INTRODUCTION:

The administration of drug through oral cavity is more convenient, cost-effective, and entails foremost of patient compliance. However, oral route sometimes may be complicated for the reason of the swallowing difficulty particularly for pediatric and geriatric patients who have fear for choking of drug. Patient convenience and compliance-oriented research have resulted in bringing out safer and newer drug delivery systems. For such patients, various novel approaches including the oral fast-dissolving drug delivery system emerged as a blessing. These formulations could be administered devoid of using water or a requirement of chewing. Historically, orodispersible films were first introduced as mouth fresheners in the trade as dental strips¹. Orodispersible films or oral disintegrating strips are defined as a solid formulation that having disintegration time of 30 seconds or less as per the guideline of the US FDA.

The oral disintegrating drug delivery system mainly comprises of two types, namely, oral disintegrating tablets and orally disintegrating strips/films². Oral disintegrating films are mainly thin oral strips that get absorbed readily after they are placed inside the buccal cavity. These ultrathin films are typically 50-150 microns thick and organized by means of hydrophilic polymers. The use of hydrophilic polymers results in the quick disintegration of the strips on contact with saliva^3-4. Oral disintegrating films have gained wide acceptance and presently this delivery system is globally used for active pharmaceutical ingredients⁵.

Switching towards the classification of oral drug delivery system, are categorized in three main classes that are as follows.

· Sublingual delivery, in this method of delivery the drug is usually liberated via the mucosal membranes lining present at the base of the mouth.

· Buccal delivery is the delivery system for the drugs, through the mucosal membranes lining the cheeks.

· Local delivery, the way across which the drug is administered via the oral route.

The sublingual delivery system is permeable and gives quick absorption⁶. If we compare both the delivery system we found that the buccal mucosa is considerably less permeable apart from the sublingual area and that is not capable to anticipate the prompt absorption as well as good bioavailability seen with sublingual administration. Even though the sublingual mucosa is relatively more permeable as compared to the buccal mucosa, somewhere it is not suitable for oral transmucosal delivery system. The sublingual route is unsuitable as it makes device placement complicated due to continuous washing generally by saliva. However, device placement is easy in buccal mucosa for oral transmucosal delivery⁷. According to a formulation point of view, the thin mucin film that exhibits biological activity onto the surface of the oral cavity provides the pharmaceutical scientist with an opportunity to retain delivery systems in contact with the mucosa for prolonged periods with the help of mucoadhesive compounds⁸. Considering the mucoadhesion, which is an interfacial phenomenon which consist of two materials, and one of them is the mucus layer of the mucosal tissue are held together by channels of interfacial forces for extended periods. Such a phenomenon fascinates the salient features of controlled release system by localizing the drug into the particular region and thus improving and it also enhance the bioavailability of the drug. In addition to this the strong and solid interaction between the dissimilar polymers and mucus lining of tissue increases the contact time and permits the localization, which is an important factor in protein-peptide drug delivery⁹. In fact small molecules (< 75-100 Da) appear to cross the oral mucosa rapidly. Drugs with a specific site of absorption in the gastrointestinal tract, daily dose of the order of a few micrograms and with a half-life ranging from 2-8 hrs are good applicant for bioadhesive products¹⁰. More specifically orodispersible is a thin film which is simply functional in the buccal area to diffuse throughout the oral mucosa and enter straight into the bloodstream of the body. Furthermore the Oral drug delivery system may dispense better and greater bioavailability along with rapid onset of action when compared to other oral administration. To be more precise oral films are non-sticky, non-tacky, non-curving instantly wet and quickly dissolve dosage form¹¹.

Advantages and Limitations of OTF:

Orodispersible thin films (OTF) have several advantages over regular medications including fast dissolution time and ease of application. The inimitable properties such as higher mechanical strengths and low-cost lyophilization processes have made OTF a highly valuable invention in the pharmaceutical industry¹². In contrast, the expensive packaging method and restriction in high dose loading are certain disadvantages of oral strips¹³. The principal advantages and limitations of OTF are discussed in Table 1.

Table 1: Advantages and limitations of Orodispersible thin films

Limitations	Advantages
In some cases, eating and drinking is restricted after the film consumption	No risk of choking after the ingestion, suitable for patients who have a problem in swallowing, especially in pediatric and geriatric patients
Larger doses cannot be administered	Convenient and accurate dosing
For drugs not stable at buccal pH cannot be administered through this route	Enhanced stability, rapid onset of action, ease of transportation compared with solid doses
Packaging is difficult	Fewer chances of side effects due to low dose films

Classification of OTF:

OTF are well known as a fine, pliable, non-friable polymeric strip, having one or more than one dispersed active pharmaceutical ingredient, which is intended to be positioned into the oral cavity. OTF can be categorized in various categories based upon the physico-chemical nature, pharmacological action and mode of application. Figure 1 illustrates the various types of films on the foundation of onset of action they produced.

