Abstract
Context:
Oral administration of drugs remains the most common and preferred route for many active pharmaceutical ingredients (APIs). However, solid oral dosage forms may be limited for patients who have swallowing problems or fear of choking. Furthermore in the case of solid dosage forms, disintegration and dissolution of dosage forms are rate limiting steps mostly for hydrophobic drugs' absorption and bioavailability. Liquid oral dosage forms such as syrups, emulsions or suspensions may be used to overcome these disadvantages but higher costs of their production and larger volume and dimensions of their packaging along with the lower precision in dose intake make the liquid oral dosage form less acceptable for patients and pharmaceutical industries.Evidence Acquisition:
In order to merge the advantages of both solid and liquid oral dosage forms, fast dissolving drug delivery systems have been developed over the years. The current review aimed to discuss the pros and cons of different preparations of oral fast dissolving dosage forms including tablets, films and nanofibers.Results:
Fast dissolving dosage forms rapidly dissolve in mouth without the need for additional liquid or chewing, providing ease of use for consumers, a fast absorption of drug, quick onset of action, and improved bioavailability. Various technologies to fabricate these dosage forms such as lyophilization, spray drying, solvent casting, hot melt extrusion, compaction and electrospinning are also addressed.Conclusions:
Fast dissolving drug delivery systems are the promising approach in oral drug delivery systems, which can provide patient compliance especially in case of pediatrics and geriatrics. They can also lead to quick action of drugs and enhanced bioavailability.Keywords
1. Context
Oral route is the most preferred and acceptable route for patients and medical practitioners that is the reason pharmaceutical companies are encouraged to develop oral dosage forms for various patients (1, 2). Although, despite their convenience, development of dosage forms which can be used orally without the need for water and with fast acting properties is still in progress (3). Fast dissolving systems (FDS) are drug dosage forms which dissolve in the oral cavity without the need for drinking water or chewing (4). These systems were first developed in 1970 and became favorable very quickly (5, 6). At first these systems were in the form of tablets (7) but with the advancement of technology, different dosage forms such as films (8), wafers (9, 10), buccal (11, 12) and sublingual (13) patches (14) were formed. They can be used for local or systemic delivery of drugs.
2. Evidence Acquisition
The current review studies the major types of fast dissolving systems studied in research papers or commercially produced; including tablets, films and nanofibers. The advantages and disadvantages of these fast dissolving systems are addressed, and their preparation and evaluation techniques are discussed.
3. Results
3.1. General Advantages of Fast Dissolving Systems
As defined by their name, fast dissolving systems are used in conditions where there is a need for local or systemic fast delivery of drug, which makes them possible to be administered anytime and anywhere without water (4, 15-20). Due to these characteristics, fast dissolving dosage forms are suitable for geriatrics (21), pediatrics (21), people with swallowing problems, nauseated people, people who have fear of choking (22, 23) when swallowing a solid dosage form, bedridden patients and people who do not have access to water (24-26). Fast dissolving drug delivery systems have better patient compliance and may offer improved biopharmaceutical properties, improved efficacy and better safety compared to the conventional oral dosage forms (27). Rapid onset of action, improved stability, first pass effect by-pass and increased bioavailability lead to increase the demand in pharmaceutical market (28, 29). In addition to their fast dissolution in water (saliva) and absorption from the oral cavity, they can enter the systemic blood circulation without undergoing first pass effect (30, 31). Therefore, they may have higher bioavailability, a lower Tmax and a higher Cmax. (20, 32). Other advantages include availability in a variety of shapes and sizes, not leaving a residue in mouth, and having acceptable taste (33).
3.2. Disadvantages of Fast Dissolving Systems
Although the hygroscopicity is preferred for fast dissolving of the drugs, it is also the most important drawback of these systems (7), which need special requirements such as packaging. Furthermore, particular dosage forms may have their own disadvantages including choking for tablets and inefficiency for high drug loading in films and nanofibers (13, 32). Released drug from fast dissolving dosage form in the mouth has a strong contact with taste buds on the tongue, this could be challenging for drugs with bitter taste (17, 33-35), which needs taste masking techniques.
3.3. Formulation Ingredients
Depending on the type of fast dissolving system that is to be manufactured, different ingredients are used. They are more or less the same in different dosage forms and will be explained briefly (35-38). It should be noted that not all ingredients are common for all types of FDS (28, 29).
3.3.1. General Ingredients
3.3.1.1. Active Pharmaceutical Ingredient (API)
Several drugs of different pharmacological classes are used to prepare fast dissolving systems including analgesics such as acetaminophen and caffeine (28), indomethacin (39), ibuprofen (40) and diclofenac (41, 42), anti-migraines such as donepezil (43, 44) and sumatriptan (13, 45), anti-emetics such as metoclopramide and dimenhydrinate, antibiotics (46) and miscellaneous categories (15, 31, 33, 47, 48).
3.3.1.2. Saliva Stimulating Agents
Since FDS are supposed to be used without water, they need to be dissolved in saliva; hence, to increase the rate of dissolution, the saliva stimulating agents can be used in some formulations. However drugs such as ascorbic acid and nicotinamide can stimulate the excretion of saliva by itself (4, 49).
3.3.1.3. Flavoring Agents
Most drugs have bitter taste and because these dosage forms are absorbed through the oral cavity, contact with taste buds is very likely. Flavoring agents are added to mask the bitter taste of drugs (50).
3.3.1.4. Coloring Agent
Some drugs and excipients have different shades of color and a non-uniform appearance is not attractive for the patients. Therefore, coloring agents and opacifiers are used to maintain a uniform color and appearance (51, 52).
3.3.1.5. Surfactants
In FDS formulations with some insoluble or poorly soluble ingredients, an appropriate surfactant may be used to improve the dissolution rate of the drug (53-55).
3.3.2. Specific Ingredients
In addition to general ingredients that can be used for all FDS, each system could have its own specific ingredients that are mentioned in Table 1 and explained briefly.
