PLASTICISED SUPERPOROUS HYDROGEL

Abstract

The invention provides a process for preparing a plasticised superporous hydrogel material comprising subjecting initial hydrogel material to treatment with an acidic solution, an optional treatment with a monovalent metal salt solution, freeze drying and plasticisation. Optionally, the process of the invention produces moulded plasticised superporous hydrogel material bodies that have one or more through-holes formed therein. The plasticised superporous hydrogel material of the present invention may be formulated as a suitable oral dosage form for use an appetite suppressant and for use to deliver a pharmaceutical and/or nutraceutical into a human or animal body.

Claims

1. A process for preparing a plasticised superporous hydrogel comprising the steps: a) forming an initial hydrogel material in the absence of any blowing agent or other foaming means, wherein the initial hydrogel material comprises one or more selected from interpenetrating network structure, a semi-interpenetrating network structure and a simple cross-linked structure formed by providing a mixture comprising one or more hydrophilic polymers and/or copolymers and subjecting the mixture to polymerisation and/or cross-linking conditions; b) recovering the resulting initial hydrogel material formed in step a) and treating it with an acidic solution comprising one or more acids, and with a pH of ?3; c) treating the initial hydrogel material formed in step a), either concurrently with, or after, treatment step b), with a ?0M to ?0.5M solution comprising one or more monovalent metal salts; d) drying the resulting wet initial hydrogel material using freeze drying, to produce a dried superporous hydrogel material; e) treating the resulting dried superporous hydrogel material to plasticise its structure; and f) recovering the resulting plasticised superporous hydrogel material.

2. The process according to claim 1 wherein the resulting plasticised superporous hydrogel material is in the form of an individually separate samples comprising a body that has an internal structure comprising plasticised superporous hydrogel material and an outer surface, wherein each sample comprises one or more through-holes which form a passageway that extends within the internal structure of the body and between a first opening in a first portion of the outer surface of the hydrogel material body and a second opening in a second portion of the outer surface of the hydrogel material body.

3. The process according to claim 1, wherein individual samples of the initial hydrogel material are prepared by filling suitable moulds with a reaction mixture comprising one or more hydrophilic polymers and/or copolymers, prior to subjecting the mixture to polymerisation and/or cross-linking conditions, and demoulding the resulting individual samples of the initial hydrogel material.

4. The process according to claim 3, wherein the individual samples of the initial hydrogel material are cube-, cuboid-, ovoid-, pellet-, bead-, ball-, cylinder-, rod- or irregularly-shaped.

5. The process according to claim 1 wherein step e) includes subjecting the superporous hydrogel to >50% humidity conditions.

6. The process according to claim 1 wherein the one or more monovalent metal salts is a water-soluble alkali metal salt.

7. The process according to claim 1 wherein the one or more acids are selected from an inorganic acid and/or an organic acid.

8. The process according to claim 1 wherein the acidic solution comprises one or more selected from gastric fluid and simulated gastric fluid.

9. The process according to claim 1 further comprising the step of applying a compressive force to the resulting plasticised superporous hydrogel material to reduce the volume of at least some of the pores therein.

10. The process according to claim 1 comprising a further step of inserting the resulting plasticised superporous hydrogel material into a capsule dosage formulation shell to produce a capsule dosage formulation.

11. The process according to claim 10 wherein the resulting plasticised superporous hydrogel material is inserted into the capsule dosage formulation shell using one or more techniques to reduce the overall size of the resulting hydrogel body prior to insertion into the capsule dosage formulation shell, selected from: the exertion of pressure, folding, extrusion, and the application of bi- and/or tri-lateral compression.

12. The process according to claim 11 wherein the resulting plasticised superporous hydrogel material is extruded through a hollow tapered tube prior to insertion into the capsule dosage formulation shell.

13. The process according to claim 1 wherein the initial porous hydrogel material comprises one or more hydrophilic polymers derived at least in part from an acrylamide monomer or an acrylamide moiety-containing monomer.

14. A method of forming a formulation suitable for oral administration comprising including one or more plasticised superporous hydrogels prepared by the process of claim 1.

15. The method according to claim 14 further comprising including one or more pharmaceuticals and/or nutraceuticals.

16. An oral dosage formulation comprising one or more plasticised superporous hydrogels prepared by the process of claim 1 optionally together with one or more pharmaceuticals and/or nutraceuticals.

