additional medi relaxants, sedatives, anxiolytics and antidepressants. Dos caments useful for treating various conditions are known to ages may also be determined by routine experimentation. those skilled in the art, see, e.g., Physician's Desk Reference Such known or determined dosages of gabapentin may be 2003, or may be determined by routine experimentation. used as a guideline for determining the amount of gabapentin, Such known or determined dosages of additional medica ora pharmaceutically acceptable salt thereof, to include in the ments may be used as a guideline for determining the amount lollipop, typically taking into account various patient charac of the additional medicament(s) to include in the lollipop, teristics (e.g., level of pain, age, Weight, and overall health) in typically taking into account various patient characteristics a manner known to those skilled in the medical arts, as well as (e.g., level of muscle tension, overexcitement, anxiety and/or the characteristics of the lollipop (e.g., rate of dissolution)and depression, age, weight, and overall health) in a manner the transmucosal delivery characteristics of the gabapentin, known to those skilled in the medical arts, as well as the or a pharmaceutically acceptable salt thereof. characteristics of the lollipop (e.g., rate of dissolution) and the 0022. For example, a preferred pain relief lollipop com transmucosal delivery characteristics of the particular medi prises a candy matrix comprising (a) an opioid agonist cament(s). selected from the group consisting of fentanyl, hydromor 0025 Pain relief lollipops are preferably made by inter phone, hydrocodone, oxycodone, oxymorphone, pro mixing the medicaments (e.g., opioid agonist, NMDA recep poxyphene, Sulfentanil, and pharmaceutically acceptable tor antagonist, gabapentin, or a pharmaceutically acceptable salts thereof, (b) an N-methyl-D-aspartate receptor antago salt thereof, and, optionally, muscle relaxant, sedative, anxi nist selected from the group consisting of amantadine, dex olytic and/or antidepressant) with the other non-medicinal tromethorphan, and pharmaceutically acceptable salts lollipop ingredients (e.g., candy, Sorbitol, flavoring, coloring, thereof (c) gabapentin, or a pharmaceutically acceptable salt etc.) during the making of the lollipops. The non-medicinal thereof, and a holder in contact with the candy matrix. lollipop ingredients are preferably selected to slowly dissolve 0023 Pain relief lollipops may optionally contain addi and/or melt in the patient's mouth in a manner similar to that tional medicaments to provide further comfort and/or relief to of a traditional lollipop, so as to release the medicaments over the patient, and/or to treat specific conditions such a muscle the course of dissolution and/or melting. The medicaments tension, overexcitement, anxiety and/or depression. Prefer may be incorporated into the lollipop in other ways, e.g. by ably, the lollipop candy further comprises a medicament coating onto the exterior of a lollipop, but incorporation dur selected from the group consisting of a muscle relaxant, a ing manufacture is generally preferable so that the medica sedative, an anxiolytic and an antidepressant, the medicament ments are more uniformly dispersed throughout the resulting being different from the opioid agonist and different from the candy matrix. Such relatively uniform dispersal has been N-methyl-D-aspartate receptor antagonist. The terms found to provide a corresponding uniform release and Subse “muscle relaxant,” “sedative.” “anxiolytic' and “antidepres quent transmucosal absorption of the medicaments during Sant' are known to those skilled in the art, see, e.g., Physi administration of the lollipop to the patient. cian's Desk Reference 2003 and Dorland's Illustrated Medi 0026 Methods for making conventional lollipops are well cal Dictionary, W.B. Saunders Co., 2000, and include known in the art. A preferred embodiment of the invention mixtures thereof. Non-limiting examples of preferred muscle provides a method for making a pain relief lollipop, compris relaxants include alprazolam, butalbital, clonazepam, cariso ing intermixing the various medicaments and non-medicinal prodol, diazepam, flexeril, lorazepam, methocarbamol, and ingredients in the molten or partially molten state by heating pharmaceutically acceptable salts thereof. Non-limiting the ingredients to a temperature effective to melt or partially examples of sedatives include clonazepam, butalbital, diaz melt at least part of the ingredients, preferably at a tempera epam, phenobarbital, and pharmaceutically acceptable salts ture in the range of about 35° C. to about 95°C., pouring the thereof. Non-limiting examples of anxiolytics include alpra resulting molten or partially molten lollipop mixture into a Zolam, clonazepam, diazepam, lorazepam, and pharmaceuti mold or molds, placing a stick, String or other Suitable object US 2009/019 1257 A1 Jul. 30, 2009

