Abstract:
A tablet, pill or capsule containing a material which produces sound waves when the tablet, pill or capsule is exposed to the gastrointestinal system. A two step method for oral drug compliance monitoring. The first step is to ingest a tablet, pill or capsule containing a material which produces sound waves when the tablet, pill or capsule is exposed to the gastrointestinal system of a person. The second step is to detect the sound waves produced when the tablet, pill or capsule is exposed to the gastrointestinal system to confirm that the person has ingested the tablet, pill or capsule.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims the benefit of U.S. Provisional Application No. 60/701,707, filed Jul. 22, 2005. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The instant invention relates to oral drug compliance monitoring, and, more particularly, to a means for the detection of a material formulated into a drug tablet, pill or capsule that generates sound waves when the material is exposed to the environment of the gastrointestinal system. 
         [0003]    Non-compliance of patients to drug regimens prescribed by their physicians results in increased cost of medical care, higher complication rates, as well as drug wastage. Non-compliance refers to the failure to take the prescribed dosage at the prescribed time which results in under medication or overmedication. In a survey of 57 non-compliance studies, non-compliance ranged from 15% to as high as 95% in all study populations, regardless of medications, patient population characteristics, drug being delivered or study methodology [Greenberg R N: Overview of patient compliance with medication dosing: A literature review. Clinical Therapeutics, 6(5):592-599, 1984]. 
         [0004]    In the clinical drug stage, accurately measuring compliance can lead to benefits such as: improved statistical reliability of a clinical study; clinical studies being completed sooner; and a determination of the effect of non-compliance as a function of the degree of non-compliance. In the therapeutic stage, accurately measuring compliance has a number of important benefits such as: warning a patient about the potential for developing a drug resistant infection related to poor compliance; and identifying a side effect of a drug related to overdosing. 
         [0005]    Confirmation of drug compliance by way of direct observation by trained persons is effective but impractical in most situations. Confirmation of drug compliance by blood or urine analysis is also impractical in most situations. Transdermal detection devices attached to the skin of a patient have been developed which detect ingested drug components through the skin and such devices can transmit a signal to a remote receiver at an external site such as a healthcare facility, see U.S. Pat. No. 6,663,846 and USPAP 2005/0031536. Electronic sensor systems have been developed which detect ingested drug components in the breath of a patient, see USPAP 2004/0081587. Radio frequency identification (RFID) tags have been incorporated into drug pills, each tag capable of identifying the type of medication, its dosage, and its lot number by way of a unique code emitted by the tag when interrogated by a corresponding radio frequency “reader”, see U.S. Pat. No. 6,366,206. 
         [0006]    Despite the many advances made in the prior art, it would be an advance in the art of drug compliance if a less complicated means could be discovered to determine drug compliance. 
       SUMMARY OF THE INVENTION 
       [0007]    The instant invention is a solution to the above stated problem. More specifically, the instant invention is an oral drug delivery system, comprising: a tablet, pill or capsule comprising sound generation means that produce sound waves when the tablet, pill or capsule is exposed to the gastrointestinal system. In another embodiment, the instant invention is a method for oral drug compliance monitoring, comprising the steps of: (a) ingesting a tablet, pill or capsule comprising a material which produces sound waves when the tablet, pill or capsule is exposed to the gastrointestinal system of a person; and (b) detecting the sound waves produced when the tablet, pill or capsule is exposed to the gastrointestinal system to confirm that the person has ingested the tablet, pill or capsule. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0008]      FIG. 1  is a cross-sectional side view of a pill or tablet containing granules of gasified candy; 
           [0009]      FIG. 2  is a cross-sectional side view of a pill or tablet coated with a highly crystalline fractureable water permeable material; 
           [0010]      FIG. 3  is a cross-sectional side view of a drug capsule containing granules of gasified candy; 
           [0011]      FIG. 4  is a cross-sectional side view of a capsule containing a drug formulation, the capsule made from a highly crystalline fractureable water permeable material; 
           [0012]      FIG. 5  is a schematic drawing of a sound sensor system; 
           [0013]      FIG. 6  is a perspective view of a bag containing a sound sensor system adapted to be worn around the waist of a person; 
           [0014]      FIG. 7  is a perspective view of a watch-like container containing a sound sensor system adapted to be worn around the wrist of a person; and 
           [0015]      FIG. 8  is a perspective view of a pendent-like container containing a sound sensor system adapted to be worn around the neck of a person. 
       
    
    
     DETAILED DESCRIPTION 
       [0016]    The drug delivery system of the present invention comprises a tablet, pill or capsule comprising sound generation means that produce sound waves when the tablet, pill or capsule is exposed to the gastrointestinal system. Sound generation means include, for example, a material having properties that generate sound waves when exposed to water. Sound generation means also include a device capable of generating sound waves through electronic, hydraulic, or mechanical means. Examples of devices utilizing electronic means to generate sound waves include piezoelectric ultrasound generating devices commonly available, voice coil systems, speakers, and electric current systems. Examples of devices utilizing hydraulic means to generate sound waves include fluidic oscillators and similar devices such as a whistle. Examples of devices utilizing mechanical means to generate sound waves include hammer-like devices, tuning forks, and other devices utilizing a mechanism to hit a resonant object. Optimally, the sound generation means is capable of modulating the sound waves generated for the purposes of transmitting a serial number or a unique identifying signal associated with the specific pill, tablet, or capsule. 