Orally Dispersible Strips (ODS):

These are made-up of hydrophilic polymer that resists the property to disintegrate the drug in short duration of time and low quantity of water is needed. Even it is the most advance form of the solid dosage form. It is generally available as single layer strips having active pharmaceutical ingredients on it.

Fused Away Strip:

Melt away strip are differentiate from other ODS due to drug which have low melting point that they can liberate the API after wetting on tongue.

Non-disintegrating Strip:

These strips have tendency to produce biological effect on substantial concentration of the saliva in the oral mucosa.

Fused Away Strip with Taste Masking Agent:

These are modified release strip specialized in some major physical property like taste masking, in addition to that some polymers which formularized with various film formers and plasticizers so that to intend the bitterness of a drug and making the pharmaceutical dosage form more convenient and patient compliant^14-16.

Table 3: Polymer used in Formulation of Different Category of Drugs^28-86

Sr. No	Category	Drug	Polymers	Method
1.	Anti-hypertensive	Lercanidipine Hcl	PEG 400 TPGS 1000	Evaporated antisolvent evaporated method
2.		Propranolol	PVP PVA Gelatin Chitosan	Solvent Evaporation Method
3.		Carvedilol	Methylcellulose, Hydroxy Propyl Methyl Cellulose, Eudragit	Solvent Casting method
4.		Metoprolol Succinate	HPMC, Chitosan, PEG
5.		Nebivolol	HPMC HEC MC
6.		Diltiazem HCL	HPMC K4M Eudragit
7.		Lisinopril	HPMC K4M, Sodium CMC, Eudragit RL 100, Carbopol 934
8.		Nifedipine	HPMC E-5, PVP, PEG-400
9.		Captopril	Hydroxy Prophyl methyl cellulose, Pullulan
10.		Enalapril Maleate	Hydroxy prophyl cellulose, Polyethlene glycol
11.	Anti-Emetic	Granisetron hydrochloride	HPMC, PVP K-30	Solvent Casting method
12.		Ondansetron hydrochloride	Hydroxy Prophyl methyl cellulose
13.		Palonosetron	Eudragit, proloc 15
14.		Prochlorperazine	HPMC Ethyl cellulose	Solvent Casting method
15.	Anti-inflammatory (NSAID)	Indomethacin	Ethanol Acetonitrile HPMC Tween 80	Solvent Casting method
16.		Meloxicam	HPβCD PVP
17.		Prednisolone	HPMC, Carbopol, Eudragit
18.		Ibuprofen	HPMC, PEG
19.		Flufenamic acid	Kollicoat, chitosan, glycerol
20.	Anti-Histamine	Levocetrizine HCL	Eudragit, HPMC E5, PVA,
21.		Promethazine HCL	HPMC E15, PEG400,
22.		Desloratadine	Maltodextrin, HPMC E-5
23.		Loratidine	HPMC, Eudragit
24.	Anti-Fungal	Miconazole nitrate	Chitosan, hydroxyl propyl methyl cellulose
25.		Clotrimazole	Sodium carboxymethyl cellulose, carbapol
26.		Nystatin	Polyethylene oxide, Carmellose sodium
27.		Griseofulvin	Pullulan, Xanthan gum
28.	Anti-Migraine	Rizatriptan benzoate	hydroxypropyl methylcellulose (HPMC K4M), polyvinyl alcohol (PVA), polyethylene oxide (PEO), glycerol	Solvent Casting method
29.	Anti-Migraine	Zolmitriptan	Sodium Alginate, Xanthan gum, Sodium starch glycolate, guar gum	Solvent Casting method
30.	Anti-Depressants	Diazepam	HPMC E3, E5, and E15, Propylene glycol, PEG 400	Solvent Casting method
31.		Tianeptine Sodium	Hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and polyvinyl alcohol), maltodextrin, polyvinyl pyrrolidone K90 and lycoat RS780
32.		Sertraline	HPMC, PEG,PVP
33.		Duloxetine hydrochloride	HPMC, PVA
34.		Doxepin HCL	Chitosan, Sodium hydroxypropylmethylcellulose(HPMC) sodiumcarboxymethylcellulose (SCMC)	Solvent Evaporation method
35.	Hypnotic-sedative	Midazolam Hcl	HPMC, Pullulan	Solvent Casting Method
36.	Opium alkaloid antispasmodic drug	Papaverine Hcl	HPC, PVA	Solvent Casting Method
37.	Antiseptic	Chlorhexidine	HPMC, Chitosan, sodium alginate	Solvent
38.	Antispasmodic drugs	Tizanidine HCL and Meloxicam	HPMC E-15, Arabinoxylan
39.	Antibiotic, Antiinflammatory	Ornidazole and Dexamethasone	HPMC, Chitosan, Polyvinylalcohol, EC
40.	Anti-diabetic	Glibenclamide	HPMC with different ratio	Solvent Casting method
41.	Anti-convulsant	Clobazam	PEG600, SSG
42.	Antianginal, antiarrhythmic antihypertensive	Verapamil	HPMC E-6, Maltodextrin
43.	Antiparkinsons	Ropinirole	HPMC 603, PEG 400,
44.	Antioxidant, anti-inflammatory, antiviral, antimicrobial, and anticancer	Curcumin	Chitosan
45.	Antidiabetic	Metformin hydrochloride	Chitosan, Starch, Sodium Starch Glycolate, Microcrystalline cellulose
46.	Antiarrhythmic	Lidocaine HCL	Hydroxy propyl cellulose, PEG, Kollicoat, Hydroxypropyl pea starch polymer, lycoat.
47.	Sedative/ Hypnotic	Zaleplon	Lycoat NG 73, kollicoat, HPMC E15, propylene glycol.
48.	Corticosteroids	Fluticasone Propionate	sodium carboxymethyl cellulose (SCMC), Carbopol 971P
49.	Anti-diuretics	Spironolactone	Poly ethylene glycol 400, Poly vinyl alcohol
50.	Stimulant	Caffeine anhydrous	PVA, PEG, Pullulan, Maltotriose
51.	Anti-ulcer	Omeprazole	Metolose, Ethanolic gels, polyethylene glycol 400, L- Arginine
52.	Anti-Miagraine	Rizatriptan benzoate	HMPC PVA
53.	Anti-tuberculosis	Isoniazid	Kollicoat® IR
54.	Coticosteroid	anhydrous theophylline	HPMC( Pharmacoat® 606), ammonio methacrylate copolymer type B (Eudragit® RS), Ethylcellulose
55.	Cholinesterase inhibitor	Donepezil	HPMC, PVA
56.	Analgesic	Ibuprofen	HPC
57.		Acetaminophen	Hydroxy Prophyl methyl cellulose, Polyethlene glycol, Poly vinyl alcohol	Emulsion Solvent Evaporation method
58.	Fluoroquinolones	Enrofloxacin	PolyvinylPyrrolidone	Solvent evaporation method
59.	Broncodialtor	Salbutamol	HPMC	Hot melt extrusion method