Description

DESCRIPTION OF THE DRAWINGS

[0063] The invention will now be described with reference to the representations in the following Figures, in which:

[0064] FIG. 1A: shows a cross-sectional view of a mould containing an initial hydrogel material prior to sealing;

[0065] FIG. 1B: shows the same cross-sectional view of the same mould depicted in FIG. 1A after sealing;

[0066] FIG. 2A: shows an end-on view looking at the circular end surface of a cylindrical sample of plasticised superporous hydrogel drilled with a through-hole along its central longitudinal axis, and the circular end surface of a cylindrical compression rod prior to it being used to compress the hydrogel sample;

[0067] FIG. 2B: shows a cylindrical compression rod being used to compress the cylindrical sample of plasticised superporous hydrogel depicted in FIG. 2A;

[0068] FIG. 2C: shows the cylindrical sample of plasticised superporous hydrogel depicted in FIG. 2B about to be folded in the direction of the arrows using the compression fold made in its surface by the cylindrical compression rod (removed);

[0069] FIG. 2D: shows the cylindrical sample of plasticised superporous hydrogel depicted in FIG. 2C after folding to reduce its diameter.

[0070] FIG. 3: shows a cross-sectional view of two folded cylindrical samples of plasticised superporous hydrogel inserted into a hollow tapered cylindrical mould and a push rod;

[0071] FIG. 4A: shows a cross-sectional view of a folded cylindrical sample of plasticised superporous hydrogel inserted into a hollow open-ended cylindrical mould with two push rod, one inserted in each of the two open ends of the mould;

[0072] FIG. 4B: shows a cross-sectional view of the folded cylindrical sample of plasticised superporous hydrogel inserted into a hollow open-ended cylindrical mould as shown in FIG. 4A, with the two push rods compressing the sample on opposing sides;

[0073] FIG. 4C: shows the sample of compressed folded plasticised superporous hydrogel shown in FIG. 4B following demoulding from the hollow open-ended cylindrical mould;

[0074] FIG. 5: shows a graph of the volume swelling ratio versus time, using either water or simulated gastric fluid as the swelling medium, for the compressed folded plasticised superporous materials produced according to the control Example 1 (#OG) and the present invention present invention in Example 2 (#NG);

[0075] FIG. 6: shows a graph of the swelling diameter profile against time, using either water or simulated gastric fluid as the swelling medium, for the compressed folded plasticised superporous materials produced according to the control Example 1 (#OG) and the present invention Examples 2 (#NG);

[0076] FIG. 7: shows a graph of true stress versus time, using either water or simulated gastric fluid as the swelling medium, for the compressed folded plasticised superporous material produced according to the control Example 1 (#OG);

[0077] FIG. 8: shows a graph of engineering stress versus time, using either water or simulated gastric fluid as the swelling medium, for the compressed folded plasticised superporous material produced according to the control Example 1 (#OG);

[0078] FIG. 9: shows a bar graph showing the 4-day strength in simulated gastric fluid of the compressed folded plasticised superporous material produced according to the present invention in Example 2 (#NG).

SPECIFIC EXAMPLES

[0079] The abbreviations used herein are defined as follows:

TABLE-US-00002 TABLE 2 Abbreviation Chemical AAm Acrylamide AL Alginic acid sodium salt APS Ammonium persulfate, BAC N,N bis(acryloyl)cystamine CaSO.sub.4 Calcium sulfate dihydrate Cellulose Cellulose DW Distilled water TEMED N,N,N,N-tetramethylethylenediamine SGF Simulated gastric fluid without pepsin (0.2%/wt sodium chloride and 0.7%/wt hydrochloric acid solution; pH = 1.2)

EXAMPLE 1: (CONTROL)

Example 1: (Control) The Preparation of Plasticised Superporous Hydrogel Material (PSH) with One or More Through-Holes Formed Therein to Assist in the Folding of the PSH to Reduce its Size and to Facilitate the Preparation of an Oral Dosage Formulation

Synthesis and Polymerization

[0080] 16.0 g (+/?0.1 g) of AAm and 99.0-132.0 mg (+/?1 mg) BAC were weighed and mixed with 90-200 ml of DW. Meanwhile, 20.0 g (+/?0.5 g) of AAm into a 6.0 g (+/?0.1 g) AL were weighed and mixed with 160-290 ml of DW. The above two solutions were mixed together with 433.0-751.0 mg (+/?1.0 mg) of APS, and the resulted solution was equally distributed into 8 smaller beakers (marked as Group A).

[0081] Into each of another 8 beakers (marked as Group B) was weighed 150.0 mg (+/?1.0 mg) of CaSO.sub.4 powder, 6.2 ml water and 47-82 ul TEMED.