         [0017]    Referring now to  FIG. 1 , therein is shown a cross-sectional side view of a pill or tablet  10 . The pill or tablet  10  comprises sound generation means such as, in the embodiment shown, a material that is granules of gasified candy  12 . Optionally, the pill or tablet  10  comprises a drug formulation  11 . When the pill or tablet  10  is ingested, it disperses in the gastrointestinal syslem and exposes the gasified candy  12  to water thereby releasing the gas trapped in the gasified candy to produce sound waves. 
         [0018]    Gasified candy is commercially available under the trade name POP ROCKS. U.S. Pat. No. 4,289,794 (herein fully incorporated by reference) teaches a preferred method for preparing gasified candy. 
         [0019]    Referring now to  FIG. 2 , therein is shown a cross-sectional side view of a pill or tablet  13 . The pill or tablet  13  is coated with a highly crystalline fractureable water permeable material  14  and optionally comprises a drug formulation  15 . When the pill or tablet  13  is ingested, water permeates into the pill or tablet  13  and eventually the highly crystalline fractureable water permeable material  14  fractures to produce sound waves. 
         [0020]    Highly crystalline fractureable water permeable material can be selected from appropriate grades of one or more of the following materials: ethyl cellulose, cellulose acetate and polylactidefglycolide copolymer. Referring now to  FIG. 3 , therein is shown a cross-sectional side view of a drug capsule  16 . The drug capsule  16  contains granules of gasified candy  20  contained in gelatin capsule portions  17  and  18  and optionally contains a drug formulation  19 . When the capsule  16  is ingested, it disperses in the gastrointestinal system and exposes the gasified candy  20  to water thereby releasing the gas trapped in the gasified candy to produce sound waves. 
         [0021]    Referring now to  FIG. 4 , therein is shown a cross-sectional side view of a drug capsule  21 . The drug capsule  21  comprises capsule portions  22  and  23 . Capsule portions  22  and  23  are made of a highly crystalline fractureable water permeable material and optionally contain a drug formulation  24 . When the capsule  21  is ingested, the capsule portions  22  and  23  are exposed to water. The water permeates into the capsule  21  eventually fracturing the highly crystalline fractureable water dispersible material to produce sound waves. 
         [0022]    Referring now to  FIG. 5 , therein is shown a highly preferred sound sensor system  25  including a 9000 series piezo microphone  26  from Senscomp (Livonia, Mich.). One lead from the microphone  26  is grounded while the other lead is connected to a 10 M ohm resistor  27  and an MMBT5089 transistor  28 . The resistor  27  and transistor  28  are connected to a 15 K ohm resistor  29  and a MMBT5087 transistor  30 . A 5 volt direct current power source  33  is connected to a 10 K ohm resistor  32  which is connected to a 0.1 microfarad capacitor  34  and a 27 K ohm resistor  31 . The resistor  29 , the transistor  30  and the resistor  31  are connected to a 150 Pico Farad capacitor  35 . A 2.5 volt direct current power source  37  is connected to the other lead of the capacitor  35  and to an operational amplifier  38  having a gain of 100. The output of the operational amplifier is passed through a 40 to 60 kilohertz band pass filter  39 , through a level detector  40  and then to a microprocessor/data logger  41 . The microprocessor/data logger  41  can be connected to (or communicate in a wireless manner) with a digital computer  42  for drug compliance monitoring at the patients residence and/or a health care facility. 
         [0023]    The band pass filter  39  is highly preferred to filter out interfering sounds at lower frequencies that can come from the gastrointestinal system. The level detector  40  is highly preferred to filter out ultrasonic signals of a level too low to be caused by the fracturing of highly crystalline fractureable water permeable material or the sudden gas release of the gasified candy in the gastrointestinal system. Optimally, the sound sensor is capable of demodulating the sound waves and recovering a transmitted serial number or other unique identifying signal associated with the specific pill, tablet or capsule. 
         [0024]    Referring now to  FIG. 6 , therein is shown a perspective view of a pack system  43  comprised of a belt  45  and a bag  44  containing the sound sensor system  25  of  FIG. 5 . The pack system  43  is adapted to be worn around the waist of a person. The pack system  43  is highly preferred because it places the microphone of the sound sensor system in relatively close proximity to the gastrointestinal system of the person wearing the pack system  43 . 
         [0025]    Referring now to  FIG. 7 , therein is shown a perspective view of a case system  46  comprised of a strap  48  and a case  47  containing the sound sensor system  25  of  FIG. 5 . The case system  46  is adapted to be worn around the wrist of a person. The case system  46  is convenient to wear but places the microphone of the sound sensor system relatively far from the gastrointestinal system of the person wearing the case system  46 . 
         [0026]    Referring now to  FIG. 8 , therein is shown a perspective view of a pendent system  49  comprised of a cord  51  and a pendent compartment  50  containing the sound sensor system  25  of  FIG. 5 . The pendent system  49  is adapted to be worn around the neck of a person. The pendent system  43  is more preferred than the case system  46  of  FIG. 7  because it places the microphone of the sound sensor system in closer proximity to the gastrointestinal system of the person wearing the pendent system  49 . 
         [0027]    While the instant invention has been described above according to its preferred embodiments, it can be modified within the spirit and scope of this disclosure. For example, the case  47  of  FIG. 7  could be adhesively attached to a convenient location on a patient&#39;s abdomen. This application is therefore intended to cover any variations, uses, or adaptations of the instant invention using the general principles disclosed herein. Further, the instant application is intended to cover such departures from the present disclosure as come within the known or customary practice in the art to which this invention pertains and which fall within the limits of the following claims.