1.1 Introduction

In recent decades the general rate of population all over the world start aging. Ageing results from development of medical care and the ability to prevent fatal disease by imposing vaccination and evolve of medications which have capabilities to eliminate many types of illness and also enhance the quality of life. These factors lead to decreasing mortality particularly in developed countries, declining fertility rate may also play an important role in ageing propagation through communities which leads to reduction in proportion of children and increase older persons in population (Grant, et al, 2004). The World Population Aging Report (United Nations, 2013) observes that the global rate of older people between 60 years of age or over increased from 9.2% in 1990 to 11.7% in 2013 and will continue to rise and could be reaching 21.1% by 2050. In this context, chronic and complicated diseases predominantly associated with advancing age, a considerable proportion of elderly people principally over sixty years old suffering from disability, mental disorders such as Alzheimer or psychotic disease, forgetfulness,  the problem is compounded especially if they are on multiple types of medications, risks such as repeating, missing, and incompliant of medications dose might affect their life quality and health which subsequently  lead to depression  and even death (Suh, et al, 2009),  a sustain release drugs could  be useful solution for those type of patient, Sustain release drug delivery system can be identified as a regulation of drug delivery that assist  slower or steadier releasing of a single dose over a period of time which prolong the therapeutic effect, decrease dose frequency and detraction of peak fluctuation for blood concentration  which reduce possible side effects enhance drug bioavailability and could also improves drug distribution (figure 1), the advantages of this technique for elderly patients is significant relating to decrease the number of doses, avoid night doses which improve patient compliance and provide a better control of the disease status, additionally it might increase safety by reduce fast absorption of high potency drugs in the plasma level therefore maximise utilization of the single dose, reduce health costs , and supply better control of drug absorption rather than the conventional immediate release tablet (Dixit, et al, 2013)

In contrast, Pradesh, District (2013) point out that if there is a toxic substance within sustain release formulations it will stay in the body after administration for a long period of time, and then the body will take a long time to completely eliminate the toxic material and that’s lead to difficulty in titrating patients and inflexible dose scheduling.

 

 

Figure 1: Drug release from sustained release delivery system. Here drug substance is coated by a release control polymer (either a natural resin or a synthetic polymer).

 

 

 

In addition, recent surveys have shown that many elderly patients are suffering from dysphagia or difficulty of swallowing, in principle, the oral route is the favourable way for drug administration, hence swallowing difficulties is considered as substantial obstacle and a major challenge for safety and efficacy of medicine especially when elderly patients intend to administer their medications by oral route.

Kelly et al. (2009) indicated that 35-68% of older people had difficulty of swallowing, and it is not solely complicate digesting of food process and drinks fluid but it also includes swallowing of oral medications. A survey of 477 patients in England who had dysphagia reveals that 68% (n= 324) were trying to open capsules, crush the tablets, or even mix the powder with drinks or food for being easier to swallow, problems like carcinogenesis it seems to be occurred when patients did that with anticancer drugs, in addition such process would delay or accelerate the absorption rate of drugs which could lead to severe side effects due to drug overdose and toxicity or delay the appropriate absorbing rate of that’s type of dosage form then prolonged the illness symptoms, moreover degradation of the active ingredients of enteric coating tablets like omeprazole in a stomach its result from destroying the protective layer of tablet and many kinds of antibiotic, and then being inactive after exposing to the stomach acids, therefore this method  prevent those tablets from exert their actions after they will absorbed from intestine (Mitchell J, 2008), were 64% (n=305) of them refused taking their oral drugs when prescribed due to they had dysphagia.

A significant harm particularly occurred with modified release formulations due to they usually contain larger dose than the conventional release tablets. Crushing tablets or opening capsules is prohibited with modified release formulations because such process can disrupt the releasing profile of the drug and produce drug overdose which lead to toxicity. The problem can be primarily solved by the physicians or the pharmacist by omitting any unnecessary medication or prescribing a combinational drug which has more than one active ingredient in one drug dose, and finding an alternative pharmaceutical dosage form such as, sublingual, Buccal tablets, suppositories, inhalations, transdermal, or another medicine with comparable pharmacological effect would be prescribed, for instance, transdermal glyceryl trinitrate patches instead of modified-release isosorbide trinitrate, however the problem might manifest  if there is no pharmaceutical dosage form replacement then the patient will find himself compelled to accept oral medication (Kelly et al. 2009)

In this perspective, a convenient sustain release drugs for dysphagic patients getting a profound importance in last years, many pharmaceutical industries were trying to overcome these hassles.

 

-Approaches to ease drug administration of sustain release formulations for patients with dysphagia:

Ionic exchange resin:

Hirsh et al. (2004) pointed out that a progression has been made for sustain release drug formulation in context of facilitate swallowing. The drug composition can be complex with ion exchange resin to form a tiny multi particulate less than 150 microns, the drug-resin complex resulted from binding with the salt form of the drug, at that point the resin can coat the active ingredient of the drug to prompt modified release property. The coating materials comprise of an aqueous dispersion of a synthetic polymer for example: poly (ethylacrylate  methylmethacrylate-triethylammonioethylmethacrylate Chloride).  At that juncture these can be ultimately formulated into the ending dosage form like: gel, soft gelatine capsule, suspension, rapidly dissolving tablet chewable tablet, and sachet for reconstitution to create easier swallowing dosage form. Similarly, Ichikawa, et al. (2001) emphasize that using of drug ion exchange resin complex as a core particle has the ability to form 100 μm- microcapsules sized and it can produce sustain release property, the drug can be loaded in anionic exchange resin then fractionated into 200–400 mesh and then microencapsulated with Eudragit® RS30D, in other embodiment, Cherukuri (2012) explains that rapid disintegrated controlled release tablet which is dissolve quickly in the mouth can be a substitute choice for paediatric or geriatric patients who have difficulty in swallowing and its effectiveness is similar to conventional capsules or tablets (Figure 2)

Figure 2. In vitro-drug release (cumulative percent drug release) of the Dextromethorphan HBr from the rapid melt controlled release tablets in1.2 pH followed by 6.8 pH phosphate buffer. (Cherukuri 2012)

 

Complexing of the drug active ingredient Dextromethorphan with resin can cover unpleasant flavour by adsorbing into ion exchange resin.  Strong acid cation resins (sulfonated styrene-divinyl benzene copolymer products) can mask basic drug’s unpleasant flavour while strong basic cation resin has the ability to cover acidic drug unpleasant flavour.

However, there is concerned with this technique such as poor compressibility due to the existence of resin. The coated particles of drug-resin composite agglomerate during compression which can be resolved by applying the lowest compression force, which also leads to an extended control release of the medication.

In situ gelling sustained release:

In situ gelling formulation intended for sustain release drug delivery is consider as a useful style for dysphagic patients. Itoh et al. (2011) clarify that gels formed by addition of pectin (0.5–2.0%) and methylcellulose (1.0–2.0%) with 20% d-sorbitol and calcium ions in compound improve the gel strength formulation and viscosity can stimulate comfort administration for dysphagic patients, then after administration the gel will formed in situ reserved their integrity in stomach for appropriate time for sustained release to be attained, Methylcellulose is a water soluble polysaccharide that can form a thermoreversible hydrogel in water by being heated at 55C˚above and by adding sorbitol the temperature can be reduced to be more convenient to body temperature. Whereas pectin is anionic polysaccharide which could form hard gel when compounding it with calcium through ion responsive gelation. The combination can form thermo-ion responsive vehicle oral sustained drug delivery which is achieved in situ gelation and is more complimentary for dysphagia patients.

Likewise, Miyazaki et al. (2009) highlight that gel formulation encompasses of gelatin, agar, gallan, pectin, and xyloglucan and can produce oral sustained drug delivery system to dysphagic patients,

where Gellan (1.5% w/v) and xyloglucan gels (1.5% w/w) deliver ease of oral administration mostly as a liquid and then can be transformed to the gel in the acidic media as stomach to attain sustain release property. In situ gelation of gallen and pectin solution is prepared by complex nonionise calcium++ to release free Ca + ions when reached to acidic media in stomach and prompt immediate gelation which act as a vehicle for oral sustained drug delivery. Shimoyama et al. (2012) observe that patients with dysphagia capitalize from liquid dosage form using in situ gelling characteristics. A mixture of solution containing methylcellulose (2.0%) and sodium alginate (0.25–1.0%) with 20% d-sorbitol was accomplished comfort of administration as a liquid and it transformed to gel in the stomach to implement sustained release.

