Thin-film drug delivery

Last updated

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 polymers that rapidly dissolves on the tongue or buccal cavity, delivering the drug to the systemic circulation via dissolution when contact with liquid is made.

Contents

Zuplenz 8 mg (approved by FDA, July 7, 2010). Photo courtesy of Aquestive Therapeutics (formerly MonoSol Rx). Zuplenz - 8mg.jpg
Zuplenz 8 mg (approved by FDA, July 7, 2010). Photo courtesy of Aquestive Therapeutics (formerly MonoSol Rx).

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, thin-film strips are typically designed for oral administration, 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.[ citation needed ] As the strip dissolves, the drug can enter the blood stream enterically, buccally or sublingually. Evaluating the systemic transmucosal drug delivery, the buccal mucosa 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, Ménière's disease, diabetes, and addiction.[ citation needed ] 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[ when? ] several projects in development that will deliver prescription drugs using the thin-film dosage form. [1]

Formulation of oral drug strips involves the application of both aesthetic and performance characteristics such as strip-forming polymers, plasticizers, active pharmaceutical ingredient, sweetening agents, saliva stimulating agent, flavoring agents, coloring agents, stabilizing and thickening agents. From the regulatory perspectives, all excipients 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 cellulose and maltodextrin has been used to formulate Oral Strips of piroxicam made by hot melt extrusion technique. Pullulan 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, Propylene glycol, low molecular weight polyethylene glycols, phthalate derivatives like dimethyl, diethyl and dibutyl phthalate, Citrate derivatives such as tributyl, triethyl, acetyl citrate, triacetin and castor oil 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. [2]

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 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 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. [3] 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. [4]

Oral strips in development

An increasing number of film-based therapeutics are in development, including:

Other molecules like sildenafil citrate, tadalafil, methylcobalamin and vitamin D3 are also developed by IntelGenx Zim Laboratories Ltd.

Related Research Articles

<span class="mw-page-title-main">Tablet (pharmacy)</span> Drug delivery form in which the ingredients are solidified for later consumption

A tablet is a pharmaceutical oral dosage form or solid unit dosage form. Tablets may be defined as the solid unit dosage form of medication with suitable excipients. It comprises a mixture of active substances and excipients, usually in powder form, that are pressed or compacted into a solid dose. The main advantages of tablets are that they ensure a consistent dose of medicine that is easy to consume.

<span class="mw-page-title-main">Route of administration</span> Path by which a drug, fluid, poison, or other substance is taken into the body

In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.

<span class="mw-page-title-main">Transdermal patch</span> Adhesive patch used to deliver medication through the skin

A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medication delivery is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered by this method. The first commercially available prescription patch was approved by the U.S. Food and Drug Administration in December 1979. These patches administered scopolamine for motion sickness.

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, or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerns such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors. A comprehensive classification system based on structure-property-application relationships has been proposed for excipients used in parenteral medications.

<span class="mw-page-title-main">Zydis</span>

Zydis is a technology used to manufacture orally disintegrating tablets developed by R.P. Scherer Corporation. Zydis tablets dissolve in the mouth within 3 seconds.

An enteric coating is a polymer barrier applied to oral medication that prevents its dissolution or disintegration in the gastric environment. This helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental effects of the drug, or to release the drug after the stomach. Some drugs are unstable at the pH of gastric acid and need to be protected from degradation. Enteric coating is also an effective method to obtain drug targeting. Other drugs such as some anthelmintics may need to reach a high concentration in a specific part of the intestine. Enteric coating may also be used during studies as a research tool to determine drug absorption. Enteric-coated medications pertain to the "delayed action" dosage form category. Tablets, mini-tablets, pellets and granules are the most common enteric-coated dosage forms.

<span class="mw-page-title-main">Capsule (pharmacy)</span> Relatively stable shell containing medicine

In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are:

Sublingual, from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Dosage forms 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, and apportioned into a particular dose. For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250 mg chewable tablets. The term unit dose can also sometimes encompass non-reusable packaging as well, although the FDA distinguishes that by unit-dose "packaging" or "dispensing". Depending on the context, multi(ple) unit dose can refer to distinct drug products packaged together, or to a single drug product containing multiple drugs and/or doses. The term dosage form can also sometimes refer only to the pharmaceutical formulation of a drug product's constituent drug substance(s) and any blends involved, without considering matters beyond that. Because of the somewhat vague boundaries and unclear overlap of these terms and certain variants and qualifiers within the pharmaceutical industry, caution is often advisable when conversing with someone who may be unfamiliar with another person's use of the term.

