Abstract:
Technologies are described for formulations and methods to produce sublingual antidepressant lozenges. The lozenges may comprise troche base and ketamine. The lozenges may comprise 0.35 weight percent to 0.65 weight percent ketamine. The methods may comprise placing troche base into a chamber. The methods may comprise applying heat to the chamber. The heat may be sufficient to melt the troche base in the chamber. The methods may comprise adding a first ingredient into the chamber. The first ingredient may include ketamine. The methods may comprise mixing the first ingredient into the melted troche base in the chamber to form a melted mixture. The methods may comprise pouring the melted mixture into a mold. The methods may comprise cooling the melted mixture in the mold to form the lozenge.

Description:
BACKGROUND 
       [0001]    Antidepressant treatments may include therapies that target monoaminergic (MA) systems. Antidepressant treatments that target monoaminergic (MA) systems may require 4-6 weeks of administration to achieve effects, may include unpleasant side effects, may possess modest efficacy rates, and may display significant relapse rates. N-Methyl-D-aspartate (NMDA) receptor antagonists may be used as anesthetics and hallucinogenic recreational drugs. Ketamine, diethyl ether, dizocilpine, memantine, phencyclidine, nitrous oxide, and dextromethorphan may be MNDA receptor antagonists. 
       SUMMARY 
       [0002]    In some examples lozenges are described. The lozenges may comprise troche base and ketamine. The lozenges may comprise 0.35 weight percent to 0.65 weight percent ketamine. 
         [0003]    In some examples, methods to produce lozenges are described. The methods may comprise placing troche base into a chamber. The methods may comprise applying heat to the chamber. The heat may be sufficient to melt the troche base in the chamber. The methods may comprise adding a first ingredient into the chamber. The first ingredient may include ketamine. The methods may comprise mixing the first ingredient into the melted troche base in the chamber to form a melted mixture. The methods may comprise pouring the melted mixture into a mold. The methods may comprise cooling the melted mixture in the mold to form the lozenge. 
         [0004]    In some examples lozenges are described. The lozenges may comprise troche base and ketamine. The lozenges may comprise 0.995 grams of troche base and 0.005 grams of ketamine. 
         [0005]    The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0006]    The foregoing and other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which: 
           [0007]      FIG. 1  illustrates an example system that can be utilized to produce a sublingual antidepressant lozenge; 
           [0008]      FIG. 2  illustrates a flow diagram of an example process to produce a sublingual antidepressant lozenge; 
       
    
    