into the molded mixture so that part protrudes to serve as a phan, 0.35 g silica gel, and 1.3 g sodium saccharin are inter holder, and cooling the lollipop mixture to form a hardened or mixed and added to the mixture in the beaker with stirring. semi-hardened candy attached to the holder. In an alternative About 22.5g of gabapentin is weighed in the barrel of a 50 ml embodiment, the holder is placed in contact with, e.g., Syringe. Water is drawn into the Syringe and the resulting attached to, the hardened or semi-hardened candy after cool mixture is shaken to provide agabapentin Solution. The gaba ing. Various methods for making the lollipop may be prac pentin solution is added to the mixture in the beaker with ticed according to the knowledge of those skilled in the art, stirring. About 6 mL raspberry flavor and about 3.6 mL wild although extreme manufacturing conditions that significantly cherry oil are then added with stirring to the mixture in the alter the efficacy of the medicaments are to be avoided. beaker to form a lollipop solution. The lollipop solution is 0027. A preferred embodiment provides methods for then drawn into a 60 mL syringe, which is then used to fill treating pain, comprising identifying a human Suffering from each of the 216 suppository molds. One end of a 2-3 inch pain and administering a pain relief lollipop as described plastic stick is then placed near the center of each lollipop to herein to the human. Methods for identifying humans suffer form a handle. The lollipops in the mold are then refrigerated ing from pain and assessing the appropriate method of pro overnight then removed from the molds. Each of the resulting viding relief are known to those skilled in the medical arts. lollipops contains about 4 milligrams (mg) of hydromor Administration of the pain relief lollipop is preferably by phone, about 2 mg of dextromethorphan and about 100 mg of patient self-administration, e.g., by Sucking or licking the gabapentin. lollipop, such that oral transmucosal delivery of the various medicaments is facilitated. The pain relief lollipop may be EXAMPLE 2 chewed and swallowed to provide gastrointestinal delivery of the medicaments, but administration of the lollipop is prefer 0030 Eighteen suppository mold strips (each containing ably conducted by advising the patient not to chew or swallow 12 molds) in a metal-holding tray are set up on top of wax pieces of the lollipop in order to provide preferred oral trans paper in a vertical flow hood. The mold strips are sprayed with mucosal delivery. Other preferred embodiments comprise cooking oil spray and a rubber spatula was used across the identifying a patient Suffering from pain as well as muscle tops of the molds to push oil inside. A spin bar is placed into tension, overexcitement, anxiety and/or depression, and a 500 mL beaker and about 620 g of a commercially available administering a pain relief lollipop further comprising a sorbitol lollipop base is added to the beaker. The contents are muscle relaxant, sedative, anxiolytic and/orantidepressant, to heated on a hot plate at about 90°C. with magnetic stirring to treat Such muscle tension, overexcitement, anxiety and/or melt the lollipop base. About 0.50 g of fentanyl citrate is depression, respectively. weighed in the barrel of a 20 mL syringe. Water and red food 0028. The pain relief lollipops described herein are par coloring are drawn into the Syringe and the resulting mixture ticularly useful for the treatment of patients suffering from is shaken to provide a hydromorphone solution. The hydro chronic pain because Such treatment may involve multiple morphone solution is then injected into the melted lollipop administrations over an extended period of time. In Such base over the course of several minutes with stirring. A uni situations, the preferred pain relief lollipops described herein form red color indicates complete dispersion of the ingredi may be used to provide numerous