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Home , Bioadhesive, Drug delivery, Oral administration, Route of administration

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701

______Review Article An Overview on: Sublingual Route for Systemic Delivery

K. Patel Nibha1 and SS. Pancholi2*

1Department of Pharmaceutics, BITS Institute of , Gujarat Technological university, Varnama, Vadodara, Gujarat, India 2BITS Institute of Pharmacy, Gujarat Technological University, Varnama, Vadodara, Gujarat, India. ______ABSTRACT Oral mucosal is an alternative and promising method of systemic drug delivery which offers several advantages. Sublingual literally meaning is ''under the '', administrating substance via mouth in such a way that the substance is rapidly absorbed via vessels under tongue. Sublingual route offers advantages such as bypasses hepatic first pass metabolic process which gives better , rapid , patient compliance , self-medicated. Dysphagia (difficulty in swallowing) is common among in all ages of people and more in pediatric, geriatric, psychiatric patients. In terms of permeability, sublingual area of oral cavity is more permeable than buccal area which is in turn is more permeable than palatal area. Different techniques are used to formulate the sublingual dosage forms. Sublingual drug administration is applied in field of cardiovascular , steroids, enzymes and some barbiturates. This review highlights advantages, disadvantages, different sublingual formulation such as tablets and films, evaluation.

Key Words: Sublingual delivery, techniques, improved bioavailability, evaluation.

INTRODUCTION and direct access to systemic circulation, the oral Drugs have been applied to the mucosa for topical mucosal route is suitable for drugs, which are application for many years. However, recently susceptible to acid hydrolysis in the or there has been interest in exploiting the oral cavity which are extensively metabolized in the liver. The as a portal for delivering drugs to the systemic continuous secretion of saliva results in rapid circulation. Notwithstanding the relatively poor removal of released drug and this may desire that permeability characteristics of the epithelium, a the oral cavity be restricted to the delivery of drugs, number are offered by this . which have a short systemic circulation. The mucin Foremost among these are the avoidance of first- film, which exists on the surface of the oral mucosa pass , ease of access to the delivery site, may provide an opportunity to retain a drug and the opportunity of sustained drug delivery delivery system in contact with the mucosa for predominantly via the buccal tissues prolonged periods if it is designed to be Oral mucosal drug delivery is an alternative mucoadhesive. Such system ensures a close contact method of systemic drug delivery that offers with absorbing membrane, thus optimizing the drug several advantages over both injectable and enteral concentration gradient across the biological methods. Because the oral mucosa is highly membrane and reducing the differential pathway. vascularised, drugs that are absorbed through the The oral mucosa may be potential site for oral mucosa directly enter the systemic circulation, controlled or sustained drug delivery. Oral route is by passing the and first-pass most preferred route by medical practitioners and metabolism in the liver. For some drugs, this manufacturer due to highest acceptability of results in rapid onset of action via a more patients. About 60% of all dosage forms available comfortable and convenient delivery route than the are the oral . The lower intravenous route. Not all drugs, however, can be bioavailability, long onset time and dysphagia administered through the oral mucosa because of patients turned the manufacturer to the parenterals the characteristics of the oral mucosa and the and orals. But the liquid orals (, physicochemical properties of the drug1. , etc) have the problem of The oral route of administration is considered as accurate dosing mainly and parenterals are painful the most widely accepted route. The unique drug delivery, so most patient incompliance2. environment of the oral cavity offers its potential as The target sites for local drug delivery in the oral a site for drug delivery. Because rich blood supply cavity include the following: Buccal, Sublingual,