       [0009]    all arranged according to at least some embodiments described herein. 
       DETAILED DESCRIPTION 
       [0010]    In the following detailed description, reference is made to the accompanying drawings, which form a part hereof In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein. 
         [0011]    It will be understood that any compound, material or substance which is expressly or implicitly disclosed in the specification and/or recited in a claim as belonging to a group or structurally, compositionally and/or functionally related compounds, materials or substances, includes individual representatives of the group and all combinations thereof. 
         [0012]      FIG. 1  illustrates an example system that can be utilized to produce a sublingual antidepressant lozenge, arranged in accordance with at least some embodiments presented herein. As discussed in more detail below, a sublingual antidepressant lozenge may be effective in the treatment of depression and anxiety. 
         [0013]    System  100  may include a chamber  20 , a heater  30  and a lozenge mold  90 . At  102  a troche base  10  may be placed in within chamber  20  and melted by heat from heater  30  to produce melted troche base  15 . Troche base  10  may be a blend of polyethylene glycols (PEGs). Troche base  10  may be white and/or translucent in appearance and be in the shape of small pellet pieces. Troche base  10  may be solid at room temperatures of 20 to 25 degrees Celsius. Heater  30  may supply heat to increase a temperature of troche base  10  to about 45 to 60 degrees Celsius and melt troche base  10  to produce melted troche base  15 . 
         [0014]    At  104 , a mixing instrument  25  may be inserted into chamber  20  and ingredients  40 ,  50 ,  60   70 , and  80  may each be individually and respectively added and blended into melted troche base  15 . Mixing instrument  25  may be a manual mixing instrument such as a spoon or whisk, or an automated mixer. 
         [0015]    Ingredient  40  may be in powder form. Ingredient  40  may include ketamine. Ingredient  40  may include ketamine hydrochloride (HCl) powder. 
         [0016]    Ingredient  50  may be in powder form. Ingredient  50  may include silica gel powder. Ingredient  50  may be granular, vitreous in appearance, and porous. Ingredient  50  may be tough and hard in texture. Ingredient  50  may include a strong affinity for water molecules. Ingredient  50  may be silicon dioxide produced synthetically from sodium silicate. Ingredient  50  may have an average pore size of about 2.4 nanometers. Ingredient  50  may be a suspending agent and may keep materials from settling at the bottom of a mold cavity during cooling. 
         [0017]    Ingredient  60  may be in powder form. Ingredient  60  may include a weak organic tribasic acid. Ingredient  60  may include citrate. Ingredient  60  may include citric acid powder. Ingredient  60  may include an acidifier, a flavoring, a chelating agent, or a pH adjusting agent. Ingredient  60  may include a processing aid. 
         [0018]    Ingredient  70  may be in powder form. Ingredient  70  may include acacia powder. Ingredient  70  may include gum exuded from the acacia tree. Ingredient  70  may include dietary fiber that can dissolve in water. Ingredient  70  may add texture and smoothness to a sublingual antidepressant lozenge. 
         [0019]    Ingredient  80  may be in liquid form. Ingredient  80  may be a liquid flavoring. Ingredient  80  may include a liquid confection product. Ingredient  80  may enhance digestion and taste of a sublingual antidepressant lozenge. 
         [0020]    As shown at  104 , ingredient  40  may be added to chamber  20  and blended into melted troche base  15 . Ingredient  40  may be geometrically diluted into melted troche base  15 . Ingredient  40  may be mixed until ingredient  40  is evenly distributed throughout melted troche base  15  as indicated by an even distribution of a color of ingredient  40  throughout melted troche base  15 . 
         [0021]    As shown at  104 , ingredient  50  may be added to chamber  20  and blended into melted troche base  15 . Ingredient  50  may be geometrically diluted into melted troche base  15 . Ingredient  50  may be mixed until ingredient  50  is evenly distributed throughout melted troche base  15  as indicated by an even distribution of a color of ingredient  50  throughout melted troche base  15 . 
         [0022]    As shown at  104 , ingredient  60  may be added to chamber  20  and blended into melted troche base  15 . Ingredient  60  may be geometrically diluted into melted troche base  15 . Ingredient  60  may be mixed until ingredient  60  is evenly distributed throughout melted troche base  15  as indicated by an even distribution of a color of ingredient  60  throughout melted troche base  15 . 
         [0023]    As shown at  104 , ingredient  70  may be added to chamber  20  and blended into melted troche base  15 . Ingredient  70  may be geometrically diluted into melted troche base  15 . Ingredient  70  may be mixed until ingredient  70  is evenly distributed throughout melted troche base  15  as indicated by an even distribution of a color of ingredient  70  throughout melted troche base  15 . 
         [0024]    As shown at  104 , ingredient  80  may be added to chamber  20  and blended into melted troche base  15 . Ingredient  80  may be mixed until ingredient  80  is evenly distributed throughout melted troche base  15  as indicated by an even distribution of a color of ingredient  80  throughout melted troche base  15 . 
         [0025]    A melted lozenge mixture  85  may be formed by mixing ingredients  40 ,  50 ,  60   70 , and  80  into melted troche base  15 . Melted lozenge mixture  85  may be poured into cavities  120  of lozenge mold  90 . Lozenge mold  90  may be plastic, anodized aluminum, or some other non-permeable material, and may be configured to form equal sized lozenges. Lozenge mold  90  may include  30  uniformly sized cavities  120 . Melted lozenge mixture  85  may be poured into cavities  120  of lozenge mold  90  so as to completely fill cavities  120 . A scrapper or spatula  110  may be used to level and even out poured melted lozenge mixture  85  in cavities  120  of lozenge mold  90 . Spatula  110  may also be used to wipe any excess melted lozenge mixture  85  off of lozenge mold  90 . 
         [0026]    Lozenge mold  90 , with cavities  120  filled with melted lozenge mixture  85 , may be cooled to room temperature of 20 to 25 degrees Celsius to form lozenge  130 . Lozenge  130  may be a solid lozenge with ingredients  40 ,  50 ,  60 ,  70 , and  80  distributed evenly throughout lozenge  130 . Lozenge  130  may include about 0.35 weight percent to about 0.65 weight percent of ingredient  40 . Lozenge  130  may include about 1.05 weight percent to about 1.35 weight percent of ingredient  50 . Lozenge  130  may include about 1.20 weight percent to about 1.55 weight percent of ingredient  60 . Lozenge  130  may include about 1.80 weight percent to about 2.10 weight percent of ingredient  70 . 
       EXAMPLE 1 
       [0027]    Lozenge  130  may include: 
         [0000]    
       
         
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 0.5 weight percent of ingredient 40; 
               
               
                   
                 1.2 weight percent of ingredient 50; 
               
               
                   
                 1.38 weight percent of ingredient 60; and 
               
               
                   
                 1.98 weight percent of ingredient 70. 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 2 
       [0028]    A mold with 30 uniformly sized cavities may be utilized to mold 30 lozenges  130  from melted lozenge mixture  85  formed from the following quantities: 
         [0000]                                0.150 grams of ingredient 40. Ingredient 40 may be ketamine HCl powder.       0.360 grams of ingredient 50. Ingredient 50 may be silica gel powder.       0.414 grams of ingredient 60. Ingredient 60 may be citric acid powder.       0.594 grams of ingredient 70. Ingredient 70 may be  acacia  powder.       29.850 grams of troche base 10.                    
6.000 ml of ingredient  80 . Ingredient  80  may be tutti frutti flavor liquid.
 