benefits, including relief of ents. The temperature of the molten mixture is reduced to the primary pain by the opioid agonist and avoidance or about 50° C. A mixture of 0.55 g dextromethorphan, 0.35g reduction of the development of tolerance and/or dependence silica gel, and 1.3 g Sodium saccharin are intermixed and by the patient to the opioid agonist, further treatment of pain added to the mixture in the beaker with stirring. About 22.5g with gabapentin, or a pharmaceutically acceptable salt of gabapentin is weighed in the barrel of a 50 ml syringe. thereof, as well as treatment of other conditions which may be Water is drawn into the Syringe and the resulting mixture is present Such as muscle tension, overexcitement, anxiety and/ shaken to provide agabapentin Solution. The gabapentin solu or depression, by the administration of additional medica tion is added to the mixture in the beaker with stirring. About ments such as muscle relaxants, sedatives, anxiolytics and 6 mL raspberry flavor and about 3.6 mL wild cherry oil is then antidepressants, respectively. added with stirring to the mixture in the beaker to form a lollipop solution. The lollipop solution is then drawn into a 60 mL syringe, which is then used to fill each of the 216 Sup EXAMPLE1 pository molds. One end of a 2-3 inch plastic stick is then 0029. Eighteen suppository mold strips (each containing placed near the center of each lollipop to form a handle. The 12 molds) in a metal-holding tray are set up on top of wax lollipops in the mold are then refrigerated overnight then paper in a vertical flow hood. The mold strips are sprayed with removed from the molds. Each of the resulting lollipops con cooking oil spray and a rubber spatula is used across the tops tains about 1.25 mg offentanyl, about 2 mg of dextrometho of the molds to push oil inside. A spin bar is placed into a 500 rphan and about 100 mg of gabapentin. milliliters (mL) beaker and about 620 grams (g) of a commer cially available sorbitol lollipop base is added to the beaker. EXAMPLE 3 The contents are heated on a hot plate at about 70° C. with 0031. The procedure described in Example 2 is repeated magnetic stirring to melt the lollipop base. About 1.1 g of except that a smaller amount (0.42 g) of fentanyl citrate is hydromorphone is weighed in the barrel of a 20 mL syringe. used. Each of the resulting lollipops contains about one mg of Water and red food coloring are drawn into the syringe and the fentanyl, about 2 mg of dextromethorphan and about 100 mg resulting mixture is shaken to provide a hydromorphone solu of gabapentin. tion. The hydromorphone solution is then injected into the melted lollipop base over the course of several minutes with stirring. A uniform red color indicates complete dispersion of EXAMPLE 4 the ingredients. The temperature of the molten mixture is 0032. The procedure described in Example 2 is repeated reduced to about 50° C. A mixture of 0.55 g dextromethor except that a smaller amount (0.22 g) of fentanyl citrate is US 2009/019 1257 A1 Jul. 30, 2009

used. Each of the resulting lollipops contains about 500 10. The pain relief lollipop of claim 9 in which the anxi micrograms offentanyl, about 2 mg of dextromethorphanand olytic is selected from the group consisting of alprazolam, about 100 mg of gabapentin. clonazepam, diazepam, lorazepam, and pharmaceutically acceptable salts thereof. EXAMPLE 5 11. The pain relief lollipop of claim 4 in which the candy 0033. The procedure described in Example 2 is repeated matrix further comprises an antidepressant. except that 2.16 g of methocarbamol is added to the mixture 12. The pain relief lollipop of claim 11 in which the anti of 0.55 g dextromethorphan, 0.35 g silica gel, and 1.3 g depressant is a tricyclic antidepressant selected from the Sodium saccharin. Each of the resulting lollipops contains group consisting of amitriptyline, amoxapine, desipramine, about 1.25 mg offentanyl, 10 mg methocarbamol, about 2 mg doxepin, imipramine, maprotiline, nortriptyline, protrip of dextromethorphan, and about 100 mg of gabapentin. tyline, trimipramine, and pharmaceutically acceptable salts 0034. Although the foregoing invention has been thereof. described in terms of certain preferred embodiments, other 13. The pain relief lollipop of claim 4 in which the candy embodiments will become apparent to those of ordinary skill matrix further comprises at least two different medicaments in the art in view of the disclosure herein. Accordingly, the