Specific Ingredients of Different Fast Dissolving Systems Dosage Forms
3.3.2.1. Polymers
Are among the most important excipients used in FDS. Interaction between API and polymer determines the amount of loading and rate of dissolution. Hydrophilic natural or synthetic polymers can be used to prepare fast dissolving films or strips (61-65). Some of the common polymers used to manufacture films or nanofibers are poly (lactide-glycolide) (40, 66), chitosan (67, 68), collagen (69), poly (lactide-caprolactone) (70, 71), cellulose acetate phthalate, polyvinyl alcohol (53, 72, 73), polyethylene glycol, polyvinyl pyrrolidone (12, 27, 47, 74-77) and cellulose derivatives such as hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) (48).
3.3.2.2. Plasticizers
They are used to improve the film’s mechanical strength and prevent breaking due to fragility (63, 78, 79).
3.3.2.3. Super Disintegrants
These excipients including microcrystalline cellulose, hydroxypropyl methyl cellulose, modified starch, cross-povidone and crosscarmellose are used in a concentration of 5 - 10% to ensure rapid disintegration of tablets in order to enhance dissolution rate and quick absorption of drug. Super disintegrants do their function through different mechanisms; they can swell in contact with water or improve the absorption of water into the dosage form (80-84).
3.3.2.4. Binders
Also called as adhesives, are added to the tablet formulation to ensure the required strength to compact the powder, and is used in very low amounts (1% - 2%) (58, 85).
3.3.2.5. Lubricants
Lubricants are used to lower the friction and adhesion between the tablet surface and die during tablet ejection (86, 87). Although, it should be noted that hydrophobic lubricants such as calcium or magnesium stearate may delay the disintegration of the fast dissolving tablet; hence it is suggested to use hydrophilic lubricants such as sodium or potassium benzoate for these dosage forms (88).
3.3.2.6. Fillers
Filler is used to increase the bulk volume of the powder and the size of the tablet to form a tablet with suitable size for handling when the drug is very potent, (59).
3.4. Preparation Methods of FDS
Preparation of different FDS dosage forms vary from each other. The methods are shown in Table 2 and each method is then explained briefly. It should be noted that only some of these methods are commercialized for FDS preparation and other techniques are mostly used in researches.
Preparation Methods of Different Fast Dissolving Systems Dosage Forms
| Tablets (35, 37, 56, 59) | Films (32, 36, 60, 61) | Nanofibers (29, 89-92) |
|---|---|---|
| Freeze drying/lyophilization | Solvent casting | Drawing |
| Spray drying | Semi-solid casting | Template synthesis |
| Molding | Hot melt extrusion | Phase separation |
| Sublimation | Rolling | Self-assembly |
| Mass extrusion | Solid dispersion extrusion | Electrospinning |
| Direct compression | Compaction |
3.4.1. Tablet Preparation
3.4.1.1. Lyophilization
The process of drying at low temperature by sublimation technique gives the tablets a highly porous structure. It is also useful for heat sensitive drugs (48, 93-95).
3.4.1.2. Spray Drying
An aqueous solution containing the drug, a specific matrix and other excipients is sprayed to make a fine powder by vaporizing the solvent. The resulted fine particles are then compressed into tablets (96).
3.4.1.3. Molding
It contains preparation of a suspension or moist powder followed by compression and drying in molded plates, giving the tablet a less compact and porous structure (97, 98).
3.4.1.4. Sublimation
Is a technique to remove subliming material by sublimation from the compressed tablets giving it high porosity and rapid dissolution in saliva (37, 95-98).
3.4.1.5. Mass Extrusion
In this technique the ingredients are blended together, making a moist mixture, then driven out through the extruder to form cylindrical extrudates witch can be cut into tablets (99).
3.4.1.6. Direct Compression
It is a fast and simple technique in tablet manufacturing. The powder blend is compressed by the tableting machine to form tablets in different sizes and shapes without the need to granulation process (100-103). This technique may be the final stage of other methods to prepare tablets.
3.4.2. Film Preparation
3.4.2.1. Solvent Casting
In this technique the drug and all of the water soluble excipients are dissolved in a solvent to form a homogenous viscous solution which is then poured into a plate and dried. In some cases the water soluble and water insoluble ingredients can be dissolved in specific solvents separately and then the two solutions can be mixed (6, 104, 105). Fast dissolving films of maltodextrin and verapamil (4, 106) and fast dissolving films of meclizine (107) were made by this technique.
3.4.2.2. Semi-Solid Casting
A plasticizer and an acid insoluble polymer solution are added to a solution of water soluble polymer, thus forming a gel which is casted into films by heat controlled drums (34, 62, 104).
3.4.2.3. Hot Melt Extrusion
It is the process of applying heat and pressure to a molten polymer and extruding it through an orifice in a continuous process. This process is mostly used to make granules, tablets, transdermal and transmucosal delivery systems (36, 108, 109). The method is used to make fast dissolving films of maltodextrin (4).
3.4.2.4. Rolling
Two premix solutions containing a film forming polymer, a polar solvent and other excipients are made. API is added to one solution, and then all the solutions are poured into the feed tank and mixed together. After that, the mixed solution is carried away by a roller and dried to form a film using bottom drying (34, 62).
3.4.2.5. Solid Dispersion
The drug and hydrophilic polymers are dissolved or dispersed in a solvent and left to dry in the shape of films. The resulted films consist of an amorphous carrier which its drug molecules or particles are dispersed homogenously in the matrix. This method is used to make fast dissolving acetaminophen films (110-114).
3.4.2.6. Compaction
The method is commonly used as a dry granulation technique in the pharmaceutical industry to produce tablets with ingredients sensitive to heat and moisture. This method is mostly used to make matrix films from two different polymers (115, 116).
