Aerosolizable gel

Abstract

There is provided an aerosolizable gel comprising (a) an active agent; (b) one or more gel forming materials, wherein the one or more gel forming material is at least one phyllosilicate; (c) an aerosol forming material selected from glycerol, propylene glycol and mixtures thereof; and (d) water.

Claims

1. A dosage form of an aerosolizable product, wherein the dosage form of the aerosolizable gel comprises: (a) nicotine in an amount of 0.5 to 10 mg; (b) one or more gel forming materials, wherein the one or more gel forming materials is at least kaolinite; (c) an aerosol forming material; and (d) water.

2. An aerosolizable gel according to claim 1 wherein the nicotine is present in an amount of no greater than 2 wt % based on the total weight of the aerosolizable gel.

3. An aerosolizable gel according to claim 1 wherein the nicotine is present in an amount of no greater than 1.8 wt % based on the total weight of the aerosolizable gel.

4. An aerosolizable gel according to claim 1 wherein the kaolinite is present in an amount of 10 to 80 wt. % based on the aerosolizable gel.

5. An aerosolizable gel according to claim 1 wherein the kaolinite is present in an amount of 20 to 70 wt. % based on the aerosolizable gel.

6. An aerosolizable gel according to claim 1 wherein the kaolinite is present in an amount of 30 to 60 wt. % based on the aerosolizable gel.

7. An aerosolizable gel according to claim 1 wherein the aerosol forming material is selected from glycerol, propylene glycol and mixtures thereof.

8. An aerosolizable gel according to claim 1 wherein the aerosol forming material is a combination of glycerol and propylene glycol.

9. An aerosolizable gel according to claim 1 wherein the aerosol forming material is present in an amount of 10 to 60 wt. % based on the aerosolizable gel.

10. An aerosolizable gel according to claim 1 wherein the aerosol forming material is present in an amount of 20 to 40 wt. % based on the aerosolizable gel.

11. An aerosolizable gel according to claim 1 wherein the water is present in an amount of 1 to 40 wt. % based on the aerosolizable gel.

12. An aerosolizable gel according to claim 1 wherein the water is present in an amount of 1 to 20 wt. % based on the aerosolizable gel.

13. A method of forming an aerosol, the method comprising the step of heating an aerosolizable gel comprising; (a) an active agent; (b) a gel forming material, wherein the gel forming material is at least kaolinite; (c) an aerosol forming material; and (d) water.

14. A method of forming an aerosol according to claim 13 wherein the aerosol forming material is selected from glycerol, propylene glycol and mixtures thereof.

15. A method of forming an aerosol according to claim 13 wherein the aerosolizable gel is an aerosolizable gel comprises: nicotine in an amount of no greater than 2 wt % based on the total weight of the aerosolizable gel; kaolinite in an amount of 10 to 80 wt. % based on the aerosolizable gel; the aerosol forming material is present in an amount of 10 to 60 wt. % based on the aerosolizable gel; and water present in an amount of 1 to 20 wt. % based on the aerosolizable gel.

16. An electronic vapour provision system comprising: (i) an aerosolizable gel comprising (a) an active agent; (b) one or more gel forming materials, wherein the one or more gel forming material is at least kaolinite; (c) an aerosol forming material; and (d) water; (ii) a heater for heating the aerosolizable gel and thereby vaporising some or all of the aerosolizable gel for inhalation by a user of the electronic vapour provision system.

17. A method of forming an aerosol according to claim 16 wherein the aerosolizable gel is an aerosolizable gel comprising: nicotine in an amount of no greater than 2 wt % based on the total weight of the aerosolizable gel; kaolinite in an amount of 10 to 80 wt. % based on the aerosolizable gel; the aerosol forming material is present in an amount of 10 to 60 wt. % based on the aerosolizable gel; and water present in an amount of 1 to 20 wt. % based on the aerosolizable gel.

18. The method of claim 13, wherein the aerosol forming material is a combination of glycerol and propylene glycol.

19. The method of claim 16, wherein the aerosol forming material is a combination of glycerol and propylene glycol.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The present invention will now be described in further detail by way of example only with reference to the accompanying figure in which:

(2) FIG. 1: Gels are composed of gel forming scaffolds holding onto a base e-liquid.

(3) FIG. 2a: SEM micrograph of kaolin clay (Barrisurf XD)

(4) FIG. 2b: Gels made with kaolin clay loading levels between 30% and 60%

(5) FIG. 3: Calculated energy of vaporization for the e-liquid and 55% kaolin gel. The total energy includes heat capacity contributions from each element of the gel as well as latent heat of evaporation contributions for the e-liquid components.

(6) FIG. 4a: Evaporation rate data for various gels. Initial mass loss vs. time collected on a 10 puff equivalent samples on a 250° C. hot plate.

