International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 __________________________________________Review Article An Overview on: Sublingual Route for Systemic Drug Delivery K. Patel Nibha1 and SS. Pancholi2* 1Department of Pharmaceutics, BITS Institute of Pharmacy, Gujarat Technological university, Varnama, Vadodara, Gujarat, India 2BITS Institute of Pharmacy, Gujarat Technological University, Varnama, Vadodara, Gujarat, India. __________________________________________________________________________________ ABSTRACT Oral mucosal drug delivery is an alternative and promising method of systemic drug delivery which offers several advantages. Sublingual literally meaning is ''under the tongue'', administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. Sublingual route offers advantages such as bypasses hepatic first pass metabolic process which gives better bioavailability, rapid onset of action, 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 drugs, 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 stomach 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 route of administration. 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 metabolism, 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 gastrointestinal tract 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 solid dosage form. 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 liquid orals. But the liquid orals (syrup, physicochemical properties of the drug1. suspension, emulsion 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, Vol. 3 (2) Apr – Jun2012 www.ijrpbsonline.com 913 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 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 schizophrenia.)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 cheeks and the area between to swallow a tablet, such as pediatric, geriatric the gums 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, • Water is not required for swallowing the delivery for the local treatment of ulcers, bacterial dosage form, which is convenient feature for and fungal infections 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 medication 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 absorption the reticulated vein which lies underneath the oral which will leads to rapid, onset of action. mucosa, and transported through the facial veins, • 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 injection. For these Since sublingual administration of drugs formulations, the small volume of saliva is usually interferes with eating, 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 smoking causes short biological half life (3‐5 min.), however the vasoconstriction 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 (cheek) 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