3.4.3. Nanofiber Preparation
There are different methods to prepare nanofibers (Table 2). However the electrospinning technique is a promising method to prepare nanofibers in research and industry. Nanofibers prepared by electrospinning are the most suitable choices to improve dissolution and hence bioavailability of drugs and the method has gained attention due to its efficacy and advantages over traditional preparation technologies (39, 117). The following part focuses on this method of preparation (28, 29, 69).
3.4.3.1. Electrospinning Method
In the electrospinning process, a high voltage power supply (118) is used to provide a desirable voltage between the solution and the collector (28, 119). Spinning solutions are carefully loaded into a syringe attached to a stainless steel capillary metal-hub needle (28) and the specific feed rate of the solution is maintained to avoid air bubbles. The positive electrode of the high voltage power supply is connected to the needle tip (117). The earthed electrode is connected to a metal collector (29). Collectors have different sizes and shapes due to their application. Increasing the voltage between the two electrodes induces a tailor cone formation at the tip of the needle and at a specific voltage (89), depending on the concentration and type of polymer, the solution exits the needle tip as a fiber jet and is shot toward the collector (28), thinning of the fibers to nanosize and drying by solvent evaporation take place on the way to the collector (118-120). Sometimes the melted polymer solutions can be used and the film is solidified by cooling on the way to the collector (39, 121, 122). The distance between the needle tip and collector, the voltage and the feed rate of the syringe have to be adjusted to obtain a suitable fiber jet and proper nanofibers (43, 118). Electrospun nanofibers are usually collected as a film or strip and can be developed in various sizes and shapes according to their administration (39, 117, 122).
3.5. Special Advantages of Electrospun Nanofibers
Electrospinning process is preferred to prepare nanofibers due to its efficiency and simplicity in fabrication, versatility in manufacturing different drugs and polymers, low cost of production and possibility to scale up to the industrial level (121, 123).
Electrospun nanofibers have a large surface area that leads to fast dissolution and/or disintegration of the film (85). These nanofiber films have merged the stability of solid dosage forms with the bioavailability of liquid forms because of high surface area to volume ratio (118) which enhances fast dissolution and high solubility. A very useful advantage is the ability to be manufactured using just an API and polymer (111, 124), thus reducing any side effects of excipients and lowering the cost of production. For the process of electrospinning, crystallized or amorphous drugs can be used, but researches show that even crystallized drugs turn into amorphous state through the electrospinning process, because of fast solvent evaporation which gives the drug no time to crystal growth and making them more likely to dissolve rapidly (39, 120).
In addition to the benefits of electrospinning, nanofibers prepared by this technique also have some specific advantages. Drugs in the nanofiber structures have a faster permeation rate across oral mucosa (117). They can also be used to treat localized conditions in oral cavity due to their mucoadhesive property (125) as well as systemic absorption (28, 29). Encapsulating drugs as nanofibers enhances the bioavailability of drugs due to faster disintegration and dissolution (45, 126, 127). Furthermore, insoluble or swellabe polymers are used in nanofibers to control the drug release (42, 120). Using other drug delivery systems such as nanoparticles or microemulsions in combination with nanofibers are also under study (70, 119).
3.6. Evaluation of Fast Dissolving Systems
Although the evaluation techniques for tablets are different from films and nanofibers, the main ideas are the same. However explaining all of the evaluation methods is far from the scope of this review, they are only mentioned briefly in Table 3 (32, 34, 36, 45, 47).
Evaluation Methods of Fast Dissolving Systems
| Tablets | Films and Nanofibers |
|---|---|
| Taste/ Mouth sensation | Morphology study (31) |
| Tablet thickness | Organoleptic evaluation |
| Taste/ mouth sensation | Thickness |
| Tablet thickness | Mechanical properties |
| Hardness | Tensile strength |
| Crushing strength | Tear resistance |
| Elastic modulus | |
| Percentage elongation | |
| Folding endurance | |
| Water absorption ratio | Swelling property |
| Disintegration time (47) | Disintegration time |
| Dissolution test (31, 128) | Dissolution test (110) |
| Wetting time | |
| Friability | Fiber diameter (only for nanofibers) (3, 29, 89) |
| Uniformity of dispersion |
The FDS evaluation tests in some cases need special conditions or modifications compared to the traditional dosage forms; for example due to the fast dissolution and disintegration of FDS, the test procedures should be filmed by a high speed camera to make it possible to determine the time of dissolution and disintegration. Also for films and nanofibers, a low volume media are used for dissolution test (5 - 10 mL). Table 4 shows the dissolution and disintegration time for different FDS dosage forms (28, 29, 42)).
Disintegration and Dissolution Time of Fast Dissolving Systems Dosage Forms
4. Conclusions
Nowadays, patients are looking for rapid effect of medications (40, 45) and due to the difficulties and bad compliance of injectable dosage forms, they prefer to use rapid acting oral dosage forms (27). Oral fast delivery systems are the most convenient forms for fast drug delivery (3, 39). They are available in different types of dosage forms (47), and are developing in order to improve effectiveness, feasibility, ease of production and administration (111). As shown in Table 4, nanofibers have the fastest dissolution time among different fast dissolving systems, which is due to their very high porosity (28, 29). Thus they can be used as novel drug delivery systems for fast dissolving purposes (131).
Acknowledgements
References
-
1.
Jain K, Awasthi S, Kumar P, Somashekariah BV, Phani AR. Formulation and Pharmacokinetic Studies of Rapidly Dissolving Nanofibers. Middle-East J Sci Res. 2014;22(8):1176-80.
-
2.
Bera A, Mukherjee A. A Detailed Study of Mouth Dissolving Drug Delivery System. Acta Chim Pharm Indica. 2013;3(1):65-93.
-
3.
Illangakoon UE, Nazir T, Williams GR, Chatterton NP. Mebeverine-loaded electrospun nanofibers: physicochemical characterization and dissolution studies. J Pharm Sci. 2014;103(1):283-92. [PubMed ID: 24258335]. https://doi.org/10.1002/jps.23759.
-
4.
