Thin-film drug delivery uses a dissolving film or oral drug strip to administer
drugs via absorption in the mouth (
buccally or
sublingually) and/or via the small intestines (
enterically). A film is prepared using
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
polymers that rapidly dissolves on the tongue or buccal cavity,
delivering the drug to the
systemic circulation via
dissolution
Dissolution may refer to:
Arts and entertainment Books
* ''Dissolution'' (''Forgotten Realms'' novel), a 2002 fantasy novel by Richard Lee Byers
* ''Dissolution'' (Sansom novel), a 2003 historical novel by C. J. Sansom Music
* Dissolution, in mu ...
when contact with
liquid is made.
Thin-film drug delivery has emerged as an advanced alternative to the traditional
tablets,
capsules and liquids often associated with
prescription and
OTC medications. Similar in size, shape and thickness to a
postage stamp
A postage stamp is a small piece of paper issued by a post office, postal administration, or other authorized vendors to customers who pay postage (the cost involved in moving, insuring, or registering mail), who then affix the stamp to the f ...
, thin-film strips are typically designed for
oral administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...
, with the user placing the strip on or under the tongue (sublingual) or along the inside of the cheek (buccal). These drug delivery options allow the medication to bypass the first pass metabolism thereby making the medication more bioavailable. As the strip dissolves, the drug can enter the blood stream enterically, buccally or sublingually. Evaluating the systemic
transmucosal drug delivery, the
buccal mucosa
The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
is the preferred region as compared to the sublingual mucosa.
Different buccal delivery products have been marketed or are proposed for certain diseases like
trigeminal neuralgia
Trigeminal neuralgia (TN or TGN), also called Fothergill disease, tic douloureux, or trifacial neuralgia is a long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor functions such as ...
,
Ménière's disease
Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initi ...
,
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, and
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
. There are many commercial non-drug product to use thin films like Mr. Mint and
Listerine PocketPaks
breath freshening strips. Since then, thin-film products for other breath fresheners, as well as a number of cold, flu, anti-snoring and gastrointestinal medications, have entered the marketplace. There are currently several projects in development that will deliver prescription drugs using the thin-film
dosage form
Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a ca ...
.
Formulation of oral drug strips involves the application of both aesthetic and performance characteristics such as strip-forming polymers,
plasticizers
A plasticizer ( UK: plasticiser) is a substance that is added to a material to make it softer and more flexible, to increase its plasticity, to decrease its viscosity, and/or to decrease friction during its handling in manufacture.
Plastic ...
, active pharmaceutical ingredient, sweetening agents,
saliva stimulating agent, flavoring agents, coloring agents, stabilizing and thickening agents. From the regulatory perspectives, all
excipient
An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...
s used in the formulation of oral drug strips should be approved for use in oral pharmaceutical
dosage forms.
Oral drug strip development
Strip forming polymers
The polymer employed should be non-toxic, non-irritant and devoid of leachable impurities. It should have good wetting and spreadability property. The polymer should exhibit sufficient peel, shear and tensile strengths. The polymer should be readily available and should not be very expensive. Film obtained should be tough enough so that there won't be any damage while handling or during transportation. Combination of
microcrystalline
A microcrystalline material is a crystallized substance or rock that contains small crystals visible only through microscopic examination. There is little agreement on the range of crystal sizes that should be regarded as microcrystalline, but th ...
cellulose
Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell w ...
and
maltodextrin
Maltodextrin is a polysaccharide that is used as a food ingredient. It is produced from vegetable starch by partial hydrolysis and is usually found as a white hygroscopic spray-dried powder. Maltodextrin is easily digestible, being absorbed as ...
has been used to formulate Oral Strips of piroxicam made by hot melt extrusion technique.
Pullulan
Pullulan is a polysaccharide polymer consisting of maltotriose units, also known as α-1,4- ;α-1,6- glucan'. Three glucose units in maltotriose are connected by an α-1,4 glycosidic bond, whereas consecutive maltotriose units are connected to e ...
has been the most widely used film former (used in Listerine PocketPak, Benadryl, etc.)
Plasticizers
Plasticizer is a vital ingredient of the OS formulation. It helps to improve the flexibility and reduces the brittleness of the strip. Plasticizer significantly improves the strip properties by reducing the glass transition temperature of the polymer.