[0082] The solution in one of the 8 beakers in Group A was poured into with the suspension in one of 8 beakers in Group B. The mixture (14) was then stirred for 10-50 seconds and poured into 4-8 moulds (10). Each mould consisted of a cylindrical polypropylene (PP) tube (12) with an internal diameter of 10-40 mm and top and bottom matching conical rubber stoppers (16, 18) with the same external diameter. The rubber stoppers (16, 18) in the tube mould (10) as shown in FIGS. 1A and 1B.

[0083] Similar operations were repeated for all 8 sets of solutions in Groups A & B, and all the samples in the PP moulds (10) were left in an incubator (preheated to 60? C.) for 1 hour. The moulds (10) were then transferred into a humid chamber to cure for another 24-72 hours at room temperature for the completion of polymerization. The resulting gelled materials (initial hydrogel materials) were labelled as the as-prepared gels (APGs).

Freezing & Freeze-Drying

[0084] The APG gels in their respective mould (both ends of which were sealed with rubber stoppers), were left in a ?20? C. freezer for 8-24 hours and then transferred into the freeze-dryer to remove the water from the frozen gels over a period of 48 to 72 hours. This produced freeze-dried superporous porous hydrogel (a freeze-dried SPH).

Formation of Through-Holes

[0085] One or more through-holes or channels of diameter 4 to 10 mm were drilled along the longitudinal axis of each cylindrical sample of freeze-dried SPH to form a drilled freeze-dried SPH. The swarf was blown off, for example using a fan.

Plasticisation

[0086] A lidded container half filled with water and including a sample holder which could float on the water in the container were left in the incubator of 60? C. for 24 hours. A sample of drilled freeze-dried SPH was then put in the sample holder and left inside the container for 30 to 60 min until it became malleable.

Compression

[0087] The malleable (plasticised) drilled freeze-dried SPH (20, 26)) was carefully removed from the container and compressed along the hole (22, 25)) from the lateral side of the sample with a rod (24), folded along the compressed line (28) to form a folded plasticised drilled freeze-dried SPH (30) as shown in FIG. 2D, and then either squeezed through an open-ended tapered tube to reduce its size to that of an oral dosage capsule, as sown in FIG. 3, or squeezed into a cylindrical tube and compressed with push rods (38a and 38b), each having a concave end (40a, 40b) and each inserted into opposing open ends of the cylindrical tube (36), as shown in FIGS. 4A and 4B, or directly moulded in a capsule mould.

Example 2: The Preparation of a Superporous Hydrogel Material Using the Process of the Present Invention Using an Acidic Solution to Treat the Precursor Initial Hydrogel Material and Forming One or More Through-Holes in the Body of the Sample when at the Superporous Hydrogel (SH) Stage to Further Assist Processing the PSH Material into a Lozenge-Shaped Shaped Body

[0088] The synthesis and polymerisation step used in Example 2 to form the initial hydrogel material, was exactly the same as used in Example 1.

Treatment with an Acidic Solution

[0089] The rubber stoppers (16, 18) were removed from the mould (10) shown in FIG. 1B, and DW was used to wet the interface between the APGs and the PP tubes (12) so that the APGs could slide out from the tubes for the next washing process.

[0090] The APGs were submerged in SGF (at a pH of around 1.3) for 7-14 days with a daily routine of flushing the samples and containers with DW as well as refreshing of the SGF. The volume of the SGF used to soak the samples was 15?50 ml per gel.

Freezing & Freeze-Drying

[0091] The expanded and acidic solution washed samples were drained from the SGF, and each hydrogel was directly put into a PP cylindrical tube mould which has a similar diameter to that of a swollen gel. The swollen gel inside the mould was then put into a ?20? C. freezer for 8-24 hours and then transferred into the freeze-dryer to produce a freeze-dried superporous hydrogel (freeze-dried SPH).

Formation of Through-Holes

[0092] One or more through-holes or channels of diameter 4 to 10 mm were drilled along the longitudinal axis of each cylindrical sample of freeze-dried SPH to form a drilled freeze-dried SPH. The swarf was blown off, for example using a fan.

Plasticisation

[0093] A lidded container half-filled with water and including a sample holder which could float on the water in the container were left in the incubator of 60? C. for 24 hours to ensure a uniform temperature. The freeze-dried SPH with a hole was then put in the sample holder and left inside the container for 5 to 20 min until it became malleable.