Cilurzo F, Cupone IE, Minghetti P, Selmin F, Montanari L. Fast dissolving films made of maltodextrins. Eur J Pharm Biopharm. 2008;70(3):895-900. [PubMed ID: 18667164]. https://doi.org/10.1016/j.ejpb.2008.06.032.
-
5.
Chaudhary H, Gauri S, Rathee P, Kumar V. Development and optimization of fast dissolving oro-dispersible films of granisetron HCl using Box–Behnken statistical design. Bull Fac Pharm, Cairo Univ. 2013;51(2):193-201. https://doi.org/10.1016/j.bfopcu.2013.05.002.
-
6.
Hoffmann EM, Breitenbach A, Breitkreutz J. Advances in orodispersible films for drug delivery. Expert Opin Drug Deliv. 2011;8(3):299-316. [PubMed ID: 21284577]. https://doi.org/10.1517/17425247.2011.553217.
-
7.
Pathan IB, Shingare PR, Kurumkar P. Formulation design and optimization of novel mouth dissolving tablets for venlafaxine hydrochloride using sublimation technique. J P Res. 2013;6(6):593-8. https://doi.org/10.1016/j.jopr.2013.04.054.
-
8.
Yu DG, Shen XX, Branford-White C, White K, Zhu LM, Bligh SW. Oral fast-dissolving drug delivery membranes prepared from electrospun polyvinylpyrrolidone ultrafine fibers. Nanotechnology. 2009;20(5):55104. [PubMed ID: 19417335]. https://doi.org/10.1088/0957-4484/20/5/055104.
-
9.
Boateng JS, Auffret AD, Matthews KH, Humphrey MJ, Stevens HN, Eccleston GM. Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces. Int J Pharm. 2010;389(1-2):24-31. [PubMed ID: 20083177]. https://doi.org/10.1016/j.ijpharm.2010.01.008.
-
10.
El-Mahrouk GM, El-Gazayerly ON, Aboelwafa AA, Taha MS. Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: in vitro and in vivo performance. Int J Pharm. 2014;467(1-2):100-12. [PubMed ID: 24680961]. https://doi.org/10.1016/j.ijpharm.2014.03.049.
-
11.
Dinge A, Nagarsenker M. Formulation and evaluation of fast dissolving films for delivery of triclosan to the oral cavity. AAPS PharmSciTech. 2008;9(2):349-56. [PubMed ID: 18431674]. https://doi.org/10.1208/s12249-008-9047-7.
-
12.
Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev. 2005;57(11):1666-91. [PubMed ID: 16183164]. https://doi.org/10.1016/j.addr.2005.07.003.
-
13.
Vrbata P, Berka P, Stranska D, Dolezal P, Musilova M, Cizinska L. Electrospun drug loaded membranes for sublingual administration of sumatriptan and naproxen. Int J Pharm. 2013;457(1):168-76. [PubMed ID: 24050988]. https://doi.org/10.1016/j.ijpharm.2013.08.085.
-
14.
Seager H. Drug-delivery products and the Zydis fast-dissolving dosage form. J Pharm Pharmacol. 1998;50(4):375-82. [PubMed ID: 9625481].
-
15.
Cilurzo F, Minghetti P, Como A, Montanari L. Maltodextrin Fast–Dissolving Film: A Feasibility Study. Pharma Films Srl. Milano Italy: Pharma Films Srl; 2005. Available from: http://www.tecnova-srl.it/download/film.
-
16.
Shiv G, Ajay P, Prateek P, Sanket T, Deepu P, Pramod S, et al. Formulation and Evaluation of Fast Dissolving Tablet of Ziprasidone HCL. Am J Pharm Res. 2013;3(4).
-
17.
Reddy LH, Ghosh B. Fast dissolving drug delivery systems: A review of the literature. Ind j pharm ci. 2002;64(4):331-6.
-
18.
Sharma Ritika RM, Prakash P, Sharma S. Fast dissolving drug delivery system - a review. Int Res J Pharm. 2011;2(11):21-9.
-
19.
Y.A.Chowdary SM, Madhu-Babu M, Aparna K, Himabindu P. A Review on Fast Dissolving Drug Delivery Systems- A Pioneering Drug Delivery Technology. Bull Environ, Pharmacol Life Sci. 2012;1(12):8-20.
-
20.
Prajapati BG, Ratnakar N. A review on recent patents on fast dissolving drug delivery system. Int J PharmTech Res. 2009;1(3):790-8.
-
21.
Lindgren S, Janzon L. Prevalence of swallowing complaints and clinical findings among 50–79-year-old men and women in an urban population. Dysphagia. 1991;6(4):187-92. https://doi.org/10.1007/BF02493524.
-
22.
Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J Control Release. 2009;139(2):94-107. [PubMed ID: 19559740]. https://doi.org/10.1016/j.jconrel.2009.06.014.
-
23.
Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, et al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev. 2012;64(1):16-28. [PubMed ID: 21371513]. https://doi.org/10.1016/j.addr.2011.02.008.
-
24.
Yu DG, Zhou J, Chatterton NP, Li Y, Huang J, Wang X. Polyacrylonitrile nanofibers coated with silver nanoparticles using a modified coaxial electrospinning process. Int J Nanomedicine. 2012;7:5725-32. [PubMed ID: 23166437]. https://doi.org/10.2147/IJN.S37455.
-
25.
Lam JK, Xu Y, Worsley A, Wong IC. Oral transmucosal drug delivery for pediatric use. Adv Drug Deliv Rev. 2014;73:50-62. [PubMed ID: 23999459]. https://doi.org/10.1016/j.addr.2013.08.011.
-
26.
Gauri S, Kumar G. Fast dissolving drug delivery and its technologies. Drug Delivery Syst. 2012;7:8.
-
27.
Ignatious F, Sun L, Lee CP, Baldoni J. Electrospun nanofibers in oral drug delivery. Pharm Res. 2010;27(4):576-88. [PubMed ID: 20143253]. https://doi.org/10.1007/s11095-010-0061-6.
