Title of Invention : SINGLE PACKAGE SYSTEM FOR SOLID

AND LIQUID FOR RECONSTITUTE

[1] Technical Field

[2] The present invention relates to the packing, the equipments and its processes thereof.

[3] The present invention is to provide single packing of solids and liquids of

pharmaceuticals, foods, cosmetics, diagnostics, and laboratory testing devices, reagents for analysis or other allied fields.

[4] In particular, the present invention relates package system to store solids and liquids for in-situ reconstitution in single package, and its processes thereof.

Background Art

[5] Flexible packaging is widely used for various products such as oral care,

cosmetics, personal care, and dietary supplements. These flexible packages are also able to store volatile products. The multi-ply laminations are available to provide stringent barrier properties, or less stringent to be breathable if desired.

[6] The liquid filling machines are available to pack quantitative liquid such as

medicine, beverage, dairy products, health care products, foods, cosmetics and similar liquid products into small flasks, with the unique structure, full function, stable operation and reliable quality.

[7] Solid feeding machines are available to feed precisely the desired quantity of powders, granules, pellets, tablets etc.

[8] The processing machines are also available with roller spreading, forming, filling, end sealing, lot number stamping, end cutting, divided cutting, powder and liquid filling. They are all controlled by computer program along with accuracy with no drop, bubble and spill.

[9] The vials packs are available for single-use with an inverted milliliter graduation on the tube for accurate dispensing. The enclosed product can be preservative- free and contains no bacteriostatic agents maintains sterility and works well after diluting respiratory medication prior to nebulization. [10] The plastic ampoules available which allows single-handed activation. A gentle squeeze, allows contents to be dispensed for applications where the presence of glass is unnecessary, the ampoules are available in a range of sizes, colors, and versions.

[1 1 ] Polypropylene and other packing materials are available which have high

contact clarity, non-blushing, toughness; impact, chemical, solvent and stress crack resistant along with auto-clave stability and low extractability.

Summary of Invention

[12] The present invention comprises of single package (1 1 16) as shown in fig. 1 a which contains at least one backing membrane (444), at least one support membrane (333) at least one interface membrane (222), clump breaking element or guiding vanes (1 1 ) with or without path tubes or notch, or T spindles which are optionally detached or adhered or inbuilt along with interface membrane.

Optionally, the support membrane or backing membrane with opener mode (321 ) containing a notch (654) or path tube (422). The solid material (1 1 1 ) is enclosed between backing membrane and interface. Whereas the liquid (237) is enclosed between support membrane and interface. The interface membrane is required to be broken for reconstitution before usage to convert solid into liquid or semi solid consistency. The breaking of interface is done by pressing at notch (654) of supporting membrane in liquid side. After reconstitution, the prepared liquid or semi solid can be squeezed out through the path (422) at site of usage by pressing support and backing membranes simultaneously after mutilating or modifying the opener (321 ). The path tube is optionally inserted into the body cavities to deliver the reconstituted product directly at the site which is buccal, oral, urethral, nasal, vaginal, rectal or desired site.

[13] The clump breaker (Fig 3a, 3b, 3c) with or without guided vanes (fig 3d,3e, 3f) are having varied shapes which prevents the falling of solid when the backing membrane is tilted to seal, and allows breaking of interface or mixing of solid with liquid. The clump breakers or guided vanes packed along with solid (figure 1 a) or liquid (figure 1 e). [14] The notch mentioned above is present on liquid side (figure 1 a) or on solid side or at the path tube (figure 1 f). The notch is modified as trough (655) as shown in Fig 1 b for better grip and breaking of interface. Fig 1 c shows another modified pit like collapsible notch (656) to assist the old aged patients to break interface.

[15] The opener as mentioned above is present in top or bottom (figure 1 e), front or rear or sideways (Figure 1 d) which is required to be cut or broken or peeled off or pulled to deliver the reconstituted product.