Microparticulate sustain release:

Yamada et al (2001) indicate that a microparticulate of ketoprofen (420–600 μm) can be settled as sustained release. An increment of patient compliance is attained by decreasing dose frequency principally for those patients who are distressed from chronic diseases like rheumatoid arthritis or pain. The core of the micropariculate has ketoprofen as an active ingredient, Eudragit L100, and calcium salt to increase drug solubility.

While the covering material contains carboxymethylethylcellulose, and ethyl cellulose, which provides ketoprofen control release.

After primary prompt release, the microparticles deliver a constant plasma level, and can be existing as sustained release.

Xiao et al. (2015) reveals that curcumin anti-inflammatory drug loaded microparticles can perform as sustain release drugs for ulcerative colitis where the manufacture of microparticles has been prepared by the emulsion solvent evaporating method with modified pH sensitive Eudragit (S100), poly lactide-co-glycolic acid (PLGA) and microparticles were loaded with curcumin to yield 1.52 to 1.91 μm particle size. The existence of (PLGA) can reduce curcumin release from microparticles to show sustain release orally administrated which is reflect valuable ulcerative colitis cure.

Correspondingly, Mittal et al. (2007) indicate that estradiol can be loaded in poly lactide-co-glycolic acid (PLGA) microparticle by the emulsion evaporation technique which can stimulate sustained release of the oral dosage form and improve bioavailability, whereas the release duration depend on particle size and molecular weight that increases when compact in size. Zhang et al. (2013) observe that diatoms which have porous silica based materials micropartilcles might load prednisone by the immersion process may supply sustained release formulation as well as offer safety of administration which is optimize patient compliance, and develops permeability.

Jelly and gel formulations:

Miyazaki, et al. (2009) state that gel formulations for oral administration is getting preference for dysphagic patients, Paracetamol can be loaded within these formulation with a proper rheological characteristics to achieve ease of swallowing, whereas the ability of gel to maintain their integrity in the acidic environment such in stomach enabling sustain release feature. The gel contain gelatine, gellen gum, pectin, agar, xyloglucan can provide a sufficient gel strength to exert prospective sustain release property. Similarly, Miyazaki, (2011) entailed that using of i –carrageenan for gel formulation provide better gel strength than agar gel, thus i –carrageenan has superior sustain release feature, and their viscosity is convenient to use as vehicles for oral delivery of medications to patients suffering from difficulty of swallowing. Moreover Prakash, et al. (2014) agree that medicated jelly formulations are useful and convenient for patients suffering from difficulty of swallowing, although with presence of various dosage form such as: suspension, chewable tablet, solution, powder for reconstitution, many disadvantages occurred with them like: improper measurement, stability, dose waste, ease of administration especially if those patients administered syrup or suspension which may chocked them, this problem can be solved by using a thickening material to increase solution viscosity or using jelly formulation, jelly prepared from gellan gum, pectin, pectin-guar gum can be act as a drug vehicle for carbamazepine and could enhance their solubility, in addition to enhance dysphagic patients acceptability,

Satyanarayana, and Keshavarao. (2014) reveal that gels prepared by natural polymer like silk fibroin with a proper rheological properties can act as a salbutamol sulphate vehicle and it offer ease of administration for dysphagic patients, using of Fourier transform infrared spectroscopy and Differential scanning calorimeter (DSC) detect that the drug is biocompatible with their gel vehicle, while in vitro release show that the formulation are able to sustain drug their release up to 90 minutes.

1.3 Aim and objective

the aim of this project is to perform an ideal jelly, investigate the property of each contributed material used in formulation and realize the correlation and interaction between them, in addition to the impact of those factors into the final formulation, in this context, former characterization assessment would be done by observe the visual appearance of those preparation for instance: assess visually if thickened fluid flow when invert their container, in contrast gel has to be not flowing when container is inverted, and whether if jelly formed a standing gel and if its hold their shape when cut by spatula and whether it quivers or wobbles in order to be easy for swallowing, and consider their colour and homogeneity, thereafter, evaluating if the vehicles are heterogeneous by present of swollen granules by using light microscopy, and ultimately testing the texture and rheology of the formulation by using texture analyser and rheometer instrument.

In essence such formulations can act as a drug vehicle where the active ingredient of the drug can be loaded into them with the ability to control drug release, in order to facilitate their administration by oral route principally for those patients suffering from dysphagia, further testing would be prepared to ascertained that these formulation attain their purpose, in vitro experiment by using an artificial throat can be testify whether that’s formulation passing smoothly through the throat or not (Weel, et al. 2004), The influence of the mixture on the drug properties such as drug content, and drug release, plasma concentration, and correlation between in vitro and in vivo release have to be examined (Yamada et al, 2001).

2. Materials and methods:

2.1 Materials: Different types of sodium alginate: (1740, 5450, 8223), Pectin, iota carrageenan, lamda carrageenan, Kappa carrageenan, Xanthan gum, Low acyl gellan gum, High acyl gellan gum, Gum Arabic, Gum Karaya, Gum tracaganth, Guar gum, Locust bean gum, Pregelatinised corn starch, Precooked acetylated di-starch phosphate (from potato), Precooked acetylated di-starch adipate (Waxy maize), Polyethylene oxide, Carbopol, HPMC s, Egg protein, Cekol 2000, Hartley’s readymade jelly, Hartley’s jelly powder.

Additional material needed for the test such as: Calcium chloride, calcium sulphate, calcium carbonate, Sucrose, Citric acid, Disodium hydrogen phosphate, Potassium dihydrogen phosphate, Tween 80, Potassium chloride, Sodium chloride, Maltodextrin, Glycerine, acetone, oasis summer fruit drink, Deionised water was used for all the experiments.

2.2 Methods:

Commercial brand jelly:

A commercial brand ready-made jelly prepared by heating process called Hartley’s contained: water, sugar, fructose syrup, gelling agents such as: locust bean gum, Xanthan gum, gellan gum, citric acid, has been brought to the lab to assess their characterization by using of different criteria such as: rheometer, and texture analyser, afterward consider the former jelly characterization as an ideal jelly to compare their properties to another jelly formulations prepared in the lab in order to enhance their properties.

Furthermore, another commercial brand jelly powder belong to the same company (Hartley’s) was obtained to prepare in the lab, the sachet content was poured into 500 mL beaker, while 300 mL of deionised water was heating in another beaker on hot plate to 100 C˚, after that the boiling water has been added to the beaker which contained that powder and magnetic stirrer, the beaker placed on stirring machine with 180 rpm speed to let the powder dissolve, then 200 mL of oasis summer fruit drink was added to the beaker for stirring until it thoroughly mixed through the solution, the solution was placed in fridge to form jelly.

Similarly, the previous jelly formulation undergone to the same characterization assessment criteria to identify their properties.

Lab prepared Jelly:

Posteriorly, different jelly preparation was performed in the lab by using two techniques, the first approach follow the traditional way of making jelly through applying heat during mixing gelling materials, 0.5% of Kappa carrageenan (100 mg) and 0.33% of locust bean gum (66 mg) were weighed by using weighing machine EP213, then poured to 100 mL beaker containing 20 mL of deionised water and magnetic stirrer placed on hot plate with 100 C⁰, the stirring with heating process operating till powder dissolved, after that the beaker transferred to the fridge to form jelly.

while the second technique used sodium alginate and calcium chloride, the privilege of this technique over the preceding one it’s the ability to form jelly in a short period of time, the jelly formed by dispersing sodium alginate (200 mg) in 10 mL of deionised water by using 100 mL beaker containing magnetic stirrer, and disperse calcium chloride in another 100 mL beaker containing 10 mL of deionised water and magnetic stirrer placed on multi-channel stirrer MS-52M with 180 rpm speed, once powder hydration occurred, calcium chloride solution was added into sodium alginate solution to form jelly.

Measuring sodium alginate hydration time by using stop watch is important to decide which sodium alginate type is dissolve faster in water.