TECHNIQUES FOR PREPARING OTF:

Solvent casting method:

As this technique is most preferable method for the preparation of OTF. In this method the two solutions are assembled separately. In first solution, hydrophilic polymers are solubilized in the water at 1000rpm and the temperature is maintained up to 60˚C so that a clear viscous solution is obtained. While in second solution, the other excipients like sweeting agent, flavoring agent as well as coloring agent are dissolved in it. Now both the solutions are assembled together further proceed for stirring. Then, the API is dissoluble in suitable solvent and the formerly prepared mixture is incorporated into it. Finally, the proceeded solution is cast as a strip and allowed it to dry and before packaging, the strips are cut into desired size⁸⁷ and showed in Figure 2.

Figure 2: Flow Chart of Solvent casting method

Hot melt extrusion:

An another method for devising of OTF is hot melt extrusion method in which a polymer is converted into a film via the heating process. Firstly, a mixture containng all excipients along with API is pour into the hopper and then it is conveyed for obtaining a fine mixture which is further processed for the heating process in extruder. After that, the material comes out into the molten state. Finally, this melted material is used for the formulation of strip. However, casting and drying process is very critical step during this process⁸⁸. Over all, due to certain pros of this technique the method is broadly adopted for the formulation of strips. The diagram of this method showed in Figure 3.