Technical Problem

[16] The materials are stable in solid state during storage, but they are required to be present in liquid state during usage in wet/ /solution/ dispersed/ gel/cream/ semisolid form. The readymade liquid preparations of such materials make them less stable and hence required to be supplied in solid state along with liquid to be used for reconstitution in separate packing.

[17] The approach of use different packages for solid and liquid require measuring and transferring steps or devices which is not effective due to the problem of spillage, lack of precise transfer, contamination and not economic.

Solution to Problem

[18] The present invention provides single pack for both solid and liquid which improves stability during storage and ease of reconstitution during usage makes them versatile with respect to quality of reconstitution with accuracy without spillage; prevention of contamination during transfer; cost effectiveness;

consumer friendly and reduce the load to environment by reducing need of additional accessories for reconstitution and measurement .

Advantageous Effects of Invention

[19] The invention provides package system which is used for many sectors like pharmaceuticals, foods, cosmetics, diagnostics, reagents for testing and accessories or allied fields which require preservation in solid state and consumption as liquid or semisolid state. [20] This invention is used to convert powders, films, granules, sponges or tablets into solutions, dispersions, gels, pastes or semisolids which are more prone to get absorbed at the site of administration in comparison to solids.

[21 ] Administration of solids in form of semisolids or liquids improves the usage by pediatric or geriatric population. These packages can be used in various route of administration like non-invasive which include but not restricted to oral, transmucosal, transdermal, topical and invasive which include parenterals and implants.

[22] The present invention reduces the utilization of packing material by bringing two individual packs to single pack. The separation of solid and liquid for reconstitution improves shelf life and provides the advantages of liquid dosage form by reconstituting it before usage. The reconstitution is done in package itself which is in closed condition, reduce the spillage or contamination.

[23] The present invention provides single package with path tube which can also be inserted into body cavities like oral, buccal, nasal, urethral, vaginal, rectal or desired site to deliver the reconstituted product at site of action. This will further reduce the usage of dispensing accessories to deliver the product at the site.

Brief Description of Drawings

Fig.1

[24] Fig 1 a shows the cut section side view of single unit package where the solid (1 1 1 ) and liquid (237) are separated by interface membrane (222) along with clump breaker (1 1 ). The package encloses solid with backing membrane (333) and liquid with supporting membrane (444). The notch (654) is pressed to break the interface and opening end (321 ) is attached to path tube which is mutilated to deliver the reconstituted preparation.

[25] Fig 1 b is modified unit package with trough like notch (655) to ease the

breaking of interface and better grip.

[26] Fig 1 c is modified unit package with pit like collapsible notch (656) to assist the old aged patients to break interface. [27] Fig 1 d depicts cut section of unit package where the solid (1 1 1 ) enclosed in backing membrane (334); and liquid (237) enclosed by supporting membrane (445); are separated by interface membrane (223) equipped with T-shaped spindle (200) which is required to be rotated and removed to break the interface and creating the opening to deliver the product by squeezing.

[28] Fig 1 e shows the side view of flexible unit package where the solid (819) is packed in backing membrane (821 ) closed by fragile, water impermeable interface (223). The liquid for reconstitution (237) and clump breaker (1 1 ) are filled in supporting membrane (445) equipped with inbuilt opener (200) at bottom which is required to be flipped to open package.

[29] Fig 1 f shows the side view of smooth single unit package where the solid

(1 1 1 ) and liquid (237) are separated by interface membrane (224). The solid is enclosed in backing membrane (335) and the liquid held by supporting

membrane (446). The notch (301 ) in path tube (617) is pressed to rupture the interface. The clump breaker (1 1 ) further assists in breaking of interface and even mixing. The package is opened by tearing the opener (201 ). The path tube is inserted into body cavities like oral, buccal, nasal, urethral, vaginal cavity or desired site to deliver the reconstituted product at site of action.