Gelling material hydration time test:

1% (200 gm) of gelling material include: HM Pectin, LM pectin, iota carrageenan, lamda carrageenan, Kappa carrageenan, Xanthan gum, Low acyl gellan gum, High acyl gellan gum, Gum Arabic, Gum Karaya, Gum tracaganth, Guar gum, Locust bean gum, Pregelatinised corn starch, Precooked acetylated di-starch phosphate (from potato), Precooked acetylated di-starch adipate (Waxy maize), Polyethylene oxide, Carbopol, HPMC s, Egg protein, Cekol 2000, were dispersed individually in 100 mL beaker containing 20 mL of deionised water and magnetic stirrer, the hydration time of each material was recorded by using stop watch, other characteristic such as: formed material, visual appearance was observed, thereafter, the process was repeated by adding (1% of sucrose, 2% of sucrose, calcium sulphate, calcium chloride, calcium carbonate,  maltodextrin, tween 80, glycerol) to each material, the hydration time after the additive factor was recorded to find out whether the hydration time improved or retard, essentially this experiment can identify the formed material of each substance in water, and determine their hydration time in order to perform an instant jelly.

Jelly Development experiment:

This experiment intend to develop an instant jelly formulation characteristics  by testing different methods, then figure out which jelly characteristic is much appropriate:

1. as a first method the ratio between sodium alginate and calcium chloride remain constant (1:1%) for addition of 1% of other gelling material, the additional gelling material was added first to the beaker containing 1% of sodium alginate and 10 mL of deionised water, while the opposite beaker contained 1% of calcium chloride dispersed in 10 mL of deionised water, after powder hydration occurred, calcium chloride solution was added to the former beaker to form jelly.
2. Then as a second method 1% of the additional gelling material was added to 100 mL beaker contained 1% of calcium chloride and 10 mL of deionised water, while the opposite beaker contained 1% of Na alginate and 10 mL of deionised water, thereafter similarly, calcium chloride and new material solution was added to Na alginate beaker to form jelly, the difference such hydration time and visual appearance of each formulation was observed.
3. After that, another technique was processed in the lab to entail jelly development exploration procedure, a 75% = (1.5%) of sodium alginate verses 25% = (0.5%) of additional gelling material powder were mixed together then dispersed in 10 mL of deionised water, while the opposite beaker contained 1% of calcium chloride dispersed in 10 mL of deionised water, once the powder dissolved calcium chloride solution was added to the opposite beaker to form jelly.
4. Thereafter, as a fourth method 25% = (0.5%) of sodium alginate verses 75% = (1.5%) of additional gelling material powder were mixed together then dispersed in 10 mL of deionised water, while the opposite beaker contained 1% of calcium chloride dispersed in 10 mL of deionised water, once the powder dissolved calcium chloride solution was added to the opposite beaker, the hydration rate and the visual appearance for each mixture was observed for selection of the best jelly features.

After that the best jelly features figured out, the formulation process repeated again to assess their characterisation by using different criteria such as: the hydration time, weigh of formed jelly, water remained, visual appearance, the best two characteristics of them were obtained to determine their properties by using rheometer and texture analyser instrument, then compare their result with the commercial jelly result.

Rheometer test:

Steel plate (40 mm) was used for TA instruments AR1500ex Rheometer + Julabo AWC100 cooling system, nitrogen gas pressure gauge was turn into 20 Bar, Rheometer, Julabo, and computer was turn on, then rheology advantage application was used to measure the rheology of the samples, calibration was done to the intending force applying to the sample through option- instrument- calibration- calibrate inertia, then rotational mapping was prepared by press on the left, 5mm gap was selected from left zero gap icon, while 650 mm gap to calibrate the back-up, the stress step test was used firstly with 25 C˚ temperature, from oscillation process 0.1- 1000 torque and frequency 1 were chosen, direct your result to your file from choosing result destination in order to save it, thereafter suitable sample portion was transferred underneath the spindle force, then the spindle was moved down to the adjusted gap by pressing on left icon, after that bearing lock button was pressed to remove the sample waste from the edge of the plate, after that the test was run by pressing on the green upper left button, the response of the sample was recorded by the rheometer by applying various force, once the test finished, the remaining sample was removed and the spindle was cleaned for doing frequency sweep test, to prevent destroying the next sample the strain % was adjusted to 0.0300 from ƴ left icon, frequency sweep test was chosen from oscillation procedure and the same procedures were done to figure out the test result, after that steady state flow test was accomplished by following the same procedures.

Texture analyser test:

41765 TA-XT plus texture analyser was used for this experiment, the test was prepared by using exponent software, Jellies and films was chosen as a product type from Help and education zone, then determination of bloom strength button was pressed, the spindle was moved down to penetrate the sample surface by press on TA- Run to measure the force, the distance, the time, the maximum force to penetrate the sample is determined by bloom strength, while the adhesion is measured when the spindle moved up to determine how sticky the sample is, the test was done triplicate to different site on the sample surface, and the sample results were saved.

 

 

3. Results:

Preparation of Jelly by dispersing 1.5% of sodium alginate 1740 in 10 mL of deionised water and calcium chloride dispersed in another beaker contained 10 mL of deionised water and then mixing both together by adding CaCl solution to sodium alginate beaker.

 

The experiment reveals that using of 1.5% of sodium alginate 5450 takes more than one hour to disperse in 10 mL of water, as well as sodium alginate 8223 which takes more than 40 min, for that reason sodium alginate 1740 type has been chosen for all this experiment steps, moreover the weight of jelly formed decrease with increase of CaCl concentration, while an increment in water remain volume occurred with CaCl concentration raise, correspondingly with an increment of performed jelly cohesiveness.

Experiment No.	Content concentrations with adding 10 mL of deionised water for both of them	Na alginate 1740 hydration time	Weigh of jelly formed	Water remain	Visual characteristics	Visual appearance
1	Na alginate 1.5% Ca Cl 0.3%	7:30 min	16.806 gm	0.5 mL	Standard gel, transparent, quivers, light	Not uniform, not cohesive
2	Na alginate 1.5% Ca Cl 0.5%	9 min	13.561 gm	4.3 mL	Standard gel, transparent, hold it shape, tough	Not uniform, not cohesive
3	Na alginate 1.5% Ca Cl 1%	7:30 min	10.919 gm	6.20 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
4	Na alginate 1.5% Ca Cl 1.5%	7 min	12.142 gm	6.60 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
5	Na alginate 1.5% Ca Cl 2%	4:30 min	11.516 gm	6.80 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
6	Na alginate 1.5% Ca Cl 2.5%	6:30 min	11.620 gm	7.20 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
7	Na alginate 1.5% Ca Cl 5%	7 min	11.103 gm	7.80 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
8	Na alginate 1.5% Ca Cl 10%	7 min	11.863 gm	8.20 mL	Standard gel, transparent, hold it shape, tough	Not uniform, smooth surface
9	Na alginate 1.5% Ca Cl 15%	7 min	11.476 gm	8.50 mL	Standard gel, transparent, hold it shape, tough	Uniform, smooth surface
10	Na alginate 1.5% Ca Cl 20%	6:30 min	9.146 gm	11 mL	Standard gel, transparent, hold it shape, tough	Uniform, smooth surface

Preparation of Jelly by dispersing 1.5% of sodium alginate 1740 in 15 mL of deionised water and calcium chloride dispersed in another beaker contained 5 mL of deionised water and mixing both together.

 

Experiment No.	Content concentrations with adding 15 mL of deionised water to Na alginate, 5 mL to Ca Cl	Na alginate 1740 hydration time	Weigh of jelly formed	Water remain	Visual characteristics	Visual appearance
1	Na alginate 1.5% Ca Cl 0.3%	7 min	9.747 gm	7 mL	Hard jelly, transparent, light, hold it shape	Not uniform, Not cohesive
2	Na alginate 1.5% Ca Cl 0.5%	3 min	15.160 gm	7 mL	Hard jelly, transparent, tough, hold it shape	Not uniform, Not cohesive
3	Na alginate 1.5% Ca Cl 1%	7 min	12.880 gm	2.60 mL	Hard jelly, transparent, tough, hold it shape	Uniform, cohesive
4	Na alginate 1.5% Ca Cl 1.5%	4 min	13.788 gm	2.60 mL	Hard jelly, transparent, tough, hold it shape	Uniform, cohesive
5	Na alginate 1.5% Ca Cl 2%	4 min	13.528 gm	4.60 mL	Hard jelly, transparent, tough, hold it shape	Uniform, cohesive
6	Na alginate 1.5% Ca Cl 2.5%	7 min	14.670 gm	3.60 mL	Hard jelly, transparent, tough, hold it shape	Uniform, cohesive
7	Na alginate 1.5% Ca Cl 5%	7:30 min	15.053 gm	3 mL	Hard jelly, transparent, tough, hold it shape	Uniform, cohesive
8	Na alginate 1.5% Ca Cl 10%	4 min	13.935 gm	5.40 mL	Hard jelly, transparent, tough, hold it shape	Not uniform, smooth surface
9	Na alginate 1.5% Ca Cl 15%	7:30 min	13.680 gm	6.40 mL	Hard jelly, transparent, tough, hold it shape	Uniform, smooth surface
10	Na alginate 1.5% Ca Cl 20%	4 min	13.019 gm	6.60 mL	Hard jelly, transparent, tough, hold it shape	Uniform, smooth surface

 

From the results shown above, there are inconsistency in the results given for weigh of jelly formed and water remain volume according to the increase of CaCl concentration, the variation in this result it’s not compatible with the result in the preceding experiment, for this reason this approach has been ignored.