Compression

[0094] The malleable (plasticised) freeze-dried SPH sample was carefully removed from the container and as shown in FIGS. 2A and 2B compressed along the hole (22) from the lateral side of the sample (20) with a rod (24) and folded along the compressed line as shown in FIGS. 2C and 2D and the resulting folded sample (30) of plasticised freeze dried super porous hydrogel was squeezed, as shown in FIG. 4A, into a cylindrical tube (36) with an I.D of 9?10 mm. Two studs (38a and 38b) (O.D 9?10 mm) with a specially made dome concave on one end (40a and 40b) were put on either side of the sample (30) in the tube (36) and were pushed towards the centre to form the round ended hydrogel capsule (42) which was then removed from the tube as free capsule (lozenge-shaped body) (44) as shown in FIG. 4C.

Results

[0095] The degree of swelling can be measured in several different ways, for example: [0096] 1) by recording the change in size by placing the samples before and after swelling on a calibrated grid (1 cm squares). [0097] 2) using a displacement method in which the initial volume of a dry gel is first measured using an ethanol displacement method. The gel is put in a measuring cylinder filled with pure ethanol and is pushed down by a thin needle to just submerge the ethanol. The displacement of the liquid level is calculated and taken as the initial volume of the dry gel. When the amount of displaced ethanol is measured, the gel is removed from the ethanol, dried (for example using a clean tissue) and left in the fume hood for 1 hour to evaporate the remaining ethanol before the gel sample is put in a swelling media (e.g. water or SGF). Upon completion of swelling, the swollen gel volume is determined using the same liquid-displacement method as immediately mentioned above but using the swelling medium as the liquid in place of the ethanol. The difference between the volume of displaced ethanol and the volume of displaced swelling liquid is used to determine the swelling volume ratio for the gel. [0098] 3) measuring the length and diameter of hydrogel samples before, and after swelling using callipers.

[0099] Examples 1 and 2 both produced compressed plasticised superporous hydrogel materials, however the material produced in Example 2 (#NG) achieved faster-swelling results with the maximum swelling size being achieved in around 20 min (in SGF and water), as compared against the hydrogel made using Example 1 (#OG) which needed more than 60 minutes to achieve the same degree of swelling.

Summary of the Results

[0100]

TABLE-US-00003 TABLE 3 SUPERPOROUS SUPERPOROUS HYDROGEL MADE HYDROGEL MADE USING CONTROL USING EXAMPLE EXAMPLE 1 (#OG) 2 (#NG) Swelling Fast-swelling: can swell Superfast-swelling: Swelled rate to the critical size to 8-10X in 10 min; can (>20 mm in diameter) swell to >25 mm in 20 min within 60 min in water in both water and SGF Volume Volume swelling ratio of Volume swelling ratio of Swelling 18-20X in water (14 days) 10-12X in both water and ratio 8-12X in SGF (14 days) SGF (1 day) (See FIG. 5) (See FIG. 5) pH The swelling ratio pH has no effect on either sensitivity is1.5-2.5X larger in the swelling rate or the (The effect water (pH 7) than SGF swelling ratio of pH on (pH 1.2) swelling The time taken to get to ratio) 15% volume increase is faster in water when compared to the time for SGF solution) Mechanical Elastic; less flexible; water Spongy; more flexible property cannot be squeezed out. compared with the material of Engineering stress at the Example 1; lower elastic point of breaking (measured modulus (as determined by using a force meter the observed ease of calibrated in pressure units) compression as measured by 60N (168 kPa) ?> a force meter) (deform more 27N(94 kPa) from day 1 ?> upon compression); water can day 14 in water be squeezed out 82N(229 kPa) ?> Engineering stress at the 45N(154 kPa) from day 1 ?> point of breaking (measured day 14 in SGF; using a force meter calibrated 73N (180 kPa) @ Day 3 in in pressure units) SGF (See FIG. 8) 81N (182 kPa) @Day 4 in SGF Max True stress at breaking Similar results are observed in point (measured using a water force meter) Max True stress at breaking 7.7N(58 kPa) ?> 1.4N(10 kPa) point (measured using a force from day 1 to day 14 in water; meter) 9.6N(72 kPa) ?> 3.3N(25 kPa) 46N (349 kPa) @Day 4 in SGF in SGF (see FIG. 9) 7.7N (58 kPa) @ Day 3 in SGF (see FIG. 7) Processing Steaming time: 30 min Steaming time: 5-15 min Lead time: 27-30 days Lead time: 15 days Potentials Can be made less spongy by using less water initially without compromising the fast- swelling ability; Can change the freezing method (sealing) to change the crystal structure and pore size to slow down the initial swelling rate.