Figure 3: Hot Melt Extrusion method

Semi-solid Casting:

Semisolid casting technique is executed by the accumulation of water-soluble polymer which are dissolvable in water. After that, the prepared solution is incorporated into the acid –insoluble polymer in a ratio of 4:1. After mixing both the solutions, the active ingredient (Drug) together with plasticizer are added in approptriate amount simultaneously. At last, gel mass is casted into strips by heating, utilizing heat controlled drums⁸⁹.

Solid Dispersion:

In the Solid dispersion method active pharmaceutical ingredient (API) is dispersed into a solution with suitable solvent, depending upon the chemical and physical properties of the API. When a proper solution is established, then the solution is inserted into the melted polymer along with some unmixed ingredient, where the temperature is kept of below 70°C. Ultimately, the collected solid dispersion is twisted into strips by using assorted dyes⁹⁰.

Rolling:

In the rolling method, the drug solution and polymer solution are assorted together so as to achieve form a suspension. Further the mixture is rolled on carrier. The solvent is water and alcohol mainly. The solution is dried to the roller and in the end, it is cut to obtained a strip of desired size and shapes⁹¹.

Printing:

Printing can be pooled with distinct oral strip manufacturing technologies to empower higher level of sophistication. High potent drugs along with fixed dose combinations can be formulated with the aid of the shelf consumer inkjet printer or flexographic printer. Additionally, three dimensional printing technique can be tailored or on-demand fabrication or custom made medication. 3D printing for oral film formulation depends on the choice of technology, where single or multiple dosage formulation can be couched. In this technique, a basic drug free film is constructed by solvent casting method, and after that the drug is incorporated into base film by printing. This technique optimizes complexity and sophisticated bioactive construct⁹².

EVALUATION PARAMETERS:

These parameters assist as the detectors for the compliance of OTF formulation and are performed to actually evaluate the eminence of a product. Aside from this, these parameters are mention as the standard test for determining the quality and reliability of an OTF under certain monographs before promoting to the retailer. In order to this, these specific tests outcomes are reported and compare with the standard parameters and then referred to the patients through prescription by the physician. Anyhow, the names of test along with comprehensive procedure are mentioned below^93-104:

Thickness test: This test is performed to examine the thickness of the strips using vernier calliper or micrometer and for this purpose three samples of each formulation are taken.

Weight of the strip: All films were weighed onto a digital weighing balance, and their influences were noted. Calculate the average weight of the strip.

Folding endurance: The Folding endurance test of oral disintegrating strips is determined by folding each strip at the interchangeable place repeatedly till its break down. Count the digits of the folded strip while it breaks.

Surface pH: The surface pH of the strip is calculated by selecting the three strips of each formulation. The strip is placed on the surface of the agar plate for 2hours. After 2 hours the strip swells and the pH is calculated by using the pH paper functionally on the surface of the swollen Strip. A mean average is to be recorded.

Percentage elongation: The elongation percentage is intended by utilizing custom elongation testing apparatus; the percentage elongation is determined by using equation 1

Percent elongation= [L2-L1]/L1x100

Where, L1 is the initial length and L2 is the final length of the strip

Percentage moisture content: The prepared strips are weighed individually and discretely further it kept in a desiccator containing fused calcium chloride at room temperature for 24 h. After 24 h, the strips are weighed and the percentage moisture content is determined from the below mentioned formula-

(Initial weight − Final weight)

Percentage moisture = ----------------------------------×100

Content Final weight

Moisture uptake, swelling ratio and erosion studies: Strip specimens (1cmx1cm) are taken for moisture uptake, swelling ratio and erosion studies. For moisture uptake study, the strip specimens are initially weighed (W₀) and then placed in stability chamber set at 25±2°C temperature and 75% relative humidity. The specimens are removed after constant weight is achieved (W_u). Moisture uptake is calculated by the following equation:

W_u-W₀

Moisture uptake = ---------------

W₀

For swelling ration and erosion studies strips are dried overnight at 60±2°C. Then the strips are weighed (W₀) and dipped in 5ml of distilled water. After that the strips are placed in stability chamber set at 25±2°C temperature and 75% relative humidity for 48hours. These hydrated strips are weighed (W_s) and then dried again at 60±2°C overnight, and weighed again (W_d). The percentage swelling ratio and percentage erosion are then calculated by following formulas given below;

W_s – W₀

% Swelling ratio = ----------------- X 100

W₀

W₀ – W_d

% Erosion = ----------------------- X 100

W₀

Percent drug content:

Strips of 2cmX2cm are cut from different locations. Each strip sample is soaked in phosphate buffer (pH 5.5) in 10ml volumetric flask and then sonicated at 25°C for 30min. The solutions are further centrifuged for 15min at 5200rpm. Finally the solutions are filtered through 0.45mm filters and analyzed spectrophotometrically.