 

 

Preparation of Jelly by dispersing 1 % of sodium alginate 1740 in 10 mL of deionised water and calcium chloride dispersed in another beaker contained 10 mL of deionised water and mixing both together by adding CaCl to sodium alginate beaker.

Experiment No.	Content concentrations with adding 10 mL of deionised water for both of them	Na alginate 1740 hydration time	Weigh of jelly formed	Water remain	Visual characteristics	Visual appearance
1	Na alginate 1% Ca Cl 0.3%	12 min	11.115 gm	5 mL	Standard gel, transparent, quivers, light	Not uniform, not cohesive
2	Na alginate 1% Ca Cl 0.5%	9 min	11.320 gm	6 mL	Standard gel, transparent, light, quiver	Not uniform, not cohesive
3	Na alginate 1% Ca Cl 1%	7 min	9.260 gm	8 mL	Standard gel, transparent, hold it shape, tough	Not uniform, cohesive
4	Na alginate 1% Ca Cl 1.5%	4 min	10.415 gm	5 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
5	Na alginate 1% Ca Cl 2%	6 min	9919 gm	8 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
6	Na alginate 1% Ca Cl 2.5%	16 min	10.330 gm	7.20 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
7	Na alginate 1% Ca Cl 5%	7 min	11.123 gm	7 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
8	Na alginate 1% Ca Cl 10%	10 min	9.767 gm	9 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
9	Na alginate 1% Ca Cl 15%	6 min	8.868 gm	8.20 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive
10	Na alginate 1% Ca Cl 20%	15 min	11.048 gm	8 mL	Standard gel, transparent, hold it shape, tough	Uniform, cohesive

 

 

Similarly, the cohesiveness and toughness of the performed jelly increase with an increase of CaCl2 concentration, from the results shown above it appears that both Na alginate 1% CaCl2 0.5% and Na alginate 1% CaCl2 1% have a proper jelly characteristics comparing to other formulations, therefore both formulations could be useful choice for further jelly enchantment procedures.

This table illustrate the hydration time of different materials in present of 20 mL deionised water, and whether the hydration time retards or improved by adding another materials.

 

 

Material name 1% in present of 20 mL deionised water		Hydration time	Formed material	With sucrose 1%	With sucrose 2%	With Ca sulphate	With Ca chloride	With Ca carbonate	With Maltodextrin	With Tween 80	With Glycerol
Lycatab pgs		30 sec	Turbid fluid	1 min, white turbid fluid	2 min, white turbid fluid	30 sec	20 sec, Turbid fluid	1 min, white turbid fluid	3 min, white turbid fluid	30 sec, white turbid fluid	30 sec, turbid fluid
Maize starch		1 min	Turbid fluid	30 sec, Turbid fluid	6 min, Turbid fluid	2 min, Turbid fluid	30 sec, Turbid fluid	40 sec, white turbid fluid	21 min, Turbid fluid	1 min, White turbid fluid	15 sec, White turbid fluid
Perfeglo starch		8 min	Turbid fluid	11:30 min, White turbid fluid	4 min, White turbid fluid	1:30 min, turbid fluid	14 min, Turbid fluid	5 min, separation occured	3 min, turbid fluid	3 min, White turbid fluid	5 min, White turbid fluid
HPMC		9 min	Transparent fluid	14 min, transparent fluid	25 min, transparent fluid	15 min, turbid fluid	4 min, transparent fluid	15 min, white turbid fluid	30 min, White turbid fluid	19 min, transparent fluid	10 min, transparent fluid
Polyethylene Oxide		14 min	Turbid fluid	15 min, transparent fluid	23 min, turbid fluid	20 min, turbid fluid	7 min, Turbid fluid	8 min, white turbid fluid	1:42 min turbid fluid, poor hydration	7 min, White turbid fluid	6 min, slightly turbid fluid
HM Pectin		26 min	Turbid fluid	28 min, turbid fluid	22 min, turbid fluid	7:30 min, turbid fluid	18 min, Turbid fluid	12 min, turbid thickened fluid	24 min, turbid fluid	13 min, turbid fluid	20 min, turbid fluid
LM Pectin		20 min	Turbid fluid	22 min, turbid fluid	32 min, turbid fluid	2 min, turbid fluid	4 min, Turbid fluid	15 min, turbid thickened fluid	13 min, turbid fluid	46 min, turbid fluid	6 min, turbid thickened fluid
Carbopol		120 min	Transparent thickened fluid	3:35 min, transparent thickened fluid	1:30 min, turbid thickened fluid	13 min, turbid fluid	14 min, Turbid fluid	Over one hour,  turbid thickened fluid	1:11 min, turbid thickened fluid	19 min, turbid thickened fluid	42 min, turbid thickened fluid
Egg protein		1:30 min	Turbid fluid with residual filament	3 h, residual filament	5 h, residual filament	12 min, turbid fluid	6 min, Turbid fluid	5 min, white turbid fluid	50min,turbid fluid with small remain powder	5 min, turbid fluid	5 min, turbid fluid
High gellan gum 0.3%		45 min	Turbid thickened fluid	48 min, thickened fluid	56 min, turbid thickened fluid	1% con, 2 min, turbid fluid	5 min, Turbid fluid	16 min, turbid thickened fluid	8 min, white thickened fluid	???, turbid thickened fluid	39 min, turbid thickened fluid
Low gellan gum		20 sec	Transparent thickened fluid	40 sec, thickened fluid	60 sec, turbid thickened fluid	2 min, turbid fluid	5 min, Turbid fluid	13 min, turbid thickened fluid	21 min, turbid thickened fluid	1 min, turbid thickened fluid	3 min, turbid thickened fluid
Gum Karaya		11 min	Transparent thickened fluid	14 min, Transparent thickened fluid	14 min, turbid thickned fluid	19 min, turbid fluid	16 min, Turbid fluid	21 min, turbid thickened fluid	10 min, turbid thickened fluid	23 min, turbid thickened fluid	7 min, turbid thickened fluid
Gum tracaganth		1:08 min	turbid thickened fluid	2:30 min, turbid thickened fluid	2:30 min, turbid thickened fluid	22 min, turbid thickened fluid	26 min, Turbid fluid	33 min, turbid thickened fluid	1:11 min, turbid thickened fluid	59 min, turbid thickened fluid	41 min, turbid thickened fluid
Guar Gum		2 min	turbid thickened fluid	30 sec, turbid thickened fluid	1 min, turbid thickened fluid	1 min, turbid fluid	2 min, turbid thickened fluid	30 sec, turbid thickened fluid	11 min, turbid thickened fluid	1 min, turbid fluid	2 min, turbid thickened fluid
Arabic Gum		18 min	Transparent fluid	17 min, transparent fluid	13 min, transparent fluid	8 min, white turbid fluid	4 min, transparent fluid	6 min, white turbid fluid	7 min, transparent fluid	6 min, transparent fluid	5 min, transparent fluid
Xanthan Gum		14 min	Transparent thickened fluid	48 min, turbid thickened fluid	1:09 min, turbid thickened fluid	22 min, turbid thickened fluid	Over one hour, turbid thickened fluid	60 min, turbid thickened fluid	1:07 min, turbid thickened fluid	45 min, turbid thickened fluid	Over one hour, turbid thickened fluid
Locust bean Gum		30 min	Transparent thickened fluid	1:40 min, turbid thickened fluid	3:15 min, turbid thickened fluid	1:15 min, turbid slightly thickened fluid	Over one hour, turbid slightly thickened fluid	Over one hour, turbid thickened fluid	2:20 min, turbid thickened fluid, poor hydration, remaining powder	20 min, turbid fluid	Over one hour, turbid fluid
Iota carrageenan		37 min	Transparent fluid	58 min, Transparent fluid	57 min, Transparent fluid	7 min, white turbid fluid	1 min, white turbid fluid	Over one hour, turbid thickened fluid	45 min, turbid thickened fluid	20 min, Transparent thickened fluid	20 min, Transparent thickened fluid
Kappa carrageenan	20 min		Transparent thickened fluid	48 min, turbid thickened fluid	1:34 min, turbid thickened fluid	3 min, turbid fluid	1 min, turbid fluid	32 min, turbid thickened fluid	1:07 min, turbid thickened fluid	50 min, turbid thickened fluid	Over one hour, turbid thickened fluid
Lamda carrageenan		21 min	Transparent thickened fluid	39 min, Transparent thickened fluid	42 min, Transparent thickened fluid	30 min, white turbid fluid	58 min, turbid slightly thickened fluid	28 min, turbid thickened fluid	12 min, turbid thickened fluid	21 min, turbid thickened fluid	18 min, turbid thickened fluid
Cekol 2000		56 min	Transparent thickened fluid	1:52 min, Transparent thickened fluid	3:20 min, thickened fluid, formed lump	2:30 min, turbid thickened fluid, formed lump	Over one hour, turbid slightly thickened fluid	Over one hour, turbid thickened fluid	30 min, turbid thickened fluid	38 min, Transparent thickened fluid	20 min, turbid thickened fluid