Fig.2

[30] Fig. 2a exposes the top view of single unit package with the solid (1 1 1 ) along with clump breaker (1 1 ), the path tube (422) and opener (321 ). The liquid side is hidden at bottom side.

[31 ] Fig. 2b exposes the top view of single unit package where the solid (1 1 1 ) after reconstitution by rotating the T spindle (200), allows the contents to squeeze out through path (422), after removal of spindle cum opener and pressing the package.

Fig.3

[32] Figure 3 shows some shapes of clump breakers (3a, 3b, 3c) along with

guided vanes (3d, 3e, 3f) to assist the breaking of clumps and interface, and delivery of reconstituted product. Fig.4

[33] Shows the steps involved in manufacture and usage of single pack. The figure 4a shows the filling of liquid (237) for reconstitution and sealing with interface. The figure 4b shows filling of solid (1 1 1 ) and clump breaker (1 1 ). Figure 4c is showing the joining both the sections with off-centering in proper alignment. For usage, the package is held as per figure 4d, pressed to break the interface (222) and allowing the liquid to drop down by gravity as shown in figure 4e. The package is initially bent at right angle as shown in figure 4f and pressed to squeeze the gel content (30) as shown in figure 1 g after mutilating the opening end (105).

Fig.5

[34] Shows steps involved in manufacture of modified single package with path tube extended from solid side. The figure 5a shows the filling of liquid (237) for reconstitution in support membrane (445) and figure 5b depicts the sealing with interface. The figure 5c shows filling of solid (1 1 1 ) and clump breaker with guided vane (1 1 ). Figure 5d is showing the closing of solid side with interface side of liquid section with alignment in such a way that the exposed interface (223) has minimum area to assist breaking up on pressing.

Fig.6

[35] Shows the top view of bunch or group of single unit packages (1 1 16) which required to be separated individually during usage. The solid (1 1 1 ) along with clump breaker (1 1 ) path (422) and the opener (321 ) are shown and the liquid is hidden at bottom side.

Description of Embodiments

[36] As an embodiment, the packing is equipped with two interfaces, one of which is combined with backing membrane to hold liquid and the other is closed with support membrane to hold the solid. Subsequently the interfaces are merged to off centered manner to get single packing with minimum interface area which assists breaking of interfaces. [37] As an embodiment, the packing is equipped with path tube (250) which extended from solid side as shown in figure 5. The interface membrane (223) and support membrane (445) enclose the liquid (237). The solid (1 1 1 ) is filled in backing membrane (334) then the guided van cum clump breaker (1 1 ) was kept in place which prevents the falling of solid when backing membrane is tilted and aligned off-centered manner to get sealed as shown in figure 5d. This

methodology keeps the minimal fragile interface area (223) exposed between two sides and readily broken when pressed to mix the solid and liquid.

[38] As another embodiment, the single packs (1 1 16) as the top views shown in fig 2a and 2b are joined as bundles to ease the handling or transportation.

Alternatively, the single packages are packed alone as individual packs or as group as shown in figure 6, with or without secondary and tertiary packages.

[39] As an embodiment, the another single package as shown in figure 1 d which is equipped with T spindle (200) in interface (223) membrane, backing membrane (445), support membrane (334). The T- shaped spindle cum opener is required to be rotated to break the interface and getting the solid reconstituted with liquid. The removal of T- spindle and squeezing of package causes extrusion of contents through the path at the site of usage.

[40] As another embodiment, single unit package as shown in figure 1 e, enclose the solid (819) in thick aluminum backing membrane (821 ) fragile puss through interface (223) which is made of thin aluminum, by cold forming. The liquid for reconstitution (237) and clump breaker (1 1 ) is filled in polypropylene supporting membrane (445) container equipped with opener (200) at bottom which is required to be flipped to open package for administration of reconstituted product.