       EXAMPLE 3 
       [0029]    Lozenge  130  may be formed from the following quantities: 
         [0000]    
       
         
               
             
           
               
                   
               
             
             
               
                 0.005 grams of ingredient 40. Ingredient 40 may be ketamine HCl powder. 
               
               
                 0.012 grams of ingredient 50. Ingredient 50 may be silica gel powder. 
               
               
                 0.0138 grams of ingredient 60. Ingredient 60 may be citric acid powder. 
               
               
                 0.0198 grams of ingredient 70. Ingredient 70 may be  acacia  powder. 
               
               
                 0.995 grams of troche base 10. 
               
               
                 0.200 ml of ingredient 80. Ingredient 80 may be tutti frutti flavor liquid. 
               
               
                   
               
             
          
         
       
     
         [0030]      FIG. 2  illustrates a flow diagram of an example process to produce a sublingual antidepressant lozenge  130 . The process in  FIG. 2  could be implemented using, for example, system  100  discussed above. An example process may include one or more operations, actions, or functions as illustrated by one or more of blocks S 2 , S 4 , S 6 , S 8 , and/or S 10 . Although illustrated as discrete blocks, various blocks may be divided into additional blocks, combined into fewer blocks, or eliminated, depending on the desired implementation. 
         [0031]    Processing may begin at block S 2 , “Place troche base into a chamber.” At block S 2 , a troche base may be placed into a chamber. The troche base may be a blend of polyethylene glycols (PEGs). The troche base may be white and/or translucent in appearance and be in the shape of small pellet pieces. The troche base may be solid at room temperatures of 20 to 25 degrees Celsius. 
         [0032]    Processing may continue from block S 2  to block S 4 , “Apply heat to the chamber sufficient to melt the troche base in the chamber.” At block S 4 , heat may be applied to the chamber sufficient to melt the troche base. Heat may be applied to the chamber sufficient to increase a temperature of the troche base to about 45 to 60 degrees Celsius and melt the troche base. 
         [0033]    Processing may continue from block S 4  to block S 6 , “Add a first ingredient into the chamber, wherein the first ingredient includes ketamine.” At block S 6 , a first ingredient may be added to the chamber. The first ingredient may include ketamine. The first ingredient may include ketamine hydrochloride (HCl) powder. 
         [0034]    Processing may continue from block S 6  to block S 8 , “Mix the first ingredient into the melted troche base in the chamber to form a melted mixture.” At block S 8 , the first ingredient may be mixed into the melted troche base in the chamber. The mixing may be performed by a manual mixing instrument such as a spoon or whisk, or an automated mixer. The first ingredient may be mixed until the first ingredient is evenly distributed throughout the melted troche base as indicated by an even distribution of a color of the first ingredient throughout the melted troche base. 
         [0035]    Processing may continue from block S 8  to block S 10 , “Pour the melted mixture into a mold.” At block S 10 , the melted mixture may be poured into a mold. The mold may be plastic, anodized aluminum, or some other non-permeable material. The mold may be configured with cavities to form uniform sized lozenges. The melted mixture may be poured into the cavities of the mold. The melted mixture may be poured into the cavities of the mold so as to completely fill the cavities of the mold. A scrapper or spatula may be used to level and even out poured melted mixture in the cavities of the mold. The spatula may also be used to wipe any excess melted mixture off of the mold. 
         [0036]    Processing may continue from block S 10  to block S 12 , “Cool the melted mixture in the mold to form the lozenge.” At block S 12 , the melted mixture in the mold may be cooled to form the lozenge. The melted mixture may be cooled to room temperature of 20 to 25 degrees Celsius. 
         [0037]    A system in accordance with the present disclosure may be effective to produce a sublingual antidepressant lozenge. A potential benefit of the present application may be the treatment of depression effects in treatment-resistant depression. An embodiment of the present application may provide a more rapid effect than antidepressant treatments which include therapies that target monoaminergic (MA) systems and require 4-6 weeks of administration to achieve effects. An embodiment of the present application may provide a higher efficacy rate than therapies that target monoaminergic (MA) systems. 
         [0038]    While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.