-
28.
Illangakoon UE, Gill H, Shearman GC, Parhizkar M, Mahalingam S, Chatterton NP, et al. Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning. Int J Pharm. 2014;477(1-2):369-79. [PubMed ID: 25455779]. https://doi.org/10.1016/j.ijpharm.2014.10.036.
-
29.
Li X, Kanjwal MA, Lin L, Chronakis IS. Electrospun polyvinyl-alcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin. Colloids Surf B Biointerfaces. 2013;103:182-8. [PubMed ID: 23201736]. https://doi.org/10.1016/j.colsurfb.2012.10.016.
-
30.
Zade PS, Kawtikwar PS, Sakarkar DM. Formulation, evaluation and optimization of fast dissolving tablet containing tizanidine hydrochloride. Int J Pharm Tech Res. 2009;1(1):34-42.
-
31.
Mashru RC, Sutariya VB, Sankalia MG, Parikh PP. Development and evaluation of fast-dissolving film of salbutamol sulphate. Drug Dev Ind Pharm. 2005;31(1):25-34. [PubMed ID: 15704855]. https://doi.org/10.1081/DDC-43947.
-
32.
Pandya Ketul KRP MR, Patel NM. Fast dissolving films: a novel approach to oral drug delivery. Asia J Pharm Sci Technol. 2013;3(1):25-31.
-
33.
Sharma R, Parikh RK, Gohel MC, Soniwala MM. Development of taste masked film of valdecoxib for oral use. Indian Journal of Pharmaceutical Sciences. 2007;69(2):320.
-
34.
Kathpalia H, Gupte A. An introduction to fast dissolving oral thin film drug delivery systems: a review. Curr Drug Deliv. 2013;10(6):667-84. [PubMed ID: 24274635].
-
35.
Chang RK, Xiaodi G, Burnside BA, Couch RA. Fast-dissolving tablets. Pharm technol. 2000;24(6):52-5.
-
36.
Juluru NS. Fast dissolving oral films: A review. Int. J Adv Pharm, Biol Chem. 2013;2(1):108-12.
-
37.
Arora P, Sethi VA. Orodispersible tablets: A comprehensive review. Int J Res Dev Pharm Life Sci. 2013;2(2):270-84.
-
38.
Heer D, Aggarwal G, Kumar SH. Recent trends of fast dissolving drug delivery system–an overview of formulation technology. Pharmacophore. 2013;4(1):1-9.
-
39.
Lopez FL, Shearman GC, Gaisford S, Williams GR. Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning. Mol Pharm. 2014;11(12):4327-38. [PubMed ID: 25317777]. https://doi.org/10.1021/mp500391y.
-
40.
Jiang H, Fang D, Hsiao B, Chu B, Chen W. Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes. J Biomater Sci Polym Ed. 2004;15(3):279-96. [PubMed ID: 15147162].
-
41.
Kouchak M, Azarpanah A. Preparation and In Vitro Evaluation of Chitosan Nanoparticles Containing Diclofenac Using the Ion-Gelation Method. Jundishapur J Nat Pharm Prod. 2015;10(2). ee23082. https://doi.org/10.17795/jjnpp-23082.
-
42.
Shen X, Yu D, Zhu L, Branford-White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit(R) L 100-55 nanofibers for colon-targeted drug delivery. Int J Pharm. 2011;408(1-2):200-7. [PubMed ID: 21291969]. https://doi.org/10.1016/j.ijpharm.2011.01.058.
-
43.
Nagy ZK, Nyúl K, Wagner I, Molnár K, Marosi G. Electrospun water soluble polymer mat for ultrafast release of Donepezil HCl. Express Polym Lett. 2010;4(12):763-72.
-
44.
Lakshmi PK, Lavanya D, Ali MMH. Effect of synthetic super disintegrants and natural polymers in the preparation of donepezil hydrochloride fast disintegration films. 2014. 2014;3(3):4. https://doi.org/10.3329/icpj.v3i3.17892.
-
45.
Tayel SA, El Nabarawi MA, Amin MM, Abou Ghaly MH. Sumatriptan succinate sublingual fast dissolving thin films: formulation and in vitro/in vivo evaluation. Pharm Dev Technol. 2015:1-10. [PubMed ID: 25597782]. https://doi.org/10.3109/10837450.2014.1003655.
-
46.
Kenawy el R, Bowlin GL, Mansfield K, Layman J, Simpson DG, Sanders EH, et al. Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. J Control Release. 2002;81(1-2):57-64. [PubMed ID: 11992678].
-
47.
Siddiqui MDN, Garg G, Sharma PK. A Short Review on-A Novel Approach in Oral Fast Dissolving Drug Delivery System and Their Patents. Adv Biol Res. 2011;5(6):291-303.
-
48.
Mishra R, Amin A. Formulation development of taste-masked rapidly dissolving films of cetirizine hydrochloride. Pharm technol. 2009;33(2):48-56.
-
49.
Dzija MR, Barkalow DG, Chapdelaine AH, Zyck DJ. Edible film formulations containing maltodextrin. Google Patents; 2003.
-
50.
Prakash I, Dubois GE, Clos JF, Wilkens KL, Fosdick LE. Development of rebiana, a natural, non-caloric sweetener. Food Chem Toxicol. 2008;46 Suppl 7:S75-82. [PubMed ID: 18554769]. https://doi.org/10.1016/j.fct.2008.05.004.
-
51.
Kanekar H, Khale A. Coloring Agents: Current Regulatory Perspective for Coloring Agents Intended for Pharmaceutical & Cosmetic Use. Int J Pharm Phytopharmacol Res (eIJPPR). 2014;3(5):365-73.
-
52.
Allam KV, Kumar GP. Colorants–the cosmetics for the pharmaceutical dosage forms. Int J Pharm Pharm Sci. 2011;3(Suppl 3):9.
-
53.