 

 

The purpose of doing this piece of work it’s to identify the hydration time of each material in water, and to define the formed material, and which additive factors could retard or accelerate the hydration rate, from the results shown above some material formed thickened fluid but it takes long time to dissolve in water, given this, the additives which accelerate their hydration rate could be a convenient choice for them, whereas the additives which prolong the hydration rate would be disregarded, in essence faster dissolving gelling material could be a useful choice for making an instant jelly.

 

 

 

 

 

 

 

 

 

This table shown the material yielded a thickened fluid in a reasonable amount of time

 

Material name 1% in present of 20 mL deionised water	Hydration time	Formed material
HM Pectin	12 min, with Ca carbonate	Turbid thickened fluid
LM Pectin	6 min, with Glycerol	Turbid thickened fluid
High gellan gum 0.3%	8 min, with maltodextrin	White thickened fluid
Low gellan gum	20 sec, with deionised water	Transparent thickened fluid
Gum Karaya	7 min, with Glycerol	Turbid thickened fluid
Guar Gum	30 sec, with 1% of sucrose	Turbid thickened fluid
Guar Gum	2 min, with deionised water	Turbid thickened fluid
Xanthan Gum	14 min, with deionised water	Transparent thickened fluid
L- carrageenan	12 min, with maltodextrin	Turbid thickened fluid

 

It has noticed that Low gellan gum is dissolved rapidly in deionise water and formed thickened fluid

Jelly Development experiment:

Preparation of jelly by adding a new material to sodium alginate 1%, CaCl 1% and by using

75% of sodium alginate: new material 25%

25% of sodium alginate: new material 75%

Compare the different between adding the new material once to Na alginate and then to CaCl as a second method.

 

 

Na alginate1%, Pectin1%,   CaCl 1%	Na alginate1%, CaCl 1%, Pectin1%	Na alginate1.5%, Pectin0.5%, CaCl 1%	Na alginate0.5%, Pectin1.5%, CaCl 1%
Yellow jelly, uniform, cohesive, tough	The hydration time was within 10 sec, uniform cohesive yellow jelly, tough	Pectin was added to CaCl, jelly, not cohesive, easy to cut, quiver	Pectin was added to CaCl, agglomerated thickened yellow fluid
Na alginate1%,Guar gum1%, CaCl 1%	Na alginate1%, Guar gum 1%, CaCl 1%	Na alginate1.5%, Guar gum 0.5%, CaCl 1%	Na alginate 0.5%, Guar gum 1.5%, CaCl 1%
Turbid jelly, cohesive, uniform, wobbly	Form thickened fluid, thereafter Na alginate added to it, form gel	Jelly, not uniform, not cohesive, quiver	Poor hydration, form gel
Na alginate1%,K cargnan1%, CaCl 1%	Na alginate1%,              K cargnan1%, CaCl 1%	Na alginate1.5%, K cargnan 0.5%, CaCl 1%	Na alginate 0.5%,  K cargnan1.5%, CaCl 1%
Poor hydration	Dissolve faster, formed jelly, neither cohesive nor quiver	Jelly, uniform, cohesive, wobbly.	Formed gel
Na alginate1%, Xanthn gum1%, CaCl 1%	Na alginate1%, Xanthn gum1%, CaCl 1%	Na alginate1.5%, Xanthn gum 0.5%, CaCl 1%	Na alginate 0.5%, Xanthn gum 1.5%, CaCl 1%
Jelly, turbid, uniform, cohesive, tough	Poor hydration forms lump	Jelly, not uniform, not cohesive, not wobble	Jelly, cohesive, uniform, quiver
Na alginate1%, Arabic gum1%, CaCl 1%	Na alginate1%, Arabic gum1%, CaCl 1%	Na alginate1.5%, Arabic gum 0.5%, CaCl 1%	Na alginate 0.5%, Arabic gum 1.5%, CaCl 1%
Uniform jelly, not cohesive, easy to cut, not quiver	Jelly, quiver, neither uniform nor cohesive	Uniform jelly, cohesive, tough, hold it shape	Small portion of jelly, neither uniform nor cohesive, not quiver
Na alginate1%, gum karaya1%, CaCl 1%	Na alginate1%, gum karaya 1%, CaCl 1%	Na alginate1.5%, gum karaya 0.5%, CaCl 1%	Na alginate 0.5%, gum karaya 1.5%, CaCl 1%
Takes long time to dissolve, jelly, cohesive, uniform, wobbly	Dissolve faster, jelly, neither uniform nor cohesive, wobbly	By using hot plate, uniform jelly, cohesive, slightly quiver and rigid	Although by using hot plate it doesn’t dissolve properly in Na alginate.
Na alginate1%, gum tragacaganth 1%, CaCl 1%	Na alginate1%, CaCl 1%, gum tragacaganth 1%	Na alginate1.5%, gum tragacaganth 0.5%, CaCl 1%	Na alginate 0.5%, gum tragacaganth 1.5%, CaCl 1%
Takes long time to dissolve, jelly, cohesive, uniform, hold it shape, easy to cut by spatula	Dissolve faster, jelly, neither uniform nor cohesive, wobbly	Jelly, cohesive, uniform, hold it shape, tough	Forms thickened fluid, Na alginate was added to it.
Na alginate1%, maize starch 1%, CaCl 1%	Na alginate1%, CaCl 1%, maize starch 1%	Na alginate1.5%, maize starch 0.5%, CaCl 1%	Na alginate 0.5%, maize starch 1.5%, CaCl 1%
Jelly, cohesive, uniform, hold it shape, easy to cut by spatula	Jelly, cohesive, not uniform, hold it shape, tough	Jelly, cohesive, not uniform, hold it shape, tough	Jelly, neither uniform nor cohesive, not quiver
Na alginate1%, Polthl ox 1%, CaCl 1%	Na alginate1%, CaCl 1%, Polthl ox 1%	Na alginate1.5%, Polthl ox 0.5%, CaCl 1%	Na alginate 0.5%, Polthl ox 1.5%, CaCl 1%
Jelly, cohesive, uniform, wobbly	Jelly, cohesive, uniform, hold it shape, tough	Jelly, cohesive, uniform, hold it shape, tough	Jelly, neither uniform nor cohesive, hold it shape
Na alginate1%, Carbopol 1%, CaCl 1%	Na alginate1%, CaCl 1%, Carbopol 1%	Na alginate1.5%, Carbopol 0.5%, CaCl 1%	Na alginate 0.5%, Carbopol 1.5%, CaCl 1%
Jelly, cohesive, uniform, wobbly	Jelly, cohesive, uniform, hold it shape, easy to cut.	Jelly, cohesive, uniform, hold it shape, tough	Takes long time to dissolve, formed gel.
Na alginate1%, HPMC 1%, CaCl 1%	Na alginate1%, CaCl 1%, HPMC 1%	Na alginate1.5%, HPMC 0.5%, CaCl 1%	Na alginate 0.5%, HPMC 1.5%, CaCl 1%
Jelly, cohesive, not uniform, hold it shape, easy to cut.	Jelly, cohesive, not uniform, slightly quiver, easy to cut.	Jelly, cohesive, uniform, hold it shape, tough	Formed small portion of jelly, neither uniform nor cohesive, easy to cut, not quiver
Na alginate1%, Egg protein 1%, CaCl 1%	Na alginate1%, CaCl 1%, Egg protein 1%	Na alginate1.5%, Egg protein 0.5%, CaCl 1%	Na alginate 0.5%, Egg protein 1.5%, CaCl 1%
Jelly, cohesive, not uniform, hold it shape, tough.	Takes long time to dissolve, jelly, cohesive, uniform, hold it shape	Jelly, cohesive, uniform, hold it shape, tough	Jelly, neither uniform nor cohesive, easy to cut, not quiver
Na alginate1%, Cekol 1%,    CaCl 1%	Na alginate1%, CaCl 1%, Cekol 1%	Na alginate1.5%, Cekol 0.5%, CaCl 1%	Na alginate 0.5%, Cekol 1.5%, CaCl 1%
Jelly, cohesive, uniform, wobbly	Takes long time to dissolve, thickened fluid.	Jelly, cohesive, not uniform, slightly quiver, easy to cut.	Doesn’t dissolve properly
Na alginate1%, LBG 1%, CaCl 1%	Na alginate1%, CaCl 1%, LBG 1%	Na alginate1.5%, LBG 0.5%, CaCl 1%	Na alginate 0.5%, LBG 1.5%, CaCl 1%
Small portion of jelly, cohesive, not uniform, slightly quiver.	Doesn’t dissolve properly	Jelly, cohesive, uniform, hold it shape, tough	Doesn’t dissolve properly
Na alginate1%, LAGG 1%, CaCl 1%	Na alginate1%, CaCl 1%, LAGG 1%	Na alginate1.5%, LAGG 0.5%, CaCl 1%	Na alginate 0.5%, LAGG 1.5%, CaCl 1%
Jelly, cohesive, uniform, slightly quiver	Jelly, cohesive, uniform, wobbly	Jelly, cohesive, uniform, hold it shape.	Jelly, cohesive, not uniform, wobbly
Na alginate1%, Perfeglo 1%, CaCl 1%	Na alginate1%, CaCl 1%, Perfeglo 1%	Na alginate 1.5%, Perfeglo 0.5%, CaCl 1%	Na alginate 0.5%, Perfeglo 1.5%, CaCl 1%
Jelly, cohesive, uniform, wobbly	Takes long time to dissolve, jelly, cohesive, uniform, slightly quiver	Takes long time to dissolve, jelly, neither uniform nor cohesive, quiver	Doesn’t dissolve properly