[41 ] As another embodiment, single unit package as shown in figure 1 f, enclose the solid (1 1 1 ) and clump breaker (1 1 ) between backing membrane (335) and interface (224). The liquid for reconstitution (237) is filled in supporting membrane (445) equipped with opener (201 ) at end of path tube (617) containing notch (301 ) which is required to be pressed for breaking of interface.

[42] The interface used in this invention is made of material which is impermeable to the liquid used for reconstitution and having varied thickness to withstand the shocks during transport and handling, and get flexible enough to get ruptured during usage.

[43] The support membranes, backing membranes, interface membranes, notch, patch tubes, openers, clump breakers and T spindles mentioned above are mono-layered or multiply laminated, having the thickness in the range of 1 nanometer to 1 centimeter. The volume of the single packages on liquid side or solid side is ranging from 1 micro-liter to 1000 milliliters. The shapes of above packages are ranging from irregular or star shape or cuboids, or trapezoid or oval , biconvex to highly ordered spherical shape.

[44] As an embodiment, the package components are made of single or multiply laminates. The components are made of material such as metal like aluminum, or natural like rubber, or semi-synthetic origin, or synthetic like Poly chloro trifluoro ethylene (PCTFE), cyclic olefin copolymers (COC), cyclic olefin polymers (COP), poly vinyl chloride (PVC), poly vinylidene chloride (PVdC), polypropylene (PP), polyethylene (PE), paper, alone or in combination, with or without plasticizer, colors or adjuvant(s) to get desired barrier effect. The derivatives or combination of above mentioned materials are used with or without adjuvant(s) to improve the quality, performance, appeal, ease of usage, flexibility, toughness, inertness or other desired property. As an embodiment, all the components of package mentioned above are made of same material or each individual component is made from unique individual material or in combination to get desired effect.

[45] As an embodiment, the above mentioned packages can be labeled, printed or colored or engraved or embossed for the improved identification or branding or visual acceptability or convenience.

[46] As an embodiment, the above mentioned single packages can be used to

pack pharmaceuticals, foods, cosmetics, diagnostic or testing devices, or accessories or any products of other sector which require the separation of liquid and solid during storage and reconstitution of solid with liquid before usage.

[47] The single package of present invention is used to pack the solids which are having the shape ranging from highly irregular to sphere in form of powder, granule, bead, pellet, patch, film, tablet, capsule or any form which is required to be reconstituted before use. The liquid used for reconstitution is containing solvent, solution or dispersion of materials in water or non aqueous solvents.

[48] As an embodiment, the packing equipment used for the present invention

having platen or rotary sealing and uses cold forming, thermal forming, blowing, compression, stretching, molding or combination thereof.

[49] The invention will now be described with respect to the following examples which does not limit the invention in any way and only exemplify the invention.

Examples

[50] Example 1 : Preparation and evaluation of model dry solid for reconstitution with liquid to prepare topical gel of itraconazole to check the performance of single package as shown in figure 1 a. The composition of solid powder was shown in table 1 .

[51 ] Table 1 : Composition of dry solids for itraconazole gel

Ingredients quantity, gm

Itraconazole 2.5

Hydroxyl propyl methyl cellulose, 5 cps 20

Polyethylene glycol 4000 15

Glucose 2.5

Urea 2.5

Carbopol, 934 7.5

[52] Initially itraconazole mixed with urea and subsequently mixed with glucose, polyethylene glycol (PEG) 6000, carbopol and hydroxyl propyl methyl cellulose (HPMC) to get dry solid powder.

[53] Accurately weighed 2.5 gm of sodium acetate was dissolved to 50 ml with distilled water to get the liquid for reconstitution.