Example 3: Experiment to Investigate the Effect of pH on the Appearance and Swelling Performance of Plasticised Superporous Hydrogel Material Made by the Process of the Present Invention

[0101] The synthesis and polymerisation step used in control Example 1 was used to prepare thirteen (13) separate samples of initial hydrogel material, each individually cast in a mould (10). Each moulded sample was then treated in accordance with the present invention, as follows.

Treatment with an Acidic Solution

[0102] The rubber stoppers (16, 18) were removed from each mould (10) shown in FIG. 1B, and DW was used to wet the interface between the APGs and the PP tubes (12) so that the APGs could slide out from the tubes for the next washing process.

[0103] Each of the APG samples was submerged in its own acidic solution, with a different pH for each and being between pH 1 and 12, and the thirteen APG sample being submerged in SGF (at a pH of around 1.3), for 7days. The volume of the acidic solution used to soak the samples was 15?50 ml per gel.

Freezing & Freeze-Drying

[0104] The expanded and acidic solution washed samples were drained from the final acidic solution, and each acid treated hydrogel sample was directly put into a 30 mm diameter cylindrical tube mould that should be longer than the length of gel and have only one end open. The swollen gel inside the mould was then put into a ?20? C. freezer for 8-24 hours and then transferred into the freeze-dryer to produce a freeze-dried superporous hydrogel (freeze-dried SPH).

Plasticisation

[0105] Each sample of freeze dried superporous hydrogel was plasticised using the following method. A 0.4 L lidded container with an inner surface that includes a moisture wicking material (for example, strips of moisture absorbent paper, moistened with 1 ml of water each). The container is heated to 60? C. for 5 minutes. A freeze-dried SPH sample was then put in the container (well away from the moisture wicking material) and the container replaced in the oven at 60? C. for 1 to 5 minutes (ideally 3 minutes) until the sample became malleable.

Compression

[0106] Each malleable (plasticised) freeze-dried SPH sample was carefully removed from the container and as shown in FIGS. 2A and 2B compressed along the hole (22) from the lateral side of the sample (20) with a rod (24) and folded along the compressed line as shown in FIGS. 2C and 2D and the resulting folded sample (30) of plasticised freeze dried super porous hydrogel was squeezed, as shown in FIG. 4A, into a cylindrical tube (36) with an I.D of 9?10 mm. This was achieved using a crimping machine that applies even radial compression along the long axis of the sample. The degree of swelling was measured by recording the weight of each sample of SPH material prior to swelling in distilled water at 37 C and recording the length and diameter of each swollen sample and noting the expansion % volume over time.

[0107] RESULTS As shown in Table 4 below, the SPH samples show an increase in % expansion as the pH of the acidic treatment solution increases from 1 to 12, with the greatest increase being recorded for the initial hydrogel samples treated with an acidic solution of from pH 1 to 3. Initial hydrogel samples treated with acidic solutions with a pH of 4 to 11 produce SPH samples which continue to increase in % expansion but the rate of this increase plateaus, and when a treatment solution of pH12 is used, the respective SPH sample disintegrates.

TABLE-US-00004 TABLE 4 Expansion pH Appearance Shape % wt 1 translucent Defined cylinder 16.8 SGF (pH 1.3) translucent Defined cylinder 17.0 2 hazy Defined cylinder 22.6 3 Slightly hazy Slightly distorted cylinder 30.2 4 transparent Distorted cylinder 32.5 5 transparent Distorted cylinder 33.9 6 transparent Distorted cylinder 35.4 7 transparent Distorted cylinder 28.7 8 transparent Distorted cylinder 31.7 9 transparent Distorted cylinder 32.8 10 transparent Very Distorted cylinder 35.6 11 transparent Very Distorted cylinder 42.5 12 transparent Amorphous 90.1

[0108] Other key observations made during this experiment include: i) as the pH of the acidic solution used to treat the initial hydrogel is increased, the target SPH become less mechanically stable. This is observed by the loss of structural integrity in the SPH sample; the SPH sample has defined cylinder shape when an acidic treatment solution on pH 1 to 3 is used, but this shape becomes progressively more distorted as the pH increases to pH 11, and finally becomes amorphous when the treatment solution is at pH 12. ii) Although expansion increases as the pH of the acidic solution used as the soaking liquid increases, the target SPH material becomes progressively more unusable. iii) A desirable hazy/translucent appearance in the SPH is only observed when the initial hydrogel from which the respective SPH sample is formed is treated with an acidic solution with a pH of 1 to 3. It is understood that this haziness/translucence is caused by the porosity in the hydrogel.