Afterwards, the formulations showing promise features such as wobbly jelly were prepared again to identify their properties then differentiate between them to pick up the finest formulation for further characterisation assessment, while other formulation has been neglected because it formed either rigid jelly which can be problematic for dysphagic patients or thickened fluid which can be stick in mouth and throat.

 

The table shows the finest formulations figured out from jelly development procedures

Experiment No.	Content concentrations with adding 10 mL of deionised water for both of them	Na alginate 1740 Hydration time	Weigh of jelly formed	Water remain	Visual characteristics	Visual appearance
1	Na alginate 1%, Guar gum 1% Ca Cl 1%	4 min	10.160 gm	9 mL	Jelly, Quiver	Uniform, cohesive, smooth surface
2	Na alginate1.5%, K crgnen 0.5% Ca Cl 1%	More than 10 min	9.690 gm	8 mL	Jelly, Quiver	Uniform, not very cohesive, wavy surface
3	Na alginate0.5%, Xnthn gum 1.5% Ca Cl 1%	More than 10 min	11.565 gm	7 mL	Jelly, Quiver	Uniform, cohesive, smooth surface
4	Na alginate 1%, Gum karaya 1% Ca Cl 1%	More than 10 min	10.003 gm	8.20 mL	Jelly, Quiver	Not uniform, cohesive, smooth surface
5	Na alginate 1%, polthln ox 1% Ca Cl 1%	7 min	9.970 gm	8 mL	Jelly, Quiver	Uniform, not very cohesive, smooth surface.
6	Na alginate 1%, Carbopol 1% Ca Cl 1%	More than 10 min	10.550 gm	8 mL	Jelly, Quiver	Uniform, cohesive, wavy surface
7	Na alginate 1%, Cekol 1% Ca Cl 1%	More than 10 min	10.730 gm	8.20 mL	Jelly, Quiver	Uniform, cohesive, smooth surface
8	Na alginate 1% Ca Cl 1%, LAGG 1%	4 min	10.940 gm	6 mL	Jelly, Quiver	Uniform, not very cohesive, wavy surface.
9	Na alginate 1%, Perfeglo 1% Ca Cl 1%	7 min	11.176 gm	7 mL	Jelly, Quiver	Uniform, not very cohesive, wavy surface.

 

 

 

 

Thereafter formulation 8.Na alginate 1%, CaCl 1%, low gellan gum 1%, and 9. Na alginate 1%, perfeglo starch 1% formulation are considered as the best two formulations from them due to it takes less time to dissolve in water, it formed less water volume, and their characteristic and visual appearance is much more better than other preparation, therefore they picked up to assess their characterisation by using rheometer and texture analyser, then compare their result with Hartley’s ready-made jelly.

 

 

Hartley’s ready-made jelly.

 

Characteristics assessment by using rheometer TA instrument AR1500ex + Julabo AWC100 cooling system

 

Stress sweep test

Frequency sweep test

Steady state flow sweep test

 

 

 

 

 

 

Hartley’s Jelly prepared in the lab by using heating process

 

 

 

Characteristics assessment by using rheometer TA instrument AR1500ex + Julabo AWC100 cooling system

 

Stress sweep test

 

Frequency sweep test

 

Steady state flow sweep test

 

 

 

 

 

 

Lab prepared jelly

 

1. Na alginate 1%,CaCl 1%, low gellan gum 1%

 

 

Characteristics assessment by using rheometer TA instrument AR1500ex + Julabo AWC100 cooling system

 

 

Stress sweep test

 

Frequency sweep test

 

Steady state flow step

 

 

 

 

 

 

2. Na alginate 1%, perfeglo starch 1%, CaCl 1%

 

 

Characteristics assessment by using rheometer TA instrument AR1500ex + Julabo AWC100 cooling system

 

 

Stress sweep test

 

Frequency sweep test

 

Steady state flow step

 

 

Texture analyser result:

 

Commercial Jelly Hartley’s prepared by heating process

	Bloom strength g	Adhesion g
Sample no.1	13.494	-1.472
Sample no.2	17.645	-1.147
Sample no.3	12.069	-0.809
Sample no.4	15.895	-1.219
Average	14.776	-1.162
S.D.	2.148	0.237
C.V.	14.528	-20.404

 

 

 

Na alginate 1%, CaCl 1%, low gellan gum 1%.

	Bloom strength g	Adhesion g
Sample no.1	220.278	-102.083
Sample no.2	220.278	-102.083
Sample no.3	220.278	-102.083
Average	220.278	-102.083
S.D.	0	0
C.V.

 

 

 

Na alginate 1%, perfeglo starch 1%, CaCl 1%.