Jia L, Qin XH. The effect of different surfactants on the electrospinning poly (vinyl alcohol)(PVA) nanofibers. J therm anal calorim. 2013;112(2):595-605.
-
54.
Aykut Y, Pourdeyhimi B, Khan SA. Effects of surfactants on the microstructures of electrospun polyacrylonitrile nanofibers and their carbonized analogs. J Appl Polymer Sci. 2013;130(5):3726-35. https://doi.org/10.1002/app.39637.
-
55.
Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315-499. [PubMed ID: 23383426].
-
56.
Bhowmik D, Chiranjib B, Krishnakanth P, Chandira RM. Fast dissolving tablet: an overview. J chem pharm res. 2009;1(1):163-77.
-
57.
Bandari S, Mittapalli RK, Gannu R, Rao YM. Orodispersible tablets: An overview. Asia j pharm. 2008;2(1):2.
-
58.
Patil PB, More VN, Tour NS. Recent trends in orodispersible tablets–An overview of formulation technology and future prospects. Int JPharm Sci Res. 2015;6(7):1056-66.
-
59.
McLaughlin R, Banbury S, Crowley K. Orally disintegrating tablets: the effect of recent FDA guidance on ODT technologies and applications. Pharm Technol. 2009;6.
-
60.
Patil PB, Shrivastava SK. Fast dissolving oral films: An innovative drug delivery system. Structure. 2012;20(70):50-500.
-
61.
Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. Int J Chem Tech Res. 2010;2(1):576-83.
-
62.
Pathare YS, Hastak VS, Bajaj AN. Polymers used for fast disintegrating oral films: A review. Int J Pharm Sci Rev Res. 2013;21(1):169-78.
-
63.
Chien MJ, Tirol G, Chien C, Schmitt R, editors. Film forming polymers in oral films. Poster presented at the 2006 Annual Meeting and Exposition of the American Association of Pharmaceutical Scientist Oct. pp. 1–5. 2006. p. 1-5.
-
64.
Cilurzo F, Minghetti P, Como A, Montanari L. Feasibility study of Fast Dissolving Film Containing Piroxicam. AAPS Pharm Sci Tech. 2005;7:52.
-
65.
Chen MJ, Tirol G, Bass C, Corniello CM, Watson G, Sanchez I. Castable edible pharmaceutical films. Drug Del Tech. 2008;8(6):35-41.
-
66.
Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res. 2002;60(4):613-21. [PubMed ID: 11948520].
-
67.
Kouchak M, Ameri A, Naseri B, Kargar Boldaji S. Chitosan and polyvinyl alcohol composite films containing nitrofurazone: preparation and evaluation. Iran J Basic Med Sci. 2014;17(1):14-20. [PubMed ID: 24592302].
-
68.
Bavarsad N, Kouchak M, Varmaziar M, Sadeghi-Nejad B. Preparation, Characterization and Evaluation of Antifungal Efficacy of Chitosan/Soy Phosphatidylcholine Topical Films Containing Griseofulvin. Jundishapur J Nat Pharm Prod. 2015;10(2). ee27562.
-
69.
Matthews JA, Wnek GE, Simpson DG, Bowlin GL. Electrospinning of collagen nanofibers. Biomacromolecules. 2002;3(2):232-8. [PubMed ID: 11888306].
-
70.
Li X, Su Y, Zhou X, Mo X. Distribution of Sorbitan Monooleate in poly(L-lactide-co-epsilon-caprolactone) nanofibers from emulsion electrospinning. Colloids Surf B Biointerfaces. 2009;69(2):221-4. [PubMed ID: 19131219]. https://doi.org/10.1016/j.colsurfb.2008.11.031.
-
71.
Xu CY, Inai R, Kotaki M, Ramakrishna S. Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials. 2004;25(5):877-86. [PubMed ID: 14609676].
-
72.
Saxena SK. Polyvinyl alcohol (PVA). Chem Tech Asses (CTA). 2004;61:3-7.
-
73.
Hassan CM, Peppas NA. Structure and applications of poly (vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. Biopolymers· PVA Hydrogels, Anionic Polymerisation Nanocomposites. Heidelberg, New York: Springer; 2000. p. 37-65.
-
74.
Casper CL, Yamaguchi N, Kiick KL, Rabolt JF. Functionalizing electrospun fibers with biologically relevant macromolecules. Biomacromolecules. 2005;6(4):1998-2007. [PubMed ID: 16004438]. https://doi.org/10.1021/bm050007e.
-
75.
Bühler V. Polyvinylpyrrolidone excipients for pharmaceuticals: Povidone, crospovidone and copovidone. New York: Springer Science & Business Media; 2005.
-
76.
Abdel-Hamid SM, Abdel-Hady SE, El-Shamy AH, El-Dessouky HF. A novel formulation for mebeverine hydrochloride. Drug Dev Ind Pharm. 2007;33(10):1078-89. [PubMed ID: 17882731]. https://doi.org/10.1080/03639040601180069.
-
77.
Garsuch V, Breitkreutz J. Comparative investigations on different polymers for the preparation of fast-dissolving oral films. J Pharm Pharmacol. 2010;62(4):539-45. [PubMed ID: 20604845]. https://doi.org/10.1211/jpp.62.04.0018.
-
78.
Sakellariou P, Rowe RC. Interactions in cellulose derivative films for oral drug delivery. Prog Polym Sci. 1995;20(5):889-942. https://doi.org/10.1016/0079-6700(95)00008-4.
-
79.
Banker GS. Film coating theory and practice. J Pharm Sci. 1966;55(1):81-9. [PubMed ID: 5918657].
-
80.
Balasubramaniam J, Bindu K, Rao VU, Ray D, Haldar R, Brzeczko AW. Effect of superdisintegrants on dissolution of cationic drugs. Dissolution Technol. 2008;15(2):18.
-
81.
Patil C, Das S. Effect of various superdisintegrants on the drug release profile and disintegration time of Lamotrigine orally disintegrating tablets. Afr j pharm pharmacol. 2011;5(1):76-82.
