System 120 SEMINAR ON Sublingual Drug Delivery 1

System 1/20 SEMINAR ON Sublingual Drug Delivery

1. Anatomy physiology of mucosa 2. Sublingual tablets 3. Fast-disintegrating sublingual tablets 4. Bioadhesive sublingual tablet 5. Thin film drug delivery 6. Lipid matrix sublingual tablet 7. Sublingual immunotherapy 8. Sublingual vitamin tablet 9. Market preparation 10. PATENTS 11. References 2/20 List of contents

1: Anatomy and Physiology of mucosa • Thickness of mucosa: 100 -200 micrometer • Epithelium: Non keratinized • Composition: Neutral but polar lipid eg. Cholesterol sulfate, Glucosyl ceramide • Composition of saliva: 99. 5 % water, Proteins, Glycoprotein, High K (7 X Plasma), Bicarbonate( 3 X plasma), Calcium, Phosphorous, Chloride, Low sodium(1/10 X Plasma) 3/20 • Sublingular gland: 5% saliva • p. H : 5. 6 -7. 0

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Mechanism of transportation Highly vascular mucosal lining Sublingual capillaries and veins Jugular veins Superior Vena cava 5/20 Arterial Circulation

v Sublingual tablets v. They are to be placed under the tongue and produce immediate systemic effect by enabling the drug absorbed directly through mucosal lining of the mouth beneath the tongue. 6/20 v. The drug absorbed from stomach goes to mesenteric circulation which connects to stomach via portal vein. Thus, absorption through oral cavity avoids first-pass metabolism

v. The tablets are usually small and flat, compressed lightly to keep them soft. The tablet must dissolve quickly allowing the API to be absorbed quickly. It’s designed to dissolve in small quantity of saliva. After the tablet is placed in the mouth below the tongue, the patient should avoid eating, drinking, smoking and possibly talking in order to keep the tablet in place. 7/20 v. Swallowing of saliva should also be avoided since the saliva may contain dissolved drug. Bland excipients are used to avoid salivary stimulation.

Advantages 1) Rapid absorption 8/20 2) Dose reduction 3) Fast on set of action 4) Increase B. A. 5) Reduction in side effects 6) Suitable in disease like nausea, vomitting 7) Not required water

Disadvantage 9/20 1) High dose can not be administered 2) Less area is available for absorption 3) Not suitable for bitter and irritating drugs 4) Less patient compliance 5) No eating, Drinking and smoking is allowed 6) Highly ionic drugs can not be administered

Suitability of API for preparation of sublingual tablet • Many drug properties could potentially affect the performance of sublingual tablets. For example, the solubility, crystal morphology, particle size, hygroscopicity, compressibility and bulk density of a drug can significantly affect the final tablet’s characteristics, such as tablet strength and disintegration. • Drugs that are unstable in parenteral preparation are suitable for sublingual dosage form. 10/20 • Some drugs undergoes extensive first pass metabolism which results in poor bioavailability of its oral dosage forms that kind of drugs are suitable for sublingual dosage form.

• Surface p. H of the tablet • Uniformity of weight • Content uniformity • Hardness • Thickness • Diameter • Disintegration time • Wetting time and • Friability Wetting Time (WT): The tablet was placed at the center of 2 layers of absorbent paper fitted into a rectangular plastic dish (11 cm × 7. 5 cm). After the paper was thoroughly wetted with distilled water, excess water was completely drained out of the dish. The time required for the water to diffuse from the wetted absorbent paper throughout the entire tablet was then recorded using a stopwatch 11/20 Evaluation

3. Fast-disintegrating sublingual tablets 12/20 • Tablets that disintegrate or dissolve rapidly in the patient’s mouth are convenient for young children, the elderly and patients with swallowing difficulties, and in situations where potable liquids are not available.

4. Bioadhesive sublingual tablet 13/20 v The new sublingual tablet concept presented is based on interactive mixtures consisting of a water-soluble carrier covered with fine drug particles and a bioadhesive component. With this approach, it is possible to obtain rapid dissolution in combination with bioadhesive retention of the drug in the oral cavity.

5. Thin film drug delivery 14/20 Thin film drug delivery is a process of delivering drugs to the systemic circulation via a thin film that dissolves when in contact with liquid, often referred to as a dissolving film or strip. thin film strips are typically designed for oral administran, with the user placing the strip on or under the tongue or along the inside of the cheek. As the strip dissolves, the drug can enter the blood stream enterically buccally or sublingually. The sublingual delivery of a drug via thin film has the potential to improve the onset of action, lower the dosing, and enhance the efficacy and safety profile of the medicament.