In-vitro Dissolution studies: USP dissolution apparatus is used for the study. The temperature of the apparatus is kept at 37± 0.5˚C. The speed of the rotation is 50rpm. An Aliquot of a sample is withdrawn at a specific time interval and the capacity of the sample is replaced by the fresh medium. The sample is analyzed spectrophotometrically at specified wavelength and further comparing with standard mention in the pharmacopeias.

In-vitro Disintegration test: Disintegration time is the time when an oral film starts breaking when brought in contact with water or saliva. For an oral disintegrating strip, the time of disintegration should be in the range of 5-30 s.

Stability Studies: The prepared strip is wrapped in a butter paper which further wrapped in an aluminum foil. The wrapped strip should be placed in an aluminum pouch and make it heat sealed. The formulations are kept at 30˚C/60% relative humidity (RH) and 40˚C/75% I stability chamber. After 3 months the formulations are evaluated for physical appearance, disintegration time and drug content, mainly to find out the stability of the final product.

Transparency: This test is performed by using UV spectrophotometer. Transparency is calculated as follows:

Transparency = (log T600)/b = −€c

Where T600 is the transmittance at 600nm and b is the film

thickness (mm) and c is concentration

Permeability studies: The Franz diffusion cell consists of a donor and a receptor compartment. In between the two compartments, mucosa is mounted and the size of the mucosa should be of identical size as that of the head of receptor compartment. The receptor compartment is filled with buffer and maintained at 37 ± 0.2°C and to maintain thermodynamics a magnetic bead stirring at a speed of 50 rpm is utilizing in this process. A film specimen moistened with a few drops of simulated saliva should be kept in contact with mucosal surface. The donor compartment consist at least 1 ml of simulated saliva fluid of pH 6.8. At particular interval, samples are withdrawn and replaced by same amount of fresh medium. By suitable analytical method, percentage of drug permeated can be determined.

REGULATORY PERSPECTIVE:

The BP, USP and Ph. Eur. Pharmacopoeias allocate monographs of all conventional dosage form include orodispersible tablets, medicated chewing gums, oro-mucosal preparations and lyophilisates etc.. But the monographs and specifications of numerous dissolution and disintegration profiles for oral films are yet to be esteemed. Moreover, in the pharmaceutical technical procedures there is inaccuracy occurs for analysis, quality control and process of oral films¹⁰⁵. The guidelines yet not described for dissolution and disintegration, so the recommended conditions such as volumes of dissolution media do not contemplate the natural conditions in the oral cavity. Although the guidelines for industry have been recently provided by EMA and US FDA, especially in development of formulations for vulnerable patient groups including the pediatric and geriatric inhabitants, further research is indispensable to demonstrate global standards since many of the reported studies are vary greatly, mainly in the methodology, procedures and approaches too, and it became more laborious to tell which is appropriate for a particular system.

GAME CHANGER FOR THE MARKET:

Oral thin film is the best alternative for manufactures to extend the life cycle of their product or nearly patent expired drugs and therefore will continue to create the interest of patients, clinicians, and pharmaceutical industries. In the current scenario, oral films are also utilizing in nutraceutical and cosmeceutical industries with huge financial benefits. Some national and international companies of repute actively accelerate their research towards oral films like LTS Lohmann Therapie-Systeme AG (Germany), Aquestive Therapeutics (U.S.), Indivior PLC (U.S.), AdhexPharma, Zim Laboratories Ltd. (India), CURE Pharmaceuticals (U.S), and Shilpa Medicare (India). Moreover, some companies also patent their technology for the development of oral films like Thinoral® by Zim Lab., CUREfilm® by Cure pharmaceuticals, PharmFilm® by Aquestive Therapeutics. Howerver, Aquestive Therapeutics recently received approval from US-FDA for oral films like Libervant (Diazapam, 2020), Exservan (Riluzole, 2019), and Sympazan (Clobazam, 2018)¹⁰⁶.In future, oral strips will become the game-changer for the global market. For instance, a market survey (Market Research Future) indicates that the global market for oral thin strips manufacturinssg will climb significantly by 2023 with a worth of US$ 4068.7 and CAGR at 10.50%. Furthermore, another study predicts that the market growth of all novel drug delivery systems, including ODS, will grow at a more modest CAGR of 2.9% over the same time¹⁰⁷.

Apart from this, the regional analysis of CAGR in oral thin strip market in the variant regions i.e. America, Europe, Pacific Asia, The Middle East and Africa signifies that American market would achieve CAGR of 10.72% in coming years. Moving towards European market, which were supported by the Government for the availability of health care funds and this market was also assisted by the France, Germany and the UK to escalate their CAGR. At the same time, the other regions of the world mainly The Asia Pacific (India, China and Japan), Middle East and Africa have been projected their growth USD 543.3 by the end of 2023. However, the market analysis of the Middle East and Africa shows faint growth, which also owes less economic development in this particular region; that’s why a high healthcare budget is now expected to uplift the health care market for future economic development¹⁰⁸.

CONCLUSION:

The biopharmaceutical profile of oral strip is largely accepted among all the potential patients due to its wider patient compliance. It is emerging as promising drug delivery approach especially for geriatrics and pediatrics, psychiatric patients with dysphagia. In the present review polymers utilized, drugs incorporated, preparation methods, evaluation studies and regulatory perspective of oral thin films have been summarized. It is evident from the study that in future oral strips can be promising drug delivery system to treat varied ailments with rapid onset of action. This delivery system can prove to be most widely used drug delivery system due to its ease of preparation and administration for all age groups. Consequently, it extends the product life cycle and patents upon the drugs present in the market. Hence, OTF technology proves to be a boon for both the consumers and pharmaceutical industries.

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Received on 28.04.2021 Modified on 03.06.2021

Research J. Pharm. and Tech 2022; 15(1):447-457.

DOI: 10.52711/0974-360X.2022.00074

Sr. No	Name of Polymer	Synonym	Description	Applications	Properties
Sr. No	Name of Polymer	Synonym	Description	Applications	P^H	Solubility
1.	Pectin	Citrus pectin, methopectin, methyl pectin, methyl Pectinate.	Coarse or fine, yellowish-white, odorless powder with mucilaginous taste.	Adsorbent, bulk-forming, emulsifying, gelling, thickening and Stabilizing agent.	6.0-7.2	Insoluble in ethanol (95%), Soluble in water.
2.	Maltodextrin	Glucidex, Glucodry, Lycatab DSH, Maldex, Maltrin, Maltrin QD.	tasteless, odorless, white powder or Granules.	Diluents, binder, Coating and Viscosity - increasing agent.	4.0-7.0	slightly soluble in ethanol (95%), freely soluble in water.
3.	Guar gum	Galactosol, guar flour, jaguar gum, Meyprogat, Meyprodor, Meyprofin.	An odorless, white to Yellowish -white powder with a bland taste.	Binder, Disintegrant, suspending, thickening, stabilizing, and viscosity increasing agent.	5.0-7.0	Insoluble in organic solvents
4.	Xanthan gum	sugar gum, Keltrol, polysaccharide B-1459, Rhodigel, Vanzan NF, Xantural.	white-colored, odorless, Free -flowing, fine powder.	Stabilizing, suspending and viscosity-increasing agent	3-12.	Insoluble in ethanol and ether. soluble in cold or warm water.
5.	Starch	Amido, Amidon, Amilo, amylum,	Odorless and tasteless, fine, white-colored Powder.	Binder, diluent, and disintegrant.	5.5-6.5	Insoluble in cold ethanol (95%) and Starch swells instantaneously in water.
6.	Chitosan	β- 1, 4-poly-D-glucosamine, poly-D-glucosamine.	Odorless, white or creamy-white powder	Coating, disintegrant, film-forming, Mucoadhesive, Binder and viscosity-increasing agent.	4.0-6.0	Insoluble in ethanol (95%), other organic solvents, sparingly soluble in water.
7.	Pullulan	Pululan, Pullulan Standard 180	White strand or ground into powder is tasteless, odorless	Binder, Coating, and Flocculating agent.	6.8	Insoluble in methanol, acetone, ethanol, but dissolves readily in water.
8.	Lycoat NG	Lycoat NG Lycoat RS	Neutral taste and odor.	Film forming, Coating agent.	6.8	Insoluble in a pure solvent, soluble in hot and cold water.
9.	Sodium alginate	Algin, alginic acid, sodium salt, Kelcosol, Keltone, Protanal, sodium polymannuronate.	Odorless and tasteless, white to pale Yellowish - brown colored powder.	Binder, Stabilizing, suspending and viscosity-increasing agent.	7.2 for 1% w/v aqueous solution.	Insoluble in ethanol (95%), ether, chloroform, Slowly soluble in water.