[54] 0.4 milliliters quantities of liquid for reconstitution was filled in blister slots

supporting membrane made of poly chloro trifluoro ethylene of thickness 150 micrometer. The blister was closed with interface membrane made of 20 micrometer thickness poly chloro trifluoro ethylene (coated on aluminum layer) by using thermal forming method. [55] Accurately weighed 100 mg quantities of dry solid powder was placed in blister slots of supporting membrane made of aluminum coated with poly chloro trifluoro ethylene with thickness of 200 micrometer. The solid powder was exposed to atmosphere of 90% relative humidity for 8 h and subsequently dried in dry atmosphere for 4 h as per the methodology mentioned in patent application PCT/IB2015/058829 to get solid compact structure. Clump breaker was placed on solid and closed with interface membrane (aluminum) side by using thermal forming method.

[56] The prepared package was evaluated for leaking, ease reconstitution, ease of extrusion of contents. The extruded gel was evaluated for pH, drug content, spreadability and anti-fungal activity.

[57] The drug content of gel was determined by agitating 0.1 gm of gel in 0.1 N HCI and then volume made up to 100 ml. The filtered solution was analyzed for itraconazole using UV visible spectrophotometer at 255 nm.

[58] For spreadability test, two borosilicate glass plates of size 20x20 cm ² were taken. 0.5 gm of gel was transferred on to one plate and second plate was placed on gel. Then 5 gm weight was added above the second glass plate. After 2 min, the minimum diameter of the spread gel was measured.

[59] The pH of gel was checked by placing pH paper on the gel surface.

[60] The microbial testing of antifungal activity of 100 mg of gel was performed using cup plate method using Sabouraud dextrose agar inoculated with Candida albicans as test organism.

[61 ] The prepared single pack of itraconazole powder blend along with liquid for reconstitution by thermal forming method produced intact pack without leakage. The single pack was taken in right hand and pressed with right thumb to break the interface to wet the solid to form gel. The opener was removed and the package was squeezed to get the gel for testing purpose.

[62] The extruded gel was translucent white in color. The drug content studies showed 0.998±0.013 mg of itraconazole per 100 mg of gel. The diameter of gel spread was found to be 3.1 ± 0.2 cm. The pH of gel was found to be neutral. The diameter of the zone of antifungal inhibition of by gel formulation is 4.8± 0.5 cm in comparison with 0.1 ml of 1 % suspension of itraconazole in purified water which showed zone of inhibition of 1 .6± 0.3 cm.

[63] Example-2: Preparation and evaluation of model dry solid for reconstitution with liquid to prepare topical gel of levofloxacin to check the performance of single package as shown in fig 5. The composition of solid powder was shown in table 2.

[64] Table 2: Composition of dry solids and liquid for reconstitution to prepare

levofloxacin gel

Ingredients Amount, gm

Levofloxacin 0.5

Hydroxyl propyl methyl cellulose, K15M 4

Polyethylene glycol 6000 4

Sodium citrate 4

Glucose 12

Sodium bicarbonate 0.49

SLS 0.01

Cetrimide solution, 0.1 % w/v in water 75

(Liquid for reconstitution)

[65] Initially levofloxacin was mixed with SLS, sodium bicarbonate and poly

ethylene glycol (PEG 6000), subsequently mixed with sodium citrate, hydroxyl propyl methyl cellulose, (HPMC) and glucose to get dry solid powder.

[66] Accurate weighed 0.1 gm of cetrimide was dissolved 100 ml of distilled water to get the liquid for reconstitution.

[67] 0.9 milliliters quantities of liquid for reconstitution was filled in blister slots supporting membrane made of aluminum. The blister was closed with interface membrane made of 15 micrometer thickness aluminum foil by using cold forming method as per steps mentioned in figure-5.

[68] Accurately weighed 300 mg quantity of dry solid powder was placed in blister slots of backing membrane made of polyvinyl chloride. The powder was exposed to atmosphere of 90% relative humidity for 8 h and subsequently dried in dry atmosphere for 4 h as per the methodology mentioned in patent application PCT/IB2015/058829. The clump breaker as shown in figure 3d made of poly chloro trifluoro ethylene was placed on the solid. Finally the solid and clump breaker was closed with aluminum interface side of liquid filled aluminum supporting membrane by thermal forming method.