<span class="mw-page-title-main">Orally disintegrating tablet</span> Pill that dissolves on contact with saliva

An orally disintegrating tablet or orally dissolving tablet (ODT) is a drug dosage form available for a limited range of over-the-counter (OTC) and prescription medications. ODTs differ from traditional tablets in that they are designed to be dissolved on the tongue rather than swallowed whole. The ODT serves as an alternative dosage form for patients who experience dysphagia or for where compliance is a known issue and therefore an easier dosage form to take ensures that medication is taken. Common among all age groups, dysphagia is observed in about 35% of the general population, as well as up to 60% of the elderly institutionalized population and 18-22% of all patients in long-term care facilities ODTs may have a faster onset of effect than tablets or capsules, and have the convenience of a tablet that can be taken without water. During the last decade, ODTs have become available in a variety of therapeutic markets, both OTC and by prescription.

Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.

Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body.

Mucoadhesion describes the attractive forces between a biological material and mucus or mucous membrane. Mucous membranes adhere to epithelial surfaces such as the gastrointestinal tract (GI-tract), the vagina, the lung, the eye, etc. They are generally hydrophilic as they contain many hydrogen macromolecules due to the large amount of water within its composition. However, mucin also contains glycoproteins that enable the formation of a gel-like substance. Understanding the hydrophilic bonding and adhesion mechanisms of mucus to biological material is of utmost importance in order to produce the most efficient applications. For example, in drug delivery systems, the mucus layer must be penetrated in order to effectively transport micro- or nanosized drug particles into the body. Bioadhesion is the mechanism by which two biological materials are held together by interfacial forces. The mucoadhesive properties of polymers can be evaluated via rheological synergism studies with freshly isolated mucus, tensile studies and mucosal residence time studies. Results obtained with these in vitro methods show a high correlation with results obtained in humans.

<span class="mw-page-title-main">Oral administration</span> Route of administration where a substance is taken through the mouth

Oral administration is a route of administration whereby a substance is taken through the mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications.

Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism.

Orexo is a Swedish pharmaceutical company that develops improved pharmaceuticals based on innovative formulation technologies that meet large medical needs. Through presence in the US market, drugs and digital therapies are commercialized to treat opioid use disorder and adjacent diseases. Products targeting other therapeutic areas are developed and commercialized worldwide with partners.

A film coating is a thin polymer-based coat that is typically sprayed onto solid pharmaceutical dosage forms, such as tablets, capsules, pellets or granules. Film coating can impact both its appearance and its pharmacokinetics making it an essential process in making the final drug product.

Joseph Fuisz is an American attorney, inventor, and entrepreneur of Slovenian descent. He works predominantly in the pharmaceutical industry as the founder of Fuisz Pharma LLC. As of October 2015, he is named on 32 medical patents, and over forty patents.

Topical gels are a topical drug delivery dosage form commonly used in cosmetics and treatments for skin diseases because of their advantages over cream and ointment. They are formed from a mixture of gelator, solvent, active drug, and other excipients, and can be classified into organogels and hydrogels. Drug formulation and preparation methods depend on the properties of the gelators, solvents, drug and excipients used.

References

  1. "Oral Thin Films," in Orally Disintegrating Tablet and Film Technologies, 5th ed. (Technology Catalysts International, Falls Church, VA, 2008)
  2. Dixit, R.; Puthli, S. (2009). "Oral strip technology: Overview and future potential". Journal of Controlled Release. Mumbai,India. 139 (2): 94–107. doi:10.1016/j.jconrel.2009.06.014. PMID   19559740.
  3. "FDA Office of Regulatory Affairs, Sec. 460.600 Content Uniformity Testing of Tablets and Capsules". Fda.gov. Retrieved 2009-09-21.
  4. Le Person, S; Puiggali, J.R.; Baron, M.; Roques, M. (1998). "Near infrared drying of pharmaceutical thin films: experimental analysis of internal mass transport" (PDF). Chem. Eng. & Processing. 37 (3): 257–263. doi:10.1016/S0255-2701(98)00032-4.
  5. "Drug Delivery Via Dissolving Strips". Drug Discovery & Development. 10 (7): 10. 2007. ISSN   1524-783X.