[0109] The time needed to treat each sample with high humidity conditions was found to vary significantly, depending on the pH of the acidic solution.

[0110] CONCLUSION: The pH of the acidic solution used to treat the initial hydrogel material is particularly important for to ensure good processability and must be less than or equal to pH 3 to provide optimum conditions for the desired pore size and desired rate of expansion, whilst maintaining structural integrity.

Example 4: Experiment to Determine the Effect of pH and Treatment with Potassium Chloride on Swelling Behaviour

[0111] The synthesis and polymerisation step used in Example 1 was used to prepare twenty (20) separate samples of initial hydrogel material, each individually cast in a mould (10). The samples of initial hydrogel material were then split into four (4) batches; one batch was treated with an acidic solution at pH 1, another treated with a solution at pH 1.3, another with a solution at pH 2 and the remaining treated with a solution at pH 7. The five samples in each batch were then treated with an aqueous solution containing from 0M to 1M of potassium chloride salt. Following this, each of the samples were freeze dried, plasticised and compressed, as described above in Example 3, and the resulting shaped SPH samples were immersed in distilled water at 37 C and recording the length mm and diameter mm of each swollen sample and noting the expansion % volume over time.

[0112] The complete experiment was repeated 4 times and each % volume increase value presented in Table 5 below, is an average of the four results obtained for the corresponding samples from each repeat of the experiment. The results show that the concentration of potassium chloride has very little effect on the final swelling weight on soaking, in the case of samples produced from initial hydrogel samples that are treated with an acidic solution with a pH of 1 to 2, although as expected from Experiment 3 above, a much larger % weight increase is observed when the treatment solution is at pH 7. However, very surprisingly, it is found that the % volume change after 60 minutes is effected by the concentration of potassium chloride; specifically, the % volume expansion increases as the concentration of potassium chloride increases from 0M to around 0.134M (10 g), and then the expansion decreases when the concentration reaches around 0.5M.

[0113] CONCLUSION: >0 to 0.134M addition of KCl is a particularly useful range.

TABLE-US-00005 TABLE 5 % volume % volume Amount of increase after increase after pH of KCl in 10 mins 60 mins Acidic the salt (Results are (Results are treatment treatment an average of an average of solution solution 4 repeats) 4 repeats) Wt % pH1 0 200 265 23.4 0.067M 188 318 22.9 0.134M 233 361 24.7 0.5M 132 285 26.1 1M 231 323 27.9 pH 1.3 0 216 337 23.8 0.067M 162 352 24.0 0.134M 92 318 23.6 0.5M 78 368 25.2 1M 65 156 24.5 pH2 0 74 173 28.2 0.067M 64 227 26.1 0.134M 56 164 24.7 0.5M 47 111 23.5 1M 41.4 pH7 0 269 126 40.4 0.067Mg 110 379 41.1 0.134M 119 338 44.8 0.5M 100 180 40.2 1M 106 198 44.3 sgf 105 214 24.1

Example 5: Experiment to Determine the Effect of Monovalent Metal Salt Concentration on the Processability of the Target SPH Material

[0114] An important property of the required plasticised superporous hydrogel material is the ease with which it undergoes shaping, for example by folding/rolling/compressing, to enable it to be inserted it into a dosage capsule shell within a reasonable time frame, (desirably more than 1 minute but less than 60 minutes) and there is a fine balance between an SPH material that has excellent workability characteristics, and one which has become too soft. The present work has surprisingly established that for a given degree of water vapour treatment (exposure to moisture: % humidity and duration) used to plasticise an SPH sample, the workability (ease of folding/rolling/compressing) of the SPH sample increases as the KCl concentration increases, the SPH material become more workable. However, too much KCl, typically when the metal salt concentration is above 0.15M, the target SPH becomes too soft to be worked easily.

[0115] A useful outcome of this observation is that the addition of KCl assists to control and optimise the amount of moisture exposure (duration and/or % humidity) a sample of dried SPH material needs to soften it, with concentrations of KCl salt >0M up to 0.15 M enabling a reduction in humidity/shortening the time of moisture exposure, compared with the case when no KCl salt is used.

[0116] CONCLUSION: Optimal moisture exposure is obtained when a >0M to 0.15M monovalent salt solution is used.