 

	Bloom strength g	Adhesion g
Sample no.1	122.61	-6.381
Sample no.2	137.71	-1.255
Sample no.3	132.62	-0.628
Average	130.98	-2.905
S.D.	6.27	2.788
C.V.	4.79	-95.993

 

4. Discussion:

Sodium alginate and calcium chloride for jelly preparation:

Alginate (Polysaccharide) is considered as one of the most hydrocolloids used for thickening and gelling material applied in foods, since it’s mainly present in cell wall and intracellular species of brown algae, numerous sorts of alginate has been developed for commercial uses in drugs and foods and each kind of alginates has its own properties depends on their chemical nature, therefore the intended application of alginates either for thickening or gel forming determines which kind of alginates have to be choose, in this prospective alginic acid which is the acidic form of the alginates has been converted commercially by incorporating salt to becomes water soluble product such as: sodium alginate, magnesium alginate, potassium alginate and many others, basically, the formation process of gel attained through the interaction between sodium alginate and cations like calcium ions , the divalent cations cross link the alginate poly anionic molecules to perform gel network in any temperature degree, thermo- irreversibility  is the main advantage of these formulations because such property may enable maintain their shape and physical characteristics during heating or cooling when restoring, in particular this attribute could be valuable when use this gel or jelly  as a drug vehicle because such formulations would be stable throughout different conditions of manufacturing process, in contrast thermos-reversible jelly can be prepared in acidic media like 3.4 pH by used sodium alginate and high- methoxyl pectin (Onsøyen, E., 1997), however, alginates couldn’t exert viscosity to the solution in alkaline media precisely over the range of pH 5-11, while the electrostatic repulsion diminished between alginates chains in result of protonation of free –COO- ions to –COOH and formation of hydrogen bond in pH below 5, thus produce higher viscosities, progressively, the gel will form when pH is reduced further, commonly between pH 3-4, apart from this gelation may occurred if alginates contains residual calcium in about pH 5 (King, 1983), furthermore, the viscosity of alginate solution is increased with presence of low concentrations of calcium ions, in this context, the propensity of making gel in increased with increased calcium concentrations, the divalent ion of calcium have the ability to displace the hydrogen ions on the carboxylic acid groups of adjacent chains in alginates and formed simple ionic bridges between the chains, essentially, calcium assist hold alginates molecules together and involve alpha- L guluronic acid, therefore the higher proportion of calcium ions will provide greater gel strength (McHugh, 1987), in essence, the ultimate aim of this study it’s to attain a jelly formulation able to exert sustain release of their loading drug, In this prospective (El-Kamel, et al, 2010) observe that diltiazem  HCl (DTZ) can be loaded in alginate beads by gelation techniques, the drug loading could be achieved with 88% absolute bioavailability  through a mixture comprising of  0.8% methylcellulose (MC) and 4% alginate cured in 2% calcium chloride, The in vitro release of DTZ from MC-alginate beads displayed an extended release design comparing with commercially available sustained-release (Dilzem1 SR).

 

 

Gelling material hydration time test:

In this framework, the solubility of several gelling material have been examined, the purpose of doing this experiment it’s to identify the formed material of each sample and the time consumed for dissolving in water and which additive factors could enhance or retard the solubility rate, in order to determine proper ingredients for preparing an instant jelly, in essence, the particle type and their size play a key role in hydration process, for instance: sodium alginate powders form a sticky surface on water solution unless other efficient precautions are applied, the powders are promptly stick together to form clumps which are very slow to entirely hydrate in water, in this regard, coarse powder have preference since it’s easy to disperse and being separate in water while they take long time to dissolve unlike the fine powders, the fine powders have the property of  dissolving rapidly but the demerits with this type is the incidence of forming clump its usually occurred, the risk could be decreased with mixing sodium alginate powders with sugar, moreover alginates powder contain fibrous particles dissolve more quickly than the one who have granular particles, however fibrous particles have more tendency to fold around each other and this property delay the disperse rate of this particles (McHugh, 1987).

Furthermore, Sodium alginate has struggle to dissolve in water if the water holds compounds compete them for hydration such as: sugar, starch, protein, salts, and calcium ions, Acidic solutions also hinder alginates powder hydration especially if the pH is lower than 4.0, using of propylene glycol alginate could be an ideal solution to resolve this difficulty which allow powder hydration down to around pH 2 (McHugh, 1987).

 

(Brandelero, et al 2010) explained that Using of tween 80 as a surfactant increased the free volume among the starch chains, thus, aiding the diffusion of water vapor then enhance the hydration rate, and this thing appeared evidently in the result experiment when adding tween 80 with perfeglo starch, whereas (Sansone, et al 2011) point out that The Maltodextrin/Pectin matrix has the ability to cover the unlikable odor of the extracts and the product is promptly dissolve in water, and this feature is effectual for making jelly with a pleasant smell, in another case, adding of glycerol has increased solubility of various gelling material and correspondingly enhance the protein’s solubility and that’s appeared in the experiment with egg protein, the protein/protein interactions come to be more repulsive as glycerol is augmented (Farnum, et al, 1999), using of divalent cations such as: calcium chloride, calcium sulphate, calcium carbonate could attained gelation in solution having deionised water, the impact of these salts contain ions is allowing these that’s ions to diffuse through gallen gum solution or by release within gallen gum, from the experiment results it’s obvious that introducing of these cations accomplish gelation in thickened fluid with improved the hydration time with high acyl gellan gum (Baird, shim 1985)

 

Jelly development:

Various materials have been added in order to refine jelly prepared by using sodium alginate and calcium chloride powders, the results have shown that adding of some of those materials has improved jelly characterises comparing to the former jelly, ideally, low acyl gellan gum and perfeglo starch have a significant enhancement results, Gellan gum is a linear anionic polysaccharide which form a three-fold double-helical structure in suitable aqueous media, The aggregation of double-helical segments leads to a three-dimensional network , Ca⁺⁺ divalent cations could stabilize the gellan three-dimensional network through direct cross linking, the capability of gels to preserve water in their structure which is generally expressed by water holding capacity (WHC) contribute to the formation the main characteristics of gels,. WHC of the gel is determined by the gelation mechanism, and it’s an essential quality factor for the gels due to their impacts on textural properties (Huang, et al, 2003). Intrinsically, Gellan gum has the ability to yield easy-to-swallow attribute to gels and various solid dosage form, and to provide sustained release of many drugs and besides it can be used for microcapsules and microparticles preparation, hence, nano or microparticles can be prepared by ionotropic gelation method, through  a mixture of polysaccharide comprises of alginate, gellan and pectin and these can be dissolved in water or chitosan in acidic media, then this solutions could be dropped under stirring to solutions containing other counterions,  thereafter various therapeutic agents can be loaded into them  to achieve sustain release property (Racoviţă, et al, 2009), similarly, the other jelly formulation containing perfeglo starch can follow the same approach to achieve similar purposes, pregelatinized sweet potato flour could be blended with controlled release alginate microbeads by using ionotropic gelation method (Jha, A.K. and Bhattacharya, A, 2008)

 

Prepared jelly rheometer result:

1. Na alginate 1%,CaCl 1%, low gellan gum 1%.

The stress sweep test result has shown red graph G prime which is indicated to the energy stored in the sample, and it illustrate their elasticity under applying force, while the blue graph G double prime illustrate how much energy is loss, from the results it appears that G prime the red graph is above the blue one, which means that the formulation is jelly and that’s conform with commercial jelly results, however the commercial jelly configuration is deformed under less force comparing to the lab prepared jelly, and that’s imply that the lab prepared jelly is slightly cohesive than commercial jelly.

2. Na alginate 1%, perfeglo starch 1%, CaCl 1%.

Similarly, from the stress sweep test result, it figured out that the red graph G prime is above the blue graph G double prime, which meant that the formulation is jelly, however both graphs entails and they didn’t deformed under applying force, which suggest that the formulation is much cohesive comparing to the commercial jelly.

Prepared jelly texture analyser result:

1. Na alginate 1%,CaCl 1%, low gellan gum 1%.

 

 

 

 

 

 

1. Na alginate 1%,CaCl 1%, low gellan gum 1%.

 

 

 

 

 

 

 

 

 

 

 

 

 

Conclusion:

In conclusion, the project has demonstrated the functions of modified release formulation drug delivery system and their effects on the body. In addition to it suggests jelly formulation where the active ingredient of the drug can ultimately loaded into them, such formulations can exhibit sustain release drug property and facilitate drug administration for dysphagic patients, which might increase patient compliance, provide much safety, and maximize the utility of the prescribed medicine through better control of chronic disease status such as: hypertension and diabetes, a mixture comprising of alginate and calcium chloride can achieve instant jelly and it can be used as a drug vehicle where the drug can be loaded in alginates via gelation technique, UV spectrophotometry could predict whether the drug has been successfully loaded into these formulations or not, The influence of the mixture on the drug properties such as drug bioavailability, and drug release, plasma concentration, and correlation between in vitro and in vivo release have to be examined (Yamada et al, 2001), additional test would be done to ascertained that these formulation achieve their purpose, in vitro experiment by using an artificial throat can be testify whether these formulation passing smoothly through the throat or not, The estimated result is that jelly formulations demonstrated above are easily swallowing and supply a steady state plasma level of loaded drug.