[69] The prepared package was evaluated for leaking, ease of reconstitution, ease of extrusion of contents, pH of extruded gel, drug content, spreadability, viscosity and anti-bacterial activity of reconstituted gel.

[70] The drug content of gel was determined by agitating 0.2 gm of gel in 5 ml of 0.1 N sodium hydroxide solution and then volume made up to 100 ml with phosphate buffer pH 6.8. The filtered solution was analyzed for levofloxacin using UV visible spectrophotometer at wave length maxima of 294 nm.

[71 ] For spreadability test, two borosilicate glass plates of size 20x20 cm ² were taken. 0.5 gm of gel was transferred on to one plate and second plate was placed on gel. Then 5 gm weight was added above the second glass plate. After 2 min, the minimum diameter of the spread gel was measured.

[72] The pH of gel was checked by placing pH paper on the gel surface.

[73] The microbial testing of antibacterial activity of 100 mg of gel was performed using cup plate method using nutrient agar medium inoculated with bacillus subtilis as test organism.

[74] The prepared single pack was intact without leakage. The single pack was taken in right hand and pressed with right thumb on liquid side to break the interface. The liquid was allowed to fall by gravity for converting the solid to gel state. The package was bent at right angle and subsequently pressed to full extent as shown in fig 4. The package was alternatively pressed and released for one min to assist admixture. The opening end was mutilated and the package was squeezed to get the gel for usage.

[75] The extruded gel was translucent white in color. The diameter of gel spread was found to be 4.2± 0.3 cm. The pH of gel was found to be 6. The diameter of the zone of antibacterial inhibition of gel formulation is 4.6± 0.3 cm in comparison with 0.1 ml of 1 % suspension of levofloxacin in purified water which showed zone of inhibition of 1 .9± 0.1 cm. The reconstituted gel was having drug content of 0.50±0.03 mg per 100 mg of gel.

[76] The viscosity of reconstituted gel was estimated by using Brooke-field viscometer and found to be in range of 14000-18000 cps.

[77] The readymade reconstituted product was stored and observed for 3 months at room temperature. The readymade product got converted to brown color after 2 months, whereas the solid and liquid separately packed did not show any change in color.

[78] The reconstituted gel is suggested to be used for treatment within one month from date of reconstitution.

[79] Example 3: Preparation and evaluation of model dry solid for reconstitution with liquid to prepare suspension of lornoxicam to check the performance of single package as shown in fig. 1 e. The composition of solid powder was shown in table 3.

[80] Table 3: Composition of dry solids and liquid for reconstitution to prepare

lornoxicam suspension, gm

Ingredients Amount, gm

Lornoxicam 0.4

Hydroxyl propyl methyl cellulose, 5cps 2

Poly ethylene glycol 4000 (PEG 4000) 2

Sodium citrate 8

Glucose 12

Sodium bicarbonate 0.5

SLS 0.1

Cetrimide solution, 0.1 % w/v in water 75

(Liquid for reconstitution)

[81 ] Initially lornoxicam was mixed with SLS, sodium bicarbonate and PEG 4000, subsequently mixed with sodium citrate, hydroxyl propyl methyl cellulose,

(HPMC) and glucose to get dry solid powder. [82] Accurate weighed 0.1 gm of cetrimide was dissolved in 100 ml of distilled water to get the liquid for reconstitution.

[83] 0.9 milliliter quantity of liquid for reconstitution was filled in poly propylene

support container containing in built opener at bottom. The clump breaker as shown in figure 3d made of poly chloro trifluoro ethylene was placed. The container was closed by interface made of aluminum by thermal forming method.

[84] Accurately weighed 300 mg quantity of dry solid powder was placed in blister slots of backing membrane made of aluminum with 80 micron thickness coated with poly choloro trifluoro ethylene thickness of 5 micron on solid side,. The powder was exposed to atmosphere of 90% relative humidity for 8 h and subsequently dried in dry atmosphere for 4 h as per the methodology mentioned in patent application PCT/IB2015/058829 to get converted to solid sponge which will not fall by simple tilting. The solid was closed by interface side of liquid section by thermal forming method.