-
82.
Khairnar DA, Anantwar SP, Chaudhari CS, Shelke PA. Superdisintegrants: An emerging paradigm in orodispersible tablets. Int J Biopharm. 2014;5(2):119-28.
-
83.
Shihora H, Panda S. Superdisintegrants, utility in dosage forms: A quick review. J. Pharm. Sci. Biosci. Res. 2011;1(3):148-53.
-
84.
Rawat S, Derle DV, Fukte SR, Shinde PR, Parve BS. Superdisintegrants: An Overview. world J pharm pharm sci. 2014;3(5):263-78.
-
85.
Bompilwar MS, Gawai NM, Biyani KR. Formulation and Evaluation of Orodispersible Tablet of Metformin HCl. Int J Res Pharm Biomed Sci. 2013;4(3):782-7.
-
86.
Faldu B, Zalavadiya B. Lubricants: Fundamentals of Tablet Manufacturing. Int J Res Pharm Chem. 2012;2(4):921-5.
-
87.
Li J, Wu Y. Lubricants in pharmaceutical solid dosage forms. Lubricants. 2014;2(1):21-43.
-
88.
Alexander TA. 1998.Lubricants for use in tabletting.
-
89.
Greiner A, Wendorff JH. Electrospinning: a fascinating method for the preparation of ultrathin fibers. Angewandte ChemInt Ed. 2007;46(30):5670-703. https://doi.org/10.1002/anie.200604646.
-
90.
Zeng J, Xu X, Chen X, Liang Q, Bian X, Yang L, et al. Biodegradable electrospun fibers for drug delivery. J Controlled Release. 2003;92(3):227-31. https://doi.org/10.1016/S0168-3659(03)00372-9.
-
91.
Mellado P, McIlwee HA, Badrossamay MR, Goss JA, Mahadevan L, Parker KK. A simple model for nanofiber formation by rotary jet-spinning. Appl Phys Lett. 2011;99(20):203107.
-
92.
Li X, Lin L, Kanjwal MA, Chronakis IS, Liu S, Chen Y. Preparing photochromic nanofibers and animal cells using a photochromic compound of 1',3',3'-trimethyl-6-nitrospiro (2H-1-benzopyran-2,2'-indoline). Colloids Surf B Biointerfaces. 2012;89:67-72. [PubMed ID: 21924877]. https://doi.org/10.1016/j.colsurfb.2011.08.024.
-
93.
Sznitowska M, Płaczek M, Klunder M. The physical characteristics of lyophilized tablets containing a model drug in different chemical forms and concentrations. Acta Pol Pharm. 2004;62(1):25-9.
-
94.
Jones RJ, Rajabi-Siahboomi A, Levina M, Perrie Y, Mohammed AR. The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets. Pharmaceutics. 2011;3(3):440-57.
-
95.
Wagh MA, Kothawade DP, Salunkhe KS, Chavan NV, Daga VR. Techniques used in orally disintegrating drug delivery system. Int j drug delivery. 2010;2(2).
-
96.
Machimura H. Preparation of orally disintegrating tablet by co-spray drying F-melt and active ingredients. Fuji Chem Ind Pharm Tech Newsl. 2011;20:26-32.
-
97.
Mishra DN, Bindal M, Singh SK, Vijaya Kumar SG. Spray dried excipient base: a novel technique for the formulation of orally disintegrating tablets. Chem Pharm Bull (Tokyo). 2006;54(1):99-102. [PubMed ID: 16394558].
-
98.
Mangal-Mohit TN, Bansal R, Thakral S, Goswami M. Fast dissolving tablet: an approach for emergency treatment. Int J Res Ayurveda Pharm. 2012;3(3):377-80.
-
99.
Mohamed Mutahar BMD RK, Sateesha SB, Shahista O, Nargund LVG. Development of matrix tablets by extrusion/spheronization process using laboratory extruder: study of the effects of the process parameters. Int J Pharm Pharm Sci. 2010:204-14.
-
100.
Ali S, Santos C, editors. Crospovidone in development of directly compressible tablets. AAPS Annual Meeting and Exposition. 2009; Los Angeles, CA, USA.
-
101.
Dokala GK, Pallavi C. Direct compression-an overview. Intl J Res Pharm Biom Sci. 2013;4(1):155-8.
-
102.
Leesawat P, Laopongpaisan A, Sirithunyalug J. Optimization of Direct Compression Aspirin Tablet Using Statistical Mixture Design. CMU. J. 2004;3(2):97.
-
103.
Erum S, Hassan F, Hasan SMF, Jabeen S. Formulation of aspirin tablets using fewer excipients by direct compression. Pakistan J Pharmacol. 2011;28(1):31-7.
-
104.
Mishra R, Amin A. Quick API delivery. 2007.
-
105.
Abbaspour MR, Jalali S. Study of free-films and coated tablets based on hpmc and microcrystalline cellulose, aimed for improve stability of moisture-sensitive drugs. Jundishapur JNat Pharm Prod. 2007;2010(01, Winter):6-17.
-
106.
Kunte S, Tandale P. Fast dissolving strips: A novel approach for the delivery of verapamil. J Pharm Bioallied Sci. 2010;2(4):325-8. [PubMed ID: 21180465]. https://doi.org/10.4103/0975-7406.72133.
-
107.
Gupta MM, Patel MG, Kedawat M. Enhancement of dissolution rate of rapidly dissolving oral film of meclizine hydrochloride by complexation of Meclizine hydrochloride with ß-cyclodextrine. J Appl Pharm Sci. 2011;1(9):150-3.
-
108.
Low AQ, Parmentier J, Khong YM, Chai CC, Tun TY, Berania JE, et al. Effect of type and ratio of solubilising polymer on characteristics of hot-melt extruded orodispersible films. Int J Pharm. 2013;455(1-2):138-47. [PubMed ID: 23916824]. https://doi.org/10.1016/j.ijpharm.2013.07.046.