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Periodontal region, Tongue, Gum. Other desirable also affected by the physicochemical properties of targeting sites adjacent to oral cavity include the drug to be delivered7. pharynx, larynx, adenoids and tonsils. Within the Sublingual products have been developed for oral cavity, delivery of drugs via the membranes of numerous indications ranging from migraines (for the oral cavity is classified into three categories: which rapid onset of action is important) to mental i) Sublingual delivery illness (for which patient compliance is important which is systemic delivery of drugs through the for treating chronic indications such as depression mucosal membranes lining the floor of the mouth and .)8 to the systemic circulation; ii) Buccal delivery Advantages which is drug administration through the mucosal • Ease of administration to patients who refuse membranes lining the and the area between to swallow a , such as pediatric, geriatric the and upper and lower lips to the systemic patients and psychiatric patients. circulation. • Convenience in administration of drug and iii) Local delivery accurate dosing as compared to liquid formulations. which is drug delivery to periodontal, gingival, • is not required for swallowing the delivery for the local treatment of ulcers, bacterial dosage form, which is convenient feature for and fungal and periodontal disease. patients who are traveling and do not have Sublingual administration of the drug means immediate access to water. placement of the drug under the tongue and drug • Good mouth feels property helps to change the reaches directly into the blood stream through basic view of as "bitter pill", ventral surface of the tongue and floor of the particularly for pediatric patients. mouth. The drug solutes are rapidly absorbed into • Fast dissolution of medicament and the reticulated which lies underneath the oral which will leads to rapid, onset of action. mucosa, and transported through the facial , • Some drugs are absorbed from the mouth internal jugular vein, and braciocephalic vein and pharynx and esophagus as the saliva passes down then drained in to systemic circulation.3 into the stomach, in such cases bioavailability of The sublingual route usually produces a faster drugs is increased. onset of action than orally ingested tablets and the • It provides advantages of liquid formulations portion absorbed through the sublingual blood in the form of solid dosage form. vessels bypasses the hepatic first-pass metabolic • Pregastric absorption can result in improved processes4-6 . The main mechanism for the bioavailability and as a result of reduced dosage, absorption of the drug in to oral mucosa is via improved clinical performance through a reduction passive diffusion into the lipoidal membrane. of unwanted effects. The absorption of the drug through the sublingual route is 3 to 10 times greater than oral route and is Disadvantage only surpassed by hypodermic . For these  Since sublingual administration of drugs formulations, the small volume of saliva is usually interferes with , drinking, and talking, this sufficient to result in tablet disintegration in the route is generally considered unsuitable for oral cavity. Sublingual absorption is mostly rapid prolonged administration. in action, but also short acting in duration.  Although this site is not well suited to Nitroglycerine, for example, is an effective sustained‐delivery systems. antianginal drug but is extensively metabolized  Sublingual medication cannot be used when taken orally (>90%). It is rapidly absorbed when a patient is uncooperative or unconscious. through the sublingual mucosa, and its peak plasma  The patient should not smoke while taking level is reached within 1‐2 min. Because of its sublingual medication, because causes short biological half life (3‐5 min.), however the of the blood vessels. This will blood concentration of nitroglycerine declines decrease the absorption of the medication. rapidly to a level below the therapeutic concentration within 10‐15 min. In terms of Sublingual glands permeability, the sublingual area of the oral cavity Salivary glands which are present in the floor of the is more permeable than the buccal () area, mouth underneath the tongue. They are also known which in turn is more permeable than the palatal as sublingual glands. They produce mucin in turn (roof of the mouth) area. The differences in produces saliva. The interior area of the mouth permeability are generally based on the relative remains lubricated due to production of the saliva thickness, the blood supply, and degree of by the glands, which is necessary for chewing and keratinization of these membranes. In addition to food swallowing. The fluid which is produced by the differences in the permeability of the various the glands gets mix with the food, so the food gets mucous membranes, the extent of drug delivery is easily chewed. Due to low secretion of the saliva it

Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 914 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 can create problem in swallowing the food and vasodilator substances are produced, and the potential for food lodge in the throat increases. glandular blood flow increases, due to increased The absorption is transfer of the drug from its site glandular metabolism. of administration into systemic circulation, so it The sublingual travels forward to the can be said that absorption is directly proportional sublingual gland, it supplies the gland and branches layer thickness. The absorption of the drug follows to the neighboring muscles and to the mucous in this way Sublingual > Buccal > Gingival > membranes of the mouth, tongue and gums. Two Palatal. Due to high permeability and rich blood symmetrical branches travel behind the jaw supply, the sublingual route can produce rapid under the tongue to meet and join at its tip. Another onset of action so the drug with short delivery branches meets and anastomoses with the sub period can be delivered and regimen is mental branches of the facial artery. The sublingual frequent. The drug gets diluted in the saliva and artery system stems from the lingual artery – the from there the drug is adsorbed across the oral body’s main blood supply to the tongue and the cavity. floor of the mouth – which arises from the external For example: Glyceryl nitrate-a potent coronary carotid artery. The proximity with the internal vasodilator which is used for rapid symptomatic carotid artery allows fast access to its route relief of . After administration its gets supplying the greater part of the cerebral pharmacologically active after 1-2 minutes. Oral hemisphere spray was found to provide rapid relief of symptom with first class metabolism. The extent of Drugs for sublingual administration first class metabolism when compared to the Sublingual drug administration is applied in the sublingual spray decreased to 48% with sublingual field of cardiovascular drugs, steroids, some tablets and 28% with the oral dose. Nitrate which barbiturates and enzymes. It has been a developing appears in the plasma concentration can be field in the administration of many vitamins and maintained for 24 hours when administrated which are found to be readily and sublingually9. thoroughly absorbed by this method. Sublingually absorbed nutrition, which avoids exposure to the The Mechanism of Sublingual Absorption gastric system and liver, means direct nutritional The absorption potential of the buccal mucosa is benefits, particularly important for sufferers of influenced by the lipid and therefore the gastro‐intestinal difficulties such as ulcers, permeability of the (osmosis), the hyperactive gut, coeliac disease, those with ionization (pH), and the molecular weight of the compromised digestion, the elderly and invalids – substances. For example, absorption of some drugs the nutritional benefit is independent of via the buccal mucosa is shown to increase when gastro‐intestinal influences(10,11). Examples of drugs carrier pH is lowering (more acidic) and decrease administered by this route include antianginal like with a lowering of pH (more alkaline). The cells of nitrites and nitrates, anti hypertensive like the oral epithelium and are also capable , like and of absorbing by endocytosis (the uptake of particles bronchodilators like fenoterol. Certain steroids like by a as if by hollowly wrapping itself around it. and peptides like can also be These engulfed particles are usually too large to administered e.g. citrate, apomorphine, diffuse through its wall). It is unlikely that this prochlorperazine dimaleate {PRO}, and hydrazine mechanism is used across the entire stratified HCl {HYD}. epithelium. It is also unlikely that active transport processes operate within the oral mucosa. However, it is believed that acidic stimulation and Sublingual formulation uptake into the . Sublingual tablets The mouth is lined with a They are to be placed under the tongue and produce which is covered with squamous epithelium and immediate systemic effect by enabling the drug contains mucous glands. The buccal mucosa is absorbed directly through mucosal lining of the similar to the sublingual mucosal . mouth beneath the tongue. The drug absorbed from The salivary glands consist of lobules of cells stomach goes to mesenteric circulation which which secrete saliva through the salivary ducts into connects to stomach via portal vein. Thus the mouth. The three pairs of salivary glands are absorption through oral cavity avoids first pass the Parotid, the Sub mandibular and the Sublingual metabolism. The tablets are usually small and flat, which lies on the floor of the mouth. The more acid compressed lightly to keep them soft. The tablet the the greater the stimulation of salivary must dissolve quickly allowing the API to be output, serving also to avoid potential harm to acid absorbed quickly. It is designed to dissolve in small sensitive tooth enamel by bathing the mouth in quantity of saliva. After the tablet is placed in the copious neutralizing fluid. With stimulation of mouth below the tongue, the patient should avoid salivary secretion oxygen is consumed and eating, drinking, smoking and possibly talking in

Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 915 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 order to keep the tablet in place. Swallowing of (in which quick onset of action is necessary) to saliva should also be avoided since the saliva may mental illness (in which patient compliance is contain dissolved drug. Bland are used necessary for treating chronic indications such as to avoid salivary stimulation. Various techniques mental depression and schizophrenia)(23). can be used to formulate rapidly disintegrating or (12,13) dissolving tablets. Direct compression is one of these techniques which require incorporation of a superdisintegrant into the formulation, or the use of highly water-soluble excipients to achieve fast tablet disintegration. Direct compression does not require the use of water or heat during the formulation procedure and is the ideal method for moisture and heat-labile . a) Fast disintegrating sublingual tablets (FDT) FDT is defined as a solid dosage form that contains medicinal substances and disintegrates rapidly (within few seconds) without water when kept on the tongue. The drug is released, dissolved, or dispersed in the saliva, and then swallowed and absorbed across the GIT (14). FDTs also are also called as Orodispersible tablet, mouth-dissolving, quick-dissolving, fast-melt, and freeze-dried wafers. Tablets that disintegrate or dissolve rapidly in the patient’s mouth are convenient for young children, the elderly and patients with swallowing b) sublingual tablets difficulties and in situations where potable The new sublingual tablet concept presented is are not available. Direct compression is one of the based on interactive mixtures consisting of a water techniques which require the incorporation of a soluble carrier covered with fine drug particles and superdisintegrant into the formulation, or the use of a bioadhesive component. With this approach, it is highly water soluble excipients to achieve fast possible to maintain rapid dissolution in tablet disintegration. Compared to conventional combination with bioadhesive retention of the drug dosage form the drug dissolution, its absorption as in the oral cavity. Bioadhesion is usually defined as well as onset of clinical action and its the bond formed between two biological surfaces bioavailability may be significantly greater(15-17). or between a biological and a synthetic surface. Though chewable tablets are available in the Problem associated with sublingual tablet market, they are not same as the new FDTs. formulation is that there is always a risk that the Patients for whom chewing is difficult or painful patient will swallow part of the dose before the can use these FDTs. It can be used easily in infants active substance has been released and absorbed and in children who have lost their primary teeth locally into systemic circulation. this could results and who do not have full use of their permanent an unwanted prolongation of the pharmacological teeth(18). effect. Addition of a bioadhesive component is a Recent market studies indicate that more than half well-known method of increasing the possibility of of the patients prefers FDTs than other a more site-specific release. However, this concept conventional dosage forms(19) and most patients is normally applied to non-disintegrating tablets or would ask their doctors for FDTs (70%), purchase disc to achieve extended release of the active FDTs (70%), or prefer FDTs than regular tablets or substance and, consequently, such a system will not liquids (>80%)(20). The US Food and Drug be suitable for a fast acting formulation. Therefore, Administration Center for Drug Evaluation and it would be of interest to study a disintegrating Research (CDER) defines, in the „Orange Book, tablet which releases the drug quickly, but which an FDT as “a solid dosage form containing also has bioadhesive properties which could medicinal substances, which disintegrates rapidly prevent the drug from being swallowed. in saliva, usually within a few seconds, when placed upon the tongue”(21). The implication of Bioadhesion mechanisms these dosage forms is emphasized by the term The layer is often involved in the adhesion “Orodispersible Tablet”, by the European of a bioadhesive and is present as either a Pharmacopoeia which defines it as a tablet that can layer adhering to the mucosal surface or a be placed in oral cavity where it disperses rapidly solution or suspension of various substances. The before swallowing(22). FDTs has been developed mucus layer mainly consists of mucin , for numerous indications ranging from migraines

Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 916 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 inorganic salts, , lipids and water with the the cheek. Thin film’s ability to dissolve rapidly composition varying depending on its source. The without the need for water provides an alternative electronic theory involves an electronic transfer to patients with swallowing disorders and to between the two materials causing a double layer patients suffering from nausea, such as those of electric charge, which results in attraction forces. patients receiving . The adsorption theory involves adhesion between The first developed fast-dissolving dosage form the mucosa and the material by van der consisted in tablet form, and the rapid waals interaction, hydrogen bonds and related disintegrating properties were obtained through a forces. The wetting theory involves interfacial special process or formulation modifications24. tensions between the two materials. Penetration of More recently, fast-dissolving films are gaining the polymer chains into the mucus network and interest as an alternative to fast-dissolving tablets to vice versa, causing a mechanical bond, is referred definitely eliminate patients’ fear of chocking and to as the diffusion theory. The importance of water overcome patent impediments. Fast-dissolving content and movement of water into the adhesive films are generally constituted of plasticized material from the mucosa, i.e. dehydration of the hydrocolloids. Problems are caused by foaming mucosa, has also been suggested as a mechanical during the film formation due to the heating of the for adhesion. material or solvent evaporation, the flaking during the slitting and the cracking in the cutting phase. Measurement of bio-adhesive strength The films should be stable to moisture, facilitate Bio-adhesion strength of the tablets was measured the handling, have to be flexible and exhibit a on a modified physical balance. The method used suitable tensile stress and do not stick to the bovine cheek pouch as the method mucosal and packaging materials and fingers. IPB ph 6.6 as the moistening fluid. The surface of Film can be prepared by five method: 1) Solvent the mucosal membrane was first blotted with a casting. 2)Semisolid casting. 3)Hot melt extrusion. filter paper and then moistened with 25/L 1 of IPB 4)Solid dispersion extrusion. 5) Rolling. pH 6.6. the weight in grams is required to detach the tablets from the mucosal surface gave the 1) Solvent casting method measure of bio-adhesive strength. Film is formulated using the solvent casting method, whereby the water-soluble ingredients are c) Lipid matrix sublingual tablets dissolved to form a clear viscous solution. The API Such tablets are formulated using advances in and other agents are dissolved in smaller amounts sublingual and liposomal technology to create a of the solution and combined with the bulk. This dosage form that offers a faster and more complete mixture is then added to the aqueous viscous absorption than traditional oral routes of solution. The entrapped air is removed by vacuum. administration. The lipid matrix sublingual tablet is The resulting solution is cast as a film and allowed a bioavailable, quick, convenient and consistent to dry, which is then cut into pieces of the desired dosage form for many neutraceuticals that are often size.25 taken orally. 2)Semisolid casting For e.g., Glutathione MB12(methylcobalamin) Solution of water soluble film forming polymer is melatonin. mixed with solution of acid insoluble polymer which forms homogenous viscous solution. The d) Sublingual vitamin tablet ratio should be 1:4. For e.g. cellulose acetate Vitamin D i.e. cholecalciferol is a natural precursor phthalate, cellulose acetate butyrate. It is then of calcium regulating hormone calcitriol. Vitamin sonicated which is coated on non-treated casting D is thus used in hypocalcaemia/ film. hyperparathyroidism. Because of its incomplete 3)Hot Melt Extrusion absorption from GI tract, local intestinal In present method the mass is prepared first under degradation and hepatic metabolism, it is given the control of temperature and steering speed. sublingually. Afterwards, the film is coated and dried in a drying tunnel, once again the temperature, air circulation 2)Thin film drug delivery and line speed are controlled. Then follows a Thin film drug delivery is a process of delivering slitting and in the last step the films are punched, drugs of the systemic circulation via thin film that pouched and sealed.26 dissolves when in contact with liquid, often 4)Solid Dispersion Extrusion referred to a dissolving films or strips and dissolve Solid dispersions are prepared by immiscible within 1 min when placed in the mouth without components and drug. Finally the solid dispersions drinking or chewing. are shaped in to films by means of dies. Such dissolving film or strip are typically designed 5)Rolling for , with the user placing the Solution or suspension drug is rolled on the carrier. strip on or under the tongue or along the inside of The solvent is mainly water and mixture of water

Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 917 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 and . The film is dried on the rollers and sublingual tablets, the disintegration apparatus for gives desired shape and size27. oral tablets is used without the covering disks,29 and 2 minutes is specified as the acceptable Evaluation time limit for tablet disintegration[29].. Hardness and thickness The test is done as per the standard methods. The Water absorption ratio hardness of three randomly selected tablets from A piece of tissue paper folded twice is placed in a each formulation is determined by placing each small Petri dish Containing 6 ml of water. A tablet tablet diagonally between the two plungers of tablet is put on the tissue paper and allowed to completely hardness tester (with the nozzle) and applying wet. The wetted tablet is then weighted. Water pressure until the tablet broke down into two parts absorption ratio, R was determined using following completely and the reading on the scale is noted equation28. down(28).The thickness of three randomly selected tablets from each formulation is determined in mm R = 100 × Wa –Wb/Wa using a vernier caliper (Pico India). The average values is calculated28. where, Wa = Weight of tablet after water absorption Drug Content Wb = Weight of tablet before water absorption. Randomly ten tablets are selected from formulation, finely powdered and In vitro disintegrating test equivalent mg of drug is accurately weighed and Disintegration times for sublingual tablets is transferred to 100 ml volumetric flasks containing determined using USP tablet disintegration solution of desired pH. The flask is shaken to mix apparatus with desired medium. The volume of the contents thoroughly. The volume is made up to medium was 900 ml and temp was 37± 2 °C. The the mark with solution and filtered. One ml of the time in seconds taken for complete disintegration filtrate is suitably diluted and drug content is of the tablets with no palatable mass remaining in estimated using a double beam UV-visible the apparatus is measured28. spectrophotometer. This procedure is repeated thrice and the average value is calculated. In vitro dissolution test In-vitro release rate of sublingual tablets will be Wetting time (WT) carried out using United State Pharmacopoeia It is useful for quality control and provides (USP) XXIV dissolution testing apparatus (Paddle supportive evaluation of these sublingual tablets. method). A aliquot sample of the solution is Unlike the disintegration test, the wetting test uses withdrawn from the dissolution apparatus. The minimal water, which may be more representative samples are replaced with fresh dissolution of the quantity of moisture available sublingually. medium of same quantity. The samples are filtered Using this test, the time required for moisture to through Whatman filter paper No 40 and analyzed penetrate the tablet completely is measured and in UV spectrophotometer. The percentage drug possibly represents the time required to release release is calculated using an equation obtained drug in the presence of minute volumes of saliva from the calibration curve30. The tablet was placed above absorbent paper fitted into a petri dish. After the paper is thoroughly Test for film wetted with distilled water, excess water is Tensile Strength completely drained out of the dish. The time Tensile strength is the maximum stress applied to a required for the water to diffuse from the wetted point at which the film specimen breaks31. It is absorbent paper throughout the entire tablet is then calculated by the applied load at rupture divided by recorded using a stopwatch28 the cross-sectional area of the film as given below:

Disintegration test Tensile strength = Load at failure × 100 A relatively simple method with rigorous Film thickness × film width conditions is developed. Each individual tablet is dropped into 10‐ml glass test tube (1.5‐cm Percent Elongation diameter) containing 2ml distilled water, and the A film sample stretches when stress is applied and time required for complete tablet disintegration is it is referred to as strain. Strain is basically the observed visually and recorded using a stopwatch. deformation of film divided by original dimension The visual inspection is enhanced by gently of the sample. Elongation of film increases as the rotating the test tube at a 450 angle, without plasticizer content increases. agitation, to distribute any tablet particles that might mask any remaining undisintegrated portion of the tablets. In the USP disintegration test for