[85] The prepared package was evaluated for leaking, ease of reconstitution, ease of extrusion of contents, pH of suspension and drug content,

[86] The drug content was determined by agitating 0.5 gm of product in 5 ml of 0.1 N NaOH solution and then volume made up to 100 ml with phosphate buffer pH 6.8. The solution, 0.5 ml was diluted to 10 ml with phosphate buffer pH 6.8. The filtered solution was analyzed for lornoxicam using UV visible spectrophotometer at wave length maxima of 377 nm.

[87] The pH of suspension was checked by placing pH paper in product.

[88] The prepared single pack of lornoxicam dry powder blend along with liquid for reconstitution produced intact pack without leakage. The single pack was taken in right hand and pressed at top by right thumb on solid side to break the interface and the solid is allowed fell down by gravity and the aluminum foil got collapsed. The liquid side was alternatively pressed and released between index finger and thumb for 1 min to assist admixture. The opener end was detached after tilting the package and squeezed to get the suspension for usage. [89] The reconstituted product showed pH in the range of 6 to 7 and 4.0±0.12 mg of drug per 1 ml of dispersion. The reconstituted suspension is suggested to be used as pain killer.

[90] While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the invention. These and other changes in the preferred embodiment of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.

Industrial Applicability

[91 ] The main application of present invention is to provide single packaging

system for solids along with liquid which is used for reconstitution before usage.

[92] Still further application of the present invention is to separate both solids and liquids in single pack which improve stability and enhance expiration period.

[93] Another application of present invention is to provide deliverable unit doses, or measured quantities which prevent the necessity of providing measuring device along with package.

[94] The other application of present invention is to provide package system which is user and environmental friendly and hence acceptability to market is improved with better compliance for wide sectors to name a few: pharmaceuticals, foods, cosmetics, diagnostics, reagents and allied fields.

Citation List

[95] Patent application PCT/IB2015/058829 was cited to prepare powder

combinations for reconstitution and subsequent package.

Patent Literature

[96] PTL1 : US 20150297458: Rapid reconstitution package includes a

substantially cylindrical structure including a diluent chamber and a drug chamber communicating through a valve. [97] US 20140350482: Reconstitution device used plungers /screws to assist mixing.

[98] United States Patent 8562582 reported a reconstitution device contains cap having a first end secured to the receptacle, a second end, and an inner bore having a central aperture.

[99] United States Patent 9044536 showed reconstituting infusion device equipped with hidden patient needles.

[100] PCT/US2007/069639 reported a recipient closed by a stopper.

[101 ] US 6358236 reported a device for reconstituting medicaments for injection which contains a housing having an upper section capable of receiving a syringe and a lower section capable of receiving a vial containing the medicament.

[102] US 20130319885 showed compact medication reconstitution device and

method in which the barrel component has a spiral mixing channel near its distal end in which powder medication is stored.

[103] The blister packing device was disclosed in WO/2016/037626A1 for

pharmaceutical compositions or supplements.

[104] Re-closable blister package assembly was reported in United States Patent 7958998 which provides a re-closable blister package assembly for

accommodating center-filled gum pieces.

[105] A system for opening a medical blister package was reported in

WO/201 1 /1 13440A1 comprising a carrier sheet with at least two separate depressions adapted to accommodate pharmaceutical compositions.

[106] WO2007/097452 reported a medical package which has the direct

communication between the solid preparation and drying agent to reduce foul odor.

Non Patent Literature

[107] NPL1 : The marketed product of Kinder joy has two receptacles to separate the actual product and free gifts, joined as single pack. But the single is divided to two individual packs and peeled each pack separately to receive each

component of two packs separately without reconstitution.