6. Lipid matrix sublingual tablet • Lipid Matrix Sublingual Tablet is formulated using advances in sublingual and liposomal technology to create a dosage form that offers a faster and more complete absorption than traditional oral routes of administration. • The Lipid Matrix Sublingual Tablet is a bioavailable, quick, convenient, and consistent dosage form for many specialty nutraceuticals that are often taken orally. 15/20 Examples Include: Glutathione MB 12 (Methylcobalamin) Melatonin A True Sublingual Tablet + Lipid Matrix Technology: • Not a Lozenge, Troche, or Tablet Triturate: A True Sublingual Tablet! • Rapid Dissolve Formula • Liposomal Drug Delivery • Bioavailable & Avoids First Pass Effect • Convenient & Consistent Dosing Application • Single or Combination Drug Delivery

7. Sublingual immunotherapy, or SLIT, is a form of immunotherapy that involves putting drops of allergen extracts under the tongue. SLIT is usually delivered one of two ways: drops (or tablets) of allergen extract are placed under the tongue, then either swallowed or spat out. 8. Sublingual vitamin tablet 16/20 The only Sublingual vitamin that all doctors recommend is vitamin B 12 (Cyanocobalamin). you must have enough of it for your bodies metabolism. Recommended to be taken once a day.

9. Market preparation • Tenormin sublingual tablet (isoproterenol) • Microtab sublingual tablet (nicotine) • Nascobal sublingual tablet (vitamin B 12) • Subuter sublingual tablet (buprenorphine) 17/20 • Nitroquick sublingual tablet (nitroglycerin)

10. PATENTS 4539315 4927816 4988683 5320848 5629022 5683721 6183775 6447754 SUBJECT Sublingually absorbable nontoxic aspirin composition Formulae and methods for sublingual ingestion of natural progesterone New pharmaceutical compositions for the buccal tract and process for their preparation Chewable drug-delivery composition Method for galenically preparing a therapeutic composition based on aspirin Galenic preparation of therapeutic composition comprising aspirin Buccal delivery system Oral rinse methods and compositions YEAR 1985 1990 1991 1994 1997 2001 2002 18/20 US PATENT NO.

REFERENCE 1. Hariharan, Madhu; Bogue, B. Arlie (February 2009). "Orally Dissolving Film Strips (ODFS): The Final Evolution of Orally Dissolving Dosage Forms". Drug Delivery Technology (Montville, New Jersey) 9 (2): 24 -29. ISSN 1537 -2898. OCLC 48060225. http: //www. drugdeliverytechonline. com/drugdelivery/200902/? pg=24. 2. "Oral Thin Films, " in Orally Disintegrating Tablet and Film Technologies, 5 th ed. (Technology Catalysts International, Falls Church, VA, 2008) 3. "S. S. Biradar, S. T. Bhagavati, I. J. Kuppasad: Fast Dissolving Drug Delivery Systems: A Brief Overview. The Internet Journal of Pharmacology. 2006. Volume 4 Number 2". 4. "Thin Film Manufacturing Process Patent". http: //www. monosolrx. com/news_08/news_41508. html. Retrieved 2009 -09 -21 Monosolrx. com. 5. Mathiowitz, E. , Chickering, D. E. , Lehr, C. M. (eds. ), Bioadhesive drug delivery systems: Fundamentals, novel approaches and development. Marcel Dekker Inc, New York, USA, pp. 1 -10. 6. Duchêne, D. , Touchard, F. , Peppas, N. A. , 1988. Pharmaceutical and medical aspects of bioadhesive systems for drug administration. Drug Dev. Ind. Pharm. , 14, 283 -318. 8. D. Harris and J. R. Robinson, Drug delivery via the mucous membranes of the oral cavity, J. Pharm. Sci. 81 (1992) 1– 10; DOI: 10. 1002/jps. 2600810102. 9. www. pharmainfo. net 10. www. pubmed. com 19/20 7. Mahrag Tur, K. , Ch’ng, H. -S. , 1998. Evaluation of possible mechanim(s) of bioadhesion. Int. J. Pharm. , 160, 61 -74.

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