(7) FIG. 4b: Zoom of shaded are from FIG. 4a (first 200 seconds).

(8) FIG. 4c: Time required to evaporate 99% of the e-liquid for various gels. Data collected using the rapid heating apparatus.

(9) FIG. 4d: Current-voltage energy consumed while heating samples from FIG. 4a.

(10) FIG. 5: Aerosol generation/collection apparatus.

(11) FIG. 6: Aerosol composition.

(12) FIG. 7: Thermogravimetric analysis data for kaolinite gel product.

(13) The invention will now be described with reference to the following non-limiting example.

EXAMPLES

(14) Formulations

(15) Base e-liquid:

(16) Propylene glycol 25 wt. %

(17) Water 25 wt. %

(18) Nicotine 1.86 wt. %

(19) Glycerol 48.14 wt. %

(20) Kaolinite—Barrisurf XD available from Imerys

(21) For 10 g batch of 60% Kaolinite gel, mix 6 g Kaolinite with 4 g e-liquid

(22) The formulations described herein provided a gelled product comprising propylene glycol, nicotine, glycerol and water held together with a gel scaffold in the manner shown in FIG. 1.

(23) Kaolin clay is an aluminosilicate (Al.sub.2Si.sub.2O.sub.5(OH).sub.4) consisting of stacked platelets (FIG. 2a). We used Barrisurf HX, a kaolin supplied as a powder from Imerys with a shape factor of ˜100. The kaolin powder was combined as-supplied with the e-liquid and manually stirred until the mixture was homogeneous. FIG. 2b shows the consistency of the mixtures with kaolin loading levels from 30% to 60%. Over this range, the mixture takes on a consistency ranging from thick liquid to a modeling clay-like putty. Like many clay-based pastes, these gels have a shear thinning rheology.

(24) Testing Results:

(25) Energy of Vaporization

(26) For formulations with significant loading levels of additives, the added thermal mass of the additives should be considered. A crude estimate of the energy required to vaporize each formulation can be made by adding up the energy required to heat each component to its boiling point and the latent heat for each component to be vaporized. The contribution from each component is shown in FIG. 3 for the e-liquid as well as kaolin gels Despite only comprising 25% of the formulation, the water accounts for a significant portion of the energy require to vaporize the e-liquid.

(27) Table: Energy required to evaporate various gel from heat flow data obtained using differential scanning calorimetry. The total energy was calculated by integrated the heat flow data from 25° C. to 300° C.

(28) TABLE-US-00001 ΔH (kJ/g) E-liquid 1.39 55% Kaolin 1.90

(29) Experimentally the energy required to vaporize the gels were measured by differential scanning calorimetry. The above Table shows the integrated heat flow in the heating range from 25° C. to 300° C. This measurement confirms that the added contribution to the energy required to vaporize from significant levels of kaolinite is minor.

(30) Evaporation Kinetics:

(31) The evaporation rate of the gels was determined gravimetrically by measuring the mass loss as a function of heating time. Initial measurements were performed by heating gel samples on hot plate—later, this was replaced by faster heating aerosol test rig. Sample sizes were chosen such that samples from the different formulations each contain the same mass of e-liquid (5-10 puff equivalents).

(32) FIG. 4a shows the mass loss vs time for kaolinite gel. These measurements were performed on a 10 puff equivalent (containing ˜1 mg nicotine) and were heated on a 250° C. hotplate. On this time-scale, the kaolinite gel exhibited similar heating profiles compared to the raw e-liquid.

(33) Aerosol test rig: In order to heat the gels on a time-scale closer to that of an e-cigarette device, we constructed a test rig for rapidly heating the gel and collecting the aerosol (FIG. 5). All subsequent evaporation rate measurements were performed on this device. The heating element (a ceramic disc resistive element) was used to heat samples in a 25 mg aluminum pan. A set-point of 300° C. can be reached within ˜3-5 seconds. The heater sits in a glass chamber which is used to collect the aerosol onto a glass filter.

(34) FIG. 4c shows the heating time and energy required to aerosolize 55% kaolinite gel. The sample (5 puff equivalent) was heated to 300° C. and held for set durations. The change in sample mass was measured to determine the time required to vaporize 99% of the e-liquid in the sample. In addition to this gravimetric analysis, we also monitored power consumption to vaporize the sample and compared it to the energy required to heat the aluminum pan alone for that duration (FIG. 4d).

(35) Aerosol Extraction and GC/MS Analysis:

(36) The composition of the aerosols generated from the five puff gel equivalents were analyzed by gas chromatography-mass spectrometry (GC/MS). The aerosol generated on the heating apparatus was collected onto a glass filter pad by evacuating the chamber with a vacuum pump. Deposits on the filter pad and on the chamber walls were extracted in methanol and analyzed.