selected from the group consisting of a muscle relaxant, a invention is not intended to be limited by the recitation of sedative, an anxiolytic and a tricyclic antidepressant. preferred embodiments, but is intended to be defined solely 14. The pain relieflollipop of claim 13 in which the muscle by reference to the appended claims. relaxant is selected from the group consisting of alprazolam, What is claimed is: butalbital, clonazepam, diazepam, flexeril, lorazepam, 1. A pain relief lollipop, comprising: methocarbamol, and pharmaceutically acceptable salts a candy matrix comprising (a) an opioid agonist, (b) an thereof; in which the sedative is selected from the group N-methyl-D-aspartate receptor antagonist different consisting of clonazepam, butalbital, diazepam, phenobar from the opioid agonist, and (c) gabapentin or a phar bital, and pharmaceutically acceptable salts thereof; in which maceutically acceptable salt thereof, and the anxiolytic is selected from the group consisting of alpra a holder in contact with the candy matrix. Zolam, clonazepam, diazepam, lorazepam, and pharmaceuti 2. The pain relief lollipop of claim 1 in which the opioid cally acceptable salts thereof; and in which the tricyclic anti agonist is selected from the group consisting of fentanyl. depressant is selected from the group consisting of hydromorphone, hydrocodone, ketamine, methadone, oxyc amitriptyline, amoxapine, desipramine, doxepin, imi odone, Oxymorphone, propoxyphene, Sulfentanil, and phar pramine, maprotiline, nortriptyline, protriptyline, trimi maceutically acceptable salts thereof. pramine, and pharmaceutically acceptable salts thereof. 3. The pain relief lollipop of claim 1 in which the N-me 15. A method for treating pain, comprising identifying a thyl-D-aspartate receptor antagonist is selected from the human Suffering from pain and administering the pain relief group consisting of amantadine, D.L-2-amino-5-phosphono lollipop of claim 1 to the human. Valeric acid, dextromethorphan, ketamine, methadone, and 16. The method of claim 15, wherein the pain is chronic pharmaceutically acceptable salts thereof. pain. 4. The pain relief lollipop of claim 1, wherein: 17. A method for making the pain relief lollipop of claim 1, the opioid agonist is selected from the group consisting of comprising intermixing the opioid agonist, N-methyl-D-as fentanyl, hydromorphone, hydrocodone, oxycodone, partate receptor antagonist, gabapentin or a pharmaceutically oxymorphone, propoxyphene, Sulfentanil, and pharma acceptable salt thereof and candy matrix at a temperature ceutically acceptable salts thereof, and effective to at least partially melt the candy matrix to form an the N-methyl-D-aspartate receptor antagonist is selected at least partially molten lollipop mixture, molding the at least from the group consisting of amantadine, dextrometho partially molten lollipop mixture to form a molded lollipop rphan, and pharmaceutically acceptable salts thereof. mixture, contacting the molded lollipop mixture with a 5. The pain relief lollipop of claim 4 in which the candy holder, and cooling the molded lollipop mixture to form a matrix further comprises a muscle relaxant. pain relief lollipop. 6. The pain relief lollipop of claim 5 in which the muscle 18. A method for making the pain relief lollipop of claim 1, relaxant is selected from the group consisting of alprazolam, comprising intermixing the opioid agonist, N-methyl-D-as butalbital, clonazepam, carisoprodol, diazepam, flexeril, partate receptor antagonist, gabapentin or a pharmaceutically lorazepam, methocarbamol, and pharmaceutically accept acceptable salt thereof and candy matrix at a temperature able salts thereof. effective to at least partially melt the candy matrix to form an 7. The pain relief lollipop of claim 4 in which the candy at least partially molten lollipop mixture, molding the at least matrix further comprises a sedative. partially molten lollipop mixture to form a molded lollipop 8. The pain relief lollipop of claim 7 in which the sedative mixture, cooling the molded lollipop mixture to form an at is selected from the group consisting of clonazepam, butal least partially hardened candy, and contacting the at least bital, diazepam, phenobarbital, and pharmaceutically accept partially hardened candy with a holder to form a pain relief able salts thereof. lollipop. 9. The pain relief lollipop of claim 4 in which the candy matrix further comprises an anxiolytic.