 

 

 

 

 

References

 

1. Baird, J.K. and Shim, J.L., Merck & Co., Inc., 1985. Non-heated gellan gum gels. U.S. Patent 4,503,084.
2. Brandelero, R.P.H., Yamashita, F. and Grossmann, M.V.E., 2010. The effect of surfactant Tween 80 on the hydrophilicity, water vapor permeation, and the mechanical properties of cassava starch and poly (butylene adipate-co-terephthalate)(PBAT) blend films. Carbohydrate Polymers, 82(4), pp.1102-1109.
3. Cherukuri, S.R., 2012. Rapid Melt Controlled Release Taste-Masked Compositions. U.S. Patent Application 13/589,101.
4. Cornish, P., 2005. “Avoid the crush”: hazards of medication administration in patients with dysphagia or a feeding tube. Canadian Medical Association Journal, 172(7), pp.871-872.
5. Dixit, N., Maurya, S.D. and Sagar, B.P., 2013. Sustained release drug delivery system. Indian Journal of Research in Pharmacy and Biotechnology, 1(3), p.305.
6. El-Kamel, A.H., Al-Gohary, O.M.N. and Hosny, E.A., 2010. Alginate-diltiazem hydrochloride beads: optimization of formulation factors, in vitro and in vivo availability. Journal of microencapsulation.
7. Farnum, M. and Zukoski, C., 1999. Effect of glycerol on the interactions and solubility of bovine pancreatic trypsin inhibitor. Biophysical journal, 76(5), pp.2716-2726
8. Goel, H., Rai, P., Rana, V. and Tiwary, A.K., 2008. Orally disintegrating systems: innovations in formulation and technology. Recent patents on drug delivery & formulation, 2(3), pp.258-274.
9. Grant, J., Hoorens, S., Sivadasan, S., van het Loo, M. and DaVanzo, J., 2004. Low fertility and population ageing: causes consequences and policy options.
10. Hirsh, J., Fleming, A. and Rariy, R., Collegium Pharmaceutical, Inc., 2004. Multiparticulate compositions of milnacipran for oral administration. U.S. Patent Application 10/766,124.
11. Huang, Y., Tang, J., Swanson, B.G. and Rasco, B.A., 2003. Effect of calcium concentration on textural properties of high and low acyl mixed gellan gels. Carbohydrate Polymers, 54(4), pp.517-522.

 

 

12. Ichikawa, H., Fujioka, K., Adeyeye, M.C. and Fukumori, Y., 2001. Use of ion-exchange resins to prepare 100 μm-sized microcapsules with prolonged drug-release by the Wurster process. International journal of pharmaceutics, 216(1), pp.67-76.
13. toh, K., Hatakeyama, T., Shimoyama, T., Miyazaki, S., D’Emanuele, A. and Attwood, D., 2011. In situ gelling formulation based on methylcellulose/pectin system for oral-sustained drug delivery to dysphagic patients. Drug development and industrial pharmacy, 37(7), pp.790-797.
14. Jacob, S. and Shirwaikar, A., 2009. Preparation and evaluation of microencapsulated fast melt tablets of ambroxol hydrochloride. Indian journal of pharmaceutical sciences, 71(3), p.276.
15. Jha, A.K. and Bhattacharya, A., 2008. Name of the paper: preparation and in vito evaluation of sweet potato starch blended sodium alginate microbeads. Advances in Natural and Applied Sciences, 2(3), pp.122-129.
16. Kelly, J., D’Cruz, G. and Wright, D., 2009. A qualitative study of the problems surrounding medicine administration to patients with dysphagia. Dysphagia, 24(1), pp.49-56.
17. King, A.H., 1983. Brown seaweed extracts (alginates). In Food hydrocolloids, edited by M. Glicksman. Boca Raton, Florida, CRC Press, pp.115-88.
18. Maronga, S., 1998. On the optimization of the fluidized bed particulate coating process.
19. McHugh, D.J., 1987. Production, properties and uses of alginates. Production and Utilization of Products from Commercial Seaweeds. FAO. Fish. Tech. Pap, 288, pp.58-115.
20. Mitchell J. Oral dosage forms that should not be crushed: 2008. Available at ismp.org/tools/donotcrush.pdf [accessed May 10, 2008].
21. Mittal, G., Sahana, D.K., Bhardwaj, V. and Kumar, M.R., 2007. Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. Journal of Controlled Release, 119(1), pp.77-85.
22. Miyazaki, S., Takahashi, A., Itoh, K., Ishitani, M., Dairaku, M., Togashi, M., Mikami, R. and Attwood, D., 2009. Preparation and evaluation of gel formulations for oral sustained delivery to dysphagic patients. Drug development and industrial pharmacy, 35(7), pp.780-787.
23. Miyazaki, S., Ishitani, M., Takahashi, A., Shimoyama, T., Itoh, K. and Attwood, D., 2011. Carrageenan gels for oral sustained delivery of acetaminophen to dysphagic patients. Biological and Pharmaceutical Bulletin, 34(1), pp.164-166.
24. Onsøyen, E., 1997. Alginates. In Thickening and gelling agents for food (pp. 22-44). Springer US.
25. Pradesh A, District P. Modified release dosage forms. 2013;6(1):13–21.
26. Prakash, K., Satyanarayana, V., Nagiat, H., Fathi, A., Shanta, A. and Prameela, A., 2014. Formulation development and evaluation of novel oral jellies of carbamazepine using pectin, guar gum, and gellan gum. Asian Journal of Pharmaceutics, p.241.43.
27. Racoviţă, S., Vasiliu, S., Popa, M. and Luca, C., 2009. Polysaccharides based on micro-and nanoparticles obtained by ionic gelation and their applications as drug delivery systems. Revue Roumaine de Chimie, 54(9), pp.709-718.
28. Sansone, F., Mencherini, T., Picerno, P., d’Amore, M., Aquino, R.P. and Lauro, M.R., 2011. Maltodextrin/pectin microparticles by spray drying as carrier for nutraceutical extracts. Journal of Food Engineering, 105(3), pp.468-476.
29. Sastry, S.V., Nyshadham, J.R. and Fix, J.A., 2000. Recent technological advances in oral drug delivery–a review. Pharmaceutical science & technology today, 3(4), pp.138-145.
30. Satyanarayana, D.A. and Keshavarao, K.P., 2014. Novel eatable silk fibroin gels containing salbutamol sulphate for dysphagic and geriatric patients. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm, 6(1).
31. Shimoyama, T., Itoh, K., Kobayashi, M., Miyazaki, S., D’Emanuele, A. and Attwood, D., 2012. Oral liquid in situ gelling methylcellulose/alginate formulations for sustained drug delivery to dysphagic patients. Drug development and industrial pharmacy, 38(8), pp.952-960.
32. Suh, M.K., Kim, H. and Na, D.L., 2009. Dysphagia in patients with dementia: Alzheimer versus vascular. Alzheimer Disease & Associated Disorders, 23(2), pp.178-184.
33. Swamivelmanickam M, Manavalan R, Valliappan K. Mouth Dissolving Tablets: An Overview. Int J Pharm Sci Res [Internet]. 2010;1(12):43–55. Available from: http://www.ugr.es/~adolfina/asignaturas/compdispersables.pdf
34. Weel, K.G., Boelrijk, A.E., Burger, J.J., Verschueren, M., Gruppen, H., Voragen, A.G. and Smit, G., 2004. New device to simulate swallowing and in vivo aroma release in the throat from liquid and semiliquid food systems. Journal of agricultural and food chemistry, 52(21), pp.6564-6571.
35. Xiao, B., Si, X., Zhang, M. and Merlin, D., 2015. Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy. Colloids and Surfaces B: Biointerfaces, 135, pp.379-385.
36. Yamada, T., Onishi, H. and Machida, Y., 2001. Sustained release ketoprofen microparticles with ethylcellulose and carboxymethylethylcellulose. Journal of controlled Release, 75(3), pp.271-282.
37. Zhang, H., Shahbazi, M.A., Mäkilä, E.M., da Silva, T.H., Reis, R.L., Salonen, J.J., Hirvonen, J.T. and Santos, H.A., 2013. Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine. Biomaterials, 34(36), pp.9210-9219.