Glycerol
Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
,
Propylene glycol
Propylene glycol (IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH.
Containing two alcohol groups, it is classed as a diol. It i ...
, low molecular weight
polyethylene glycols
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular we ...
,
phthalate
Phthalates (, ), or phthalate esters, are esters of phthalic acid. They are mainly used as plasticizers, i.e., substances added to plastics to increase their flexibility, transparency, durability, and longevity. They are used primarily to soften ...
derivatives like
dimethyl,
diethyl and
dibutyl phthalate
Dibutyl phthalate (DBP) is an organic compound which is commonly used as a plasticizer because of its low toxicity and wide liquid range. With the chemical formula C6H4(CO2C4H9)2, it is a colorless oil, although commercial samples are often yell ...
,
Citrate
Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
derivatives such as tributyl, triethyl, acetyl citrate,
triacetin
Triacetin, is the organic compound with the formula . It is classified as a triglyceride, i.e., the triester of glycerol. It is a colorless, viscous, and odorless liquid with a high boiling point and a low melting point. It has a mild, sweet tast ...
and
castor oil
Castor oil is a vegetable oil pressed from castor beans.
It is a colourless or pale yellow liquid with a distinct taste and odor. Its boiling point is and its density is 0.961 g/cm3. It includes a mixture of triglycerides in which about ...
are some of the commonly used plasticizer excipients.
Active pharmaceutical ingredient
Since the size of the dosage form has limitation, high-dose molecules are difficult to be incorporated in OS. Generally 5%w/w to 30%w/w of active pharmaceutical ingredients can be incorporated in the oral strip.
Sweetening, flavoring and coloring agents
An important aspect of thin film drug technology is its taste and color. The sweet taste in formulation is more important in case of
pediatric
Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until the ...
population. Natural sweeteners as well as artificial sweeteners are used to improve the flavor of the mouth dissolving formulations for the flavors changes from individual to individual. Pigments such as titanium dioxide is incorporated for coloring.
Stabilizing and thickening agents
The stabilizing and thickening agents are employed to improve the
viscosity
The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water.
Viscosity quantifies the inte ...
and consistency of dispersion or solution of the strip preparation solution or suspension before casting. Drug content uniformity is a requirement for all dosage forms, particularly those containing low dose highly potent drugs. To uniquely meet this requirement, thin film formulations contain uniform dispersions of drug throughout the whole manufacturing process. Since this criterion is essential for the quality of the thin film and final pharmaceutical dosage form, the use of Laser Scanning Confocal Microscopy (LSCM) was recommended to follow the manufacturing process.
Oral strips in development
An increasing number of film-based therapeutics are in development, including:
*
Montelukast
Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Ot ...
indicated for the treatment of dementia, asthma and allergy, is being developed variously for uses as a film by IntelGenx and Aquestive Therapeutics (formerly known as Monosol Rx).
* Midatech, a company specializing in nanotechnology, is partnering with Aquestive Therapeutics to create a film-based insulin. (Sachs Associates. 5th Annual European Life Science CEP Forum for Partnering and Investing. March 6–7, 2012. Zurich, Switzerland.)
*
Rizatriptan
Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches. It is taken by mouth.
Common side effects include chest pain, dizziness, dry mouth, and tingling. Other side effects may ...
indicated for the treatment of migraine, is being developed for use as a film by IntelGenx, Aquestive Therapeutics, and Zim Laboratories Ltd.
* Aquestive Therapeutics is also developing a testosterone film-based therapeutic for the treatment of male hypogonadism. The product is currently in phase 1.
* Undergraduate
biomedical engineering
Biomedical engineering (BME) or medical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes (e.g., diagnostic or therapeutic). BME is also traditionally logical sciences ...
students at
Johns Hopkins University
Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hemisphere. It consi ...
have created a new drug delivery system based on the thin-film technology used by a breath freshener. Laced with a
vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. against
rotavirus
''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus ...
, the strips could be used to provide the vaccine to infants in impoverished areas.
Other molecules like Sildenafil citrate, Tadalafil, Methylcobalamin and Vitamin D3 are also developed by IntelGenx Zim Laboratories Ltd.
References
*
*
*
External links
How do you want your cold medicine? – ''Associated Press'' (10/10/05)
{{DEFAULTSORT:Thin Film Drug Delivery
Drug delivery devices
Dosage forms
Thin films