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Percent Elongation withdrawn from the solution and diluted to 10mL. The absorbance of the solution was taken at 276 -L * 100 nm and concentration was calculated. By correcting Lo dilution factor, the drug content was calculated. where, The test was performed in triplicate35. L = Increase in length of film Lo = Initial length of film. In-vitro dissolution studies Dissolution study was carried out in USP paddle Young's Modulus type apparatus using 300 mL of stimulated salivary Young's modulus or elastic modulus is the measure fluid (pH 6.8) as a dissolution medium at 50 rpm. of stiffness of film. It is represented as the ratio of Temperature of the dissolution medium was applied stress over strain in the region of elastic maintained at 37±0.5ºC. Samples of 5ml were deformation as follows: withdrawn at every 4 minute interval, filtered Young's Modulus = Slope * 100 (through 0.45µ) and replaced with 5ml of fresh Film thickness * dissolution medium. The samples were suitably Cross-head speed diluted and estimated spectrophotometrically at 276 nm by using ELICO-164 double beam UV-Visible Folding Endurance spectrophotometer. The dissolution experiments Folding endurance is determined by drying process were conducted in triplicate. Dissolution rate was repeated folding of the film at the same place till studied for all designed formulations and the breaks. The number of times the film is folded dissolution parameters were calculated. without dry breaking is computed as the folding endurance value 32. CONCLUSION Sublingual drug delivery have been used for formulation of many drugs with view point of rapid Thickness drug release and quick onset of action. Sublingual The thickness of the polymer films was measured products were developed to overcome the difficulty by using screw gauge. The thickness of each strip in swallowing conventional tablet, among pediatric, at six different areas was determined and standard geriatric and psychiatric patients with dysphagia. deviation was calculated 33 The target population has expanded to those who want convenient dosing without water anywhere, In vitro disintegration time anytime. The potential for such dosage forms is In vitro disintegration time is determined visually promising because strong market acceptance and in a glass dish of 25ml distilled water with swirling patient demand. Peak blood levels of most products every 10 sec. The disintegration time is the time administered sublingually are achieved within when the film starts to break or disintegrates. The 10‐15 minutes, which is generally much faster than disintegration time of prepared films was measured when those same drugs are ingested orally. in triplicate34. Sublingual absorption is efficient. The percent of each dose absorbed is generally higher than that Uniformity of drug content achieved by means of oral ingestion. Various types The film of area 1x1 cm2 was cut and dissolved in of sublingual dosage forms are available in market 6.8 phosphate buffer solution and made up to 100 like tablets, films and sprays. mL in a volumetric flask. Then 1 mL was

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Table 1: Superdisintegrant Commercially available Mechanism Special comment 0f action Cross linked Crosscarmellose® Swells 4-8 folds Swells in two Cellulose Ac-Di-Sol®, in < 10 dimensions. Nymce ZSX® seconds. Direct Primellose®, Swelling and compression Solutab®, wicking both or Granulation Vivasol®, L-HPC free. Cross linked PVP Crosspovidone M® Swells very little Water Kollidon® and returns insoluble and Polyplasdone® to original size spongy in after nature so get compression but porous tablet act by action Crosslinked starch Explotab® Swells 7-12 folds Swells in three Primogel® in < 30 dimensions seconds. and high level serve as sustain release matrix Crosslinked alginic Alginic acid NF Rapid swelling in Promote Acid aqueous disintegration medium or in both dry wicking action or wet granulation.

Table 2: Marketed Products of Sublingual Tablet Brand Name Catergory Srength 50, 100, 200, 300, 400, 600, Abstral Fentanyl Citrate Opioid 800 µg Subutex Opioid Analgesic 2 and 8mg Avitan Lorazepam Antianxiety 1, 2 mg Edular tartrate Sedatives/ Hypnotics 5, 10 mg Isordil Isosorbide dinitrate Vasodilators 2.5, 5 10mg Suboxone Buprenorphine Narcotic + Opioid antagonist 2/0.5, 8/2 mg hydrochloride Nitrostat Nitroglycerine Antianginal 0.3 mg , 0.4 mg , or 0.6 mg

Fig. 1:

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Fig. 2: Diagram of sublingual gland and sublingual artery

Fig. 3: Thin Film Drug Delivery

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