(37) The aerosol was collected by placing an inverted Sterlitech glass filtration apparatus (Cat. #311420) over the heater, with a Whatman 47 mm glass microfiber filter pad (Cat. #1821-047) attached to the apparatus to collect the aerosol. The filtration apparatus was connected to an Airpo pump (model #D2028B), with a maximum pump-rate of 12-15 LPM. The pump was set to begin running upon initiation of heating and to continue running for at least 10 seconds after the sample e-liquid was completely aerosolized. The filter was then placed in 10 mL of anhydrous methanol (Sigma-Aldrich Cat. #322415) in a 100 mL glass jar. The aerosol was extracted from the filter pad by gentle shaking of the jar for 30-60 sec. After initial extraction, the filter pad was removed from the methanol extraction solvent, squeezed to remove excess methanol and used to wipe the area around the sample holder pan and the exposed surfaces of the heating rig. The filter was then placed back in the methanol solvent to extract for another 30-60 sec, then removed from methanol, squeezed dry and used to wipe any remaining aerosol residue from the inside of the glass filtration apparatus. The filter pad was then placed back into the methanol solvent for a final 1-2 min of extraction, after which it was removed from the solvent, squeezed dry one final time and discarded. The methanol with the extracted aerosol was transferred into a 1 mL GC/MS vial with a rubber-septum cap and analyzed using an auto-liquid sampler attached to the Agilent 7820A GC with 5977E MSD. The GC/MS procedure used a DB-WAX GC column (30 m length, 0.25 mm diameter, 0.25 μm film thickness, Cat. #122-7032) for analyte separation. The procedure was optimized to resolve the peaks corresponding to: propylene glycol, nicotine and glycerol. The GC procedure is as follows:

(38) TABLE-US-00002 Parameter Value Oven: Initial Temp.  50° C. Rate 30° C./min Final Temp. 260° C. Final Hold Time 2 min Inlet: Temp. 300° C. Mode Split Split Ratio 10:01 Split Flow Rate 20 mL/min Pressure 16.9 psi Column: Model # 122-7032 Description DB-WAX Max Temp. 260° C. Length 30 m Diameter 0.25 mm Film Thickness 0.25 gm Mode Constant Flow Flow Rate 2 mL/min Average Velocity 51.5 cm/sec

(39) To quantify the relative ratios of the e-liquid components, the peak areas from aerosol extraction results were compared to peak areas of a set of standards. The standards used to produce a calibration curve were made by diluting pure e-liquid in anhydrous methanol. The e-liquid was first diluted 100-fold by pipetting 100 uL of e-liquid into 9.9 mL of anhydrous methanol using micropipettes. The standards were then further diluted and labeled according to their nicotine content. The stock 1:100 dilution contained 1860 ppm nicotine and was used to make standards containing 10, 20, 30, 40 & 50 ppm nicotine. The anhydrous methanol was run as a blank, followed by the calibration curve standards. A fresh set of standards was made and analyzed for each series of extraction samples to ensure accurate calibration.

(40) We found it challenging to quantify the water content of the aerosol due to varying amounts absorbed during the aerosol collection. The water absorption could not be accounted for by running a blank filter through the extraction process. We, therefore, focused on quantifying the relative compositions of the remaining three components of the aerosol. The results are presented in the form of pie-charts in FIG. 6. The composition of the e-liquid was very close to the nominal e-liquid composition. The 55%-Kaolinite gel contains an increased proportion of glycerol. Because these samples required a longer heating time therefore also a longer pumping time, we suspect that the PG and nicotine components may be pulled through the collection pad along with some water content.

(41) Thermal Stability of Additives:

(42) Although the only volatile components of the formulated gels are the e-liquid components, compounds produced by thermal degradation of the gels could contribute volatile toxicants and undesirable flavor to the aerosol. Thermogravimetric analysis was performed on the gel additives to characterize the temperature at which they decomposed and give-off volatile components.

(43) Thermogravimetric analysis on the dry powder gel additives was performed using a Shimadzu TGA-50. Each sample weighed 15-20 mg and were heated in an open aluminum pan (VWR 12577-060). The additives were heated to 600° C. at a rate of 20° C./min in an air atmosphere at a flow rate of 100 mL/min. Combined thermogravimetric analysis and differential scanning calorimetry were performed of fully formulated gels using a TA Instruments Q600. The samples were placed in covered alumina pans and an identical covered alumina pan was used for the DSC reference. Simultaneous TGA and DSC data was collected analyzed by heating to 400° C. at 10° C./min with a gas flow rate of 100 mL/min air.

(44) Kaolinite did not show any signs of degradation in the relevant temperature range. Thermogravimetric analysis data for Kaolinite is shown in FIG. 7.

(45) Various modifications and variations of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in chemistry or related fields are intended to be within the scope of the following claims.