-
109.
Crowley M. M ZF, Repka MA, Thumma S, Upadhye SB, Battu SK, McGinity JW, et al. Hot Melt Extrusion. Technical Brief. 2007;3(2).
-
110.
Nagy ZK, Balogh A, Vajna B, Farkas A, Patyi G, Kramarics A, et al. Comparison of electrospun and extruded Soluplus(R)-based solid dosage forms of improved dissolution. J Pharm Sci. 2012;101(1):322-32. [PubMed ID: 21918982]. https://doi.org/10.1002/jps.22731.
-
111.
Yu DG, Branford-White C, White K, Li XL, Zhu LM. Dissolution improvement of electrospun nanofiber-based solid dispersions for acetaminophen. Am Assoc Pharm sci. 2010;11(2):809-17.
-
112.
Yu DG, Yang JM, Branford-White C, Lu P, Zhang L, Zhu LM. Third generation solid dispersions of ferulic acid in electrospun composite nanofibers. Int J Pharm. 2010;400(1):158-64.
-
113.
Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23-24):1068-75. [PubMed ID: 18061887]. https://doi.org/10.1016/j.drudis.2007.09.005.
-
114.
Liang AC, Chen LIH. Fast-dissolving intraoral drug delivery systems. Expert Opin Ther Pat. 2001;11(6):981-6. https://doi.org/10.1517/13543776.11.6.981.
-
115.
Ward IM, Hine PJ. The science and technology of hot compaction. Polymer. 2004;45(5):1413-27.
-
116.
Ramineni SK, Cunningham L. L JR, Dziubla TD, Puleo DA. Development of imiquimod-loaded mucoadhesive films for oral dysplasia. J Pharm Sci. 2013;102(2):593-603. [PubMed ID: 23192692]. https://doi.org/10.1002/jps.23386.
-
117.
Li C, Yu DG, Williams GR, Wang ZH. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process. PLoS One. 2014;9(3). ee92106. [PubMed ID: 24643072]. https://doi.org/10.1371/journal.pone.0092106.
-
118.
Gordon V, Marom G, Magdassi S. Formation of hydrophilic nanofibers from nanoemulsions through electrospinning. Int J Pharm. 2015;478(1):172-9. [PubMed ID: 25448579]. https://doi.org/10.1016/j.ijpharm.2014.11.038.
-
119.
Tonglairoum P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. Fabrication of a novel scaffold of clotrimazole-microemulsion-containing nanofibers using an electrospinning process for oral candidiasis applications. Colloids Surf B Biointerfaces. 2015;126:18-25. [PubMed ID: 25543979]. https://doi.org/10.1016/j.colsurfb.2014.12.009.
-
120.
Seif S, Franzen L, Windbergs M. Overcoming drug crystallization in electrospun fibers - Elucidating key parameters and developing strategies for drug delivery. Int J Pharm. 2015;478(1):390-7. [PubMed ID: 25448563]. https://doi.org/10.1016/j.ijpharm.2014.11.045.
-
121.
Vonch J, Yarin A, Megaridis CM. Electrospinning: A study in the formation of nanofibers. J Undergrad Res. 2007;1(1).
-
122.
Nagy ZK, Balogh A, Dravavolgyi G, Ferguson J, Pataki H, Vajna B, et al. Solvent-free melt electrospinning for preparation of fast dissolving drug delivery system and comparison with solvent-based electrospun and melt extruded systems. J Pharm Sci. 2013;102(2):508-17. [PubMed ID: 23161110]. https://doi.org/10.1002/jps.23374.
-
123.
Luo CJ, Stoyanov SD, Stride E, Pelan E, Edirisinghe M. Electrospinning versus fibre production methods: from specifics to technological convergence. Chem Soc Rev. 2012;41(13):4708-35. [PubMed ID: 22618026]. https://doi.org/10.1039/c2cs35083a.
-
124.
Sill TJ, von Recum HA. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials. 2008;29(13):1989-2006. [PubMed ID: 18281090]. https://doi.org/10.1016/j.biomaterials.2008.01.011.
-
125.
Murata Y, Isobe T, Kofuji K, Nishida N, Kamaguchi R. Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis. Pharmacol Pharm. 2013:325-30.
-
126.
Abbaspour M. Nanodrugs and natural pharmaceutical products. Jundishapur J Nat Pharm Prod. 2012;7(2):39-40. [PubMed ID: 24624151].
-
127.
Abbaspour M, Jalayer N, Sharif Makhmalzadeh B. Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadin by extrusion-spheronization. Adv Pharm Bull. 2014;4(2):113-9. [PubMed ID: 24511474]. https://doi.org/10.5681/apb.2014.018.
-
128.
Nishimura M, Matsuura K, Tsukioka T, Yamashita H, Inagaki N, Sugiyama T, et al. In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm. 2009;368(1-2):98-102. [PubMed ID: 18992311]. https://doi.org/10.1016/j.ijpharm.2008.10.002.
-
129.
Yasmeen BR, Firoz S, Mouli YC, Vikram A, Mahitha B, Aruna U. Preparation and evaluation of oral fast dissolving films of citalopram hydrobromide. Int J Biopharm. 2012;3(2):103-6.
-
130.
Jayjock MA. How much is enough to accept hormesis as the default? or 'At what point, if ever, could/should hormesis be employed as the principal dose-response default assumption in risk assessment?'. Hum Exp Toxicol. 2005;24(5):245-7. [PubMed ID: 16004187].
-
131.
Quan J, Yu Y, Branford-White C, Williams GR, Yu DG, Nie W, et al. Preparation of ultrafine fast-dissolving feruloyl-oleyl-glycerol-loaded polyvinylpyrrolidone fiber mats via electrospinning. Colloids Surf B Biointerfaces. 2011;88(1):304-9. [PubMed ID: 21798728]. https://doi.org/10.1016/j.